Deborah Kado

All Publications

• Neighborhood Socioeconomic Deprivation and Health Care Costs in Older Community-Dwelling Adults: Importance of Functional Impairment and Frailty. Journal of general internal medicine Schousboe, J. T., Langsetmo, L., Kats, A. M., Taylor, B. C., Boyd, C., Van Riper, D., Kado, D. M., Duan-Porter, W., Cawthon, P. M., Ensrud, K. E. 2024

  Abstract

  Low neighborhood socioeconomic status is associated with adverse health outcomes, but its association with health care costs in older adults is uncertain.To estimate the association of neighborhood Area Deprivation Index (ADI) with total, inpatient, outpatient, skilled nursing facility (SNF), and home health care (HHC) costs among older community-dwelling Medicare beneficiaries, and determine whether these associations are explained by multimorbidity, phenotypic frailty, or functional impairments.Four prospective cohort studies linked with each other and with Medicare claims.In total, 8165 community-dwelling fee-for-service beneficiaries (mean age 79.2 years, 52.9% female).ADI of participant residence census tract, Hierarchical Conditions Category multimorbidity score, self-reported functional impairments (difficulty performing four activities of daily living), and frailty phenotype. Total, inpatient, outpatient, post-acute SNF, and HHC costs (US 2020 dollars) for 36 months after the index examination.Mean incremental annualized total health care costs adjusted for age, race/ethnicity, and sex increased with ADI ($3317 [95% CI 1274 to 5360] for the most deprived vs least deprived ADI quintile, and overall p-value for ADI variable 0.009). The incremental cost for the most deprived vs least deprived ADI quintile was increasingly attenuated after separate adjustment for multimorbidity ($2407 [95% CI 416 to 4398], overall ADI p-value 0.066), frailty phenotype ($1962 [95% CI 11 to 3913], overall ADI p-value 0.22), or functional impairments ($1246 [95% CI -706 to 3198], overall ADI p-value 0.29).Total health care costs are higher for older community-dwelling Medicare beneficiaries residing in the most socioeconomically deprived areas compared to the least deprived areas. This association was not significant after accounting for the higher prevalence of phenotypic frailty and functional impairments among residents of socioeconomically deprived neighborhoods.

  View details for DOI 10.1007/s11606-024-08875-8

  View details for PubMedID 38937364

  View details for PubMedCentralID 5126022

• Hip Fracture Risk Assessment Tools for Adults Aged 80 Years and Older. JAMA network open Ensrud, K. E., Schousboe, J. T., Crandall, C. J., Leslie, W. D., Fink, H. A., Cawthon, P. M., Kado, D. M., Lane, N. E., Cauley, J. A., Langsetmo, L. 2024; 7 (6): e2418612

  Abstract

  While adults aged 80 years and older account for 70% of hip fractures in the US, performance of fracture risk assessment tools in this population is uncertain.To compare performance of the Fracture Risk Assessment Tool (FRAX), Garvan Fracture Risk Calculator, and femoral neck bone mineral density (FNBMD) alone in 5-year hip fracture prediction.Prognostic analysis of 3 prospective cohort studies including participants attending an index examination (1997 to 2016) at age 80 years or older. Data were analyzed from March 2023 to April 2024.Participants contacted every 4 or 6 months after index examination to ascertain incident hip fractures and vital status. Predicted 5-year hip fracture probabilities calculated using FRAX and Garvan models incorporating FNBMD and FNBMD alone. Model discrimination assessed by area under receiver operating characteristic curve (AUC). Model calibration assessed by comparing observed vs predicted hip fracture probabilities within predicted risk quintiles.A total of 8890 participants were included, with a mean (SD) age at index examination of 82.6 (2.7) years; 4906 participants (55.2%) were women, 866 (9.7%) were Black, 7836 (88.1%) were White, and 188 (2.1%) were other races and ethnicities. During 5-year follow-up, 321 women (6.5%) and 123 men (3.1%) experienced a hip fracture; 818 women (16.7%) and 921 men (23.1%) died before hip fracture. Among women, AUC was 0.69 (95% CI, 0.67-0.72) for FRAX, 0.69 (95% CI, 0.66-0.72) for Garvan, and 0.72 (95% CI, 0.69-0.75) for FNBMD alone (FNBMD superior to FRAX, P = .01; and Garvan, P = .01). Among men, AUC was 0.71 (95% CI, 0.66-0.75) for FRAX, 0.76 (95% CI, 0.72-0.81) for Garvan, and 0.77 (95% CI, 0.72-0.81) for FNBMD alone (P < .001 Garvan and FNBMD alone superior to FRAX). Among both sexes, Garvan greatly overestimated hip fracture risk among individuals in upper quintiles of predicted risk, while FRAX modestly underestimated risk among those in intermediate quintiles of predicted risk.In this prognostic study of adults aged 80 years and older, FRAX and Garvan tools incorporating FNBMD compared with FNBMD alone did not improve 5-year hip fracture discrimination. FRAX modestly underpredicted observed hip fracture probability in intermediate-risk individuals. Garvan markedly overpredicted observed hip fracture probability in high-risk individuals. Until better prediction tools are available, clinicians should prioritize consideration of hip BMD, life expectancy, and patient preferences in decision-making regarding drug treatment initiation for hip fracture prevention in late-life adults.

  View details for DOI 10.1001/jamanetworkopen.2024.18612

  View details for PubMedID 38941095

• Difference between kidney function by cystatin C versus creatinine and association with muscle mass and frailty. Journal of the American Geriatrics Society Yuan, J. H., Rifkin, D. E., Ginsberg, C., Cawthon, P. M., Kado, D. M., Bauer, S. R., Ensrud, K. E., Hoffman, A. R., Potok, O. A. 2024

  Abstract

  A higher difference in estimated glomerular filtration rate by cystatin C versus creatinine (eGFRDiff = eGFRCys - eGFRCreat) is associated with decreased frailty risk. Since eGFRCreat is influenced by muscle more than eGFRCys, muscle mass may explain this association. Previous work could not account for this when considering regional muscle measures by imaging. Deuterated creatine (D3Cr) dilution measures whole body muscle mass (kilograms). We aimed to determine whether eGFRDiff is associated with D3Cr muscle mass and whether muscle mass explains the association between eGFRDiff and frailty.Cross-sectional analysis within the multicenter MrOS Study at Year 14 (visit 4). 490 men of the original cohort of 5994 MrOS participants (aged ≥65 at enrollment) were included. Exposure was eGFRDiff (= eGFRCys - eGFRCreat), calculated using CKD-EPI equations 2012/2021. Primary outcome was D3Cr muscle mass. Secondary outcome was phenotypic pre-frailty (one or two criteria) and frailty (≥three criteria) including the following: weight loss, weakness, slow gait, physical activity, poor energy. The association of eGFRDiff with D3Cr muscle mass was examined by linear regression, that with prefrailty / frailty by multinomial logistic regression.Mean ± SD age was 84 ± 4 years, eGFRCreat 68 ± 16, eGFRCys 52 ± 16, eGFRDiff -15 ± 12 mL/min/1.73 m2 and D3Cr muscle mass 24 ± 4 kg. For each SD increment in eGFRDiff, D3Cr muscle mass was 1.4 kg higher on average, p < 0.0001 (fully adjusted). Higher eGFRDiff was associated with lower odds of frailty (OR = 0.63 95% CI [0.45;0.89]), but this was partially attenuated and insignificant after additionally adjusting for D3Cr muscle mass (OR = 0.85 95% CI [0.58; 1.24]).Higher eGFRDiff is associated with lower odds of frailty among late-life men. D3Cr muscle mass accounts for some of this association. This suggests that non-GFR determinants of creatinine and cystatin C, such as muscle mass, play a role in explaining the association of eGFRDiff with frailty. Future studies are needed to confirm.

  View details for DOI 10.1111/jgs.19014

  View details for PubMedID 38819605

• Replacing sedentary time for physical activity: Does intensity matter for body composition in oldest-old adults? Journal of sports sciences Hetherington-Rauth, M., Webber, K., Roe, L. S., Hoffman, A. R., Kado, D., Langsetmo, L., Orwoll, E. S., Cawthon, P. 2024: 1-10

  Abstract

  To assess the independent and combined relationships among objectively measured sedentary time (ST), light intensity PA (LPA), and moderate-to-vigorous intensity PA (MVPA) with muscle mass and fat mass (FM) and how theoretical displacement of these inter-dependent behaviours relates to body composition in oldest-old men. A total of 1046 men participating in the year 14 visit of the prospective Osteoporotic Fractures in Men (MrOS) cohort study with complete data for accelerometry, dual x-ray absorptiometry, and deuterated creatine dilution (D3Cr) muscle mass were included in the analysis (84.0 ± 3.8 yrs.). Single, partition, and isotemporal substitution models were used to assess the interrelationships between PA intensities and ST with body composition measures, while controlling for relevant confounders. Replacing 30-min of ST with 30-min of MVPA was associated with lower FM (β =-0.17, p < 0.001) and higher D3Cr muscle mass, although this was of borderline significance (β = 0.07, p = 0.05). Replacing 30-min of ST for LPA was associated with lower FM (β =-0.15, p < 0.001), but there was no effect on D3Cr muscle mass (p > 0.05). Exchanging ST with any intensity of PA is associated with benefits for FM in oldest-old adult men, although substitution with MVPA may be more beneficial than LPA for maintaining/improving skeletal muscle mass.

  View details for DOI 10.1080/02640414.2024.2348911

  View details for PubMedID 38696674

• Balancing fracture risk versus risk of mortality before fracture among women aged 80 years or older. Journal of the American Geriatrics Society Schousboe, J. T., Langsetmo, L., Fink, H. A., Kado, D. M., Cauley, J. A., Taylor, B. C., Ensrud, K. E. 2024

  Abstract

  Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non-spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks.Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow-up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture.Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self-rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5-year outcomes varied from 28% NSF and 8% mortality in the high-risk NSF/low-risk mortality subset, to 9% NSF and 22% mortality in the low-risk NSF/high-risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture.Considerable variation in 5-year competing mortality risk is present among women in late life with similar 5-year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision-making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years.

  View details for DOI 10.1111/jgs.18859

  View details for PubMedID 38450585

• A protocol for the prospective study of urinary cadmium with risk of fracture, bone loss, and muscle loss. JBMR plus de la Bastide, C., Soares, L., Lui, L. Y., Harrington, J., Cawthon, P., Orwoll, E., Kado, D., Meliker, J. 2024; 8 (2): ziad006

  Abstract

  Cadmium (Cd) is a heavy metal and natural element found in soil and crops with increasing concentrations linked to phosphate fertilizers and sewage sludge applied to crop lands. A large fraction of older US men and woman have documented Cd exposure. Cd exposure has proven health concerns such as risk of lung cancer from inhalation and impaired renal function; however, growing evidence suggests it also influences bone and muscle health. Given that low levels of Cd could affect bone and muscle, we have designed prospective studies using the two largest and most detailed US studies of bone health in older men and women: the Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures. We are investigating the association of urinary cadmium (U-Cd), as a surrogate for long-term Cd exposure, with bone and muscle health. Building off suggestive evidence from mechanistic and cross-sectional studies, this will be the first well-powered prospective study of incident fracture outcomes, bone loss, and muscle loss in relation to U-Cd, an established biomarker of long-term Cd exposure. The following is a proposed protocol for the intended study; if successful, the proposed studies could be influential in directing future US policy to decrease Cd exposure in the US population similar to recent policies adopted by the European Union to limit Cd in fertilizers.

  View details for DOI 10.1093/jbmrpl/ziad006

  View details for PubMedID 38505523

  View details for PubMedCentralID PMC10945722

• Associations between Walking Speed and Gut Microbiome Composition in Older Men from the MrOS Study. The journals of gerontology. Series A, Biological sciences and medical sciences Farsijani, S., Cauley, J. A., Cawthon, P. M., Langsetmo, L., Orwoll, E. S., Kado, D. M., Kiel, D. P., Newman, A. B. 2024

  Abstract

  Gut dysbiosis has been linked to frailty, but its association with early mobility decline is unclear.First, we determined the cross-sectional associations between walking speed and the gut microbiome in 740 older men (84 ± 4y) from the MrOS cohort with available stool samples and 400m walking speed measured in 2014-16. Then, we analyzed the retrospective longitudinal associations between changes in 6m walking speed (from 2005-06 to 2014-16, calculated by simple linear equation) and gut microbiome composition among participants with available data (702/740). We determined gut microbiome composition by 16S sequencing and examined diversity, taxa abundance, and performed network analysis to identify differences in the gut microbiome network of fast vs. slow walkers.Faster 400m walking speed (m/s) was associated with greater microbiome α-diversity (R=0.11; P=0.004). The association between a slower decline in 6m walking speed and higher α-diversity (R=0.07; P=0.054) approached borderline significance. Faster walking speed and less decline in walking speed were associated with higher abundance of genus-level bacteria that produce short-chain fatty acids, and possess anti-inflammatory properties, including Paraprevotella, Fusicatenibacter, and Alistipes, after adjusting for potential covariates (P<0.05). The gut microbiome networks of participants in the first vs. last quartile of walking speed (≤0.9 vs. ≥1.2 m/s) exhibited distinct characteristics, including different centrality measures (P<0.05).Our findings suggest a possible relationship between gut microbiome diversity and mobility function, as indicated by the associations between faster walking speed and less decline in walking speed over ten years with higher gut microbiome diversity in older men.

  View details for DOI 10.1093/gerona/glae030

  View details for PubMedID 38271209

• Night-to-Night Sleep Duration Variability and Gut Microbial Diversity: More Evidence for a Brain-Gut Microbiome-Sleep Connection. Sleep Kado, D. M. 2024

  View details for DOI 10.1093/sleep/zsae005

  View details for PubMedID 38183293

• Optimizing exoskeleton assistance to improve walking speed and energy economy for older adults. Journal of neuroengineering and rehabilitation Lakmazaheri, A., Song, S., Vuong, B. B., Biskner, B., Kado, D. M., Collins, S. H. 2024; 21 (1): 1

  Abstract

  Walking speed and energy economy tend to decline with age. Lower-limb exoskeletons have demonstrated potential to improve either measure, but primarily in studies conducted on healthy younger adults. Promising techniques like optimization of exoskeleton assistance have yet to be tested with older populations, while speed and energy consumption have yet to be simultaneously optimized for any population.We investigated the effectiveness of human-in-the-loop optimization of ankle exoskeletons with older adults. Ten healthy adults > 65 years of age (5 females; mean age: 72 ± 3 yrs) participated in approximately 240 min of training and optimization with tethered ankle exoskeletons on a self-paced treadmill. Multi-objective human-in-the-loop optimization was used to identify assistive ankle plantarflexion torque patterns that simultaneously improved self-selected walking speed and metabolic rate. The effects of optimized exoskeleton assistance were evaluated in separate trials.Optimized exoskeleton assistance improved walking performance for older adults. Both objectives were simultaneously improved; self-selected walking speed increased by 8% (0.10 m/s; p = 0.001) and metabolic rate decreased by 19% (p = 0.007), resulting in a 25% decrease in energetic cost of transport (p = 8e-4) compared to walking with exoskeletons applying zero torque. Compared to younger participants in studies optimizing a single objective, our participants required lower exoskeleton torques, experienced smaller improvements in energy use, and required more time for motor adaptation.Our results confirm that exoskeleton assistance can improve walking performance for older adults and show that multiple objectives can be simultaneously addressed through human-in-the-loop optimization.

  View details for DOI 10.1186/s12984-023-01287-5

  View details for PubMedID 38167151

  View details for PubMedCentralID 6620279

• ASSOCIATIONS BETWEEN WALKING SPEED AND GUT MICROBIOME DIVERSITY IN OLDER MEN FROM THE MROS STUDY Farsijani, S., Cauley, J., Cawthon, P., Langsetmo, L., Orwoll, E., Newman, A., Kado, D. OXFORD UNIV PRESS. 2023: 600

  View details for Web of Science ID 001178258403012

• Breaking Up Sedentary Time Reduces Recurrent Fall Risk, but Not Incident Fracture Risk in Older Men. JBMR plus Roe, L. S., Harrison, S., Cawthon, P. M., Ensrud, K., Gabriel, K. P., Kado, D. M., Cauley, J. A. 2023; 7 (12): e10803

  Abstract

  Apart from physical activity volume, frequent breaks from sedentary bouts and active bouts may differentially reduce fall and fracture risk. We assessed the longitudinal relationship between frequency of breaks from time spent sedentary and frequency of active bouts with recurrent falls and fractures. The sample included 2918 men aged 79.0 ± 5.1 years with free-living activity (SenseWear Armband) at the Osteoporotic Fractures in Men Study (MrOS) year 7 (2007-2009) visit. Men were divided into quartiles by the number of breaks from sedentary bouts (sedentary bout: 5+ minutes sedentary; <1.5 metabolic equivalents of task [METS]) and separately by active bout frequency (active bout: 5+ minutes of activity; ≥1.5 METS). Recurrent falls (2+ falls/year) and fractures were ascertained by self-report; fractures were radiographically confirmed. Generalized estimating equations estimated the recurrent fall odds, with restricted cubic splines applied to assess nonlinear relationships. Cox proportional hazards models estimated fracture risk. Over 4 years of follow-up after year 7, 1025 (35.1%) men were fallers. Over 8.40 ± 4.10 years of follow-up, 640 (21.9%) men experienced a fracture. There was a significant nonlinear U-shaped relationship between number of breaks from sedentary bouts and recurrent falls (p < 0.001); compared with men with few breaks from sedentary bouts (1.4-<13.6), the odds of recurrent falls were lower with a moderate number (13.6-<17.0, odds ratio [OR] = 0.82, 95% confidence interval [CI] 0.66, 1.01; 17.0-<20.4, OR = 0.79, 95% CI 0.64, 0.99), but not with the highest number of breaks from sedentary bouts (20.4-34.6, OR = 1.01, 95% CI 0.81, 1.27). Results remained borderline significant after adjusting for total sedentary time. Men with the highest compared with the lowest number of breaks from sedentary bouts had a lower fracture risk, but the association was attenuated after adjustment for total sedentary time. No associations were observed for active bout frequency. In conclusion, breaking up extended periods of sedentary time reduces fall risk regardless of total sedentary time. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbm4.10803

  View details for PubMedID 38130765

  View details for PubMedCentralID PMC10731095

• Force Plate Leg Power and Velocity Was Associated With the Risk of Major Osteoporotic Fractures (MOF): the Osteoporotic Fractures in Men Study (MrOS) Yu, T., Strotmeyer, E., Heilmann, N., Kado, D., Ensrud, K., Winger, M., Caserotti, P., Cawthon, P., Cauley, J. OXFORD UNIV PRESS. 2023: 177

  View details for Web of Science ID 001266167000531

• The Vitamin D Metabolite Ratio is Associated with Volumetric Bone Density in Older Men. The Journal of clinical endocrinology and metabolism Ginsberg, C., Blackwell, T., Cheng, J. H., Potok, O. A., Cauley, J. A., Ensrud, K., Hsu, S., Kado, D. M., Orwoll, E., Cawthon, P. M., Ix, J. H. 2023

  Abstract

  CONTEXT: Serum 25-hydroxyvitamin D [25(OH)D] is the current marker of vitamin D adequacy, but its relationship with bone health has been inconsistent. The ratio of 24,25-dihydroxyvitamin D3 to 25(OH)D3 (vitamin D metabolite ratio or VMR) is a marker of vitamin D that has been associated with longitudinal changes in BMD and fracture risk.OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) provides information on bone health beyond standard dual-energy x-ray absorptiometry, in that it measures volumetric BMD (vBMD) as well bone strength. The relationship of the VMR with vBMD and bone strength remains unknown.METHODS: We evaluated the associations of the VMR and 25(OH)D3 with vBMD and bone strength, in the distal radius and tibia, assessed by HR-pQCT in 545 men participating in the Osteoporotic Fractures in Men (MrOS) Study. Primary outcomes were vBMD, as well as estimated failure load (EFL, a marker of bone strength), at the distal radius and tibia.RESULTS: The mean age was 84±4 years, 88.3% were White, and 32% had an estimated glomerular filtration rate <60ml/min/1.73m2. In adjusted models, each doubling of VMR was associated with a 9%(3%,16%) higher total vim and a 13%(5%,21%) higher EFL at the distal radius. Results were similar at the distal tibia. 25(OH)D3 concentrations were not associated with any of the studied outcomes.CONCLUSION: Among older men, a higher VMR was associated with vBMD and bone strength while 25(OH)D3 was not. The VMR may serve as a valuable marker of skeletal health in older men.

  View details for DOI 10.1210/clinem/dgad587

  View details for PubMedID 37804103

• A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength. Frontiers in endocrinology Okoro, P. C., Orwoll, E. S., Huttenhower, C., Morgan, X., Kuntz, T. M., McIver, L. J., Dufour, A. B., Bouxsein, M. L., Langsetmo, L., Farsijani, S., Kado, D. M., Pacifici, R., Sahni, S., Kiel, D. P. 2023; 14: 1237727

  Abstract

  The gut microbiome affects the inflammatory environment through effects on T-cells, which influence the production of immune mediators and inflammatory cytokines that stimulate osteoclastogenesis and bone loss in mice. However, there are few large human studies of the gut microbiome and skeletal health. We investigated the association between the human gut microbiome and high resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia in two large cohorts; Framingham Heart Study (FHS [n=1227, age range: 32 - 89]), and the Osteoporosis in Men Study (MrOS [n=836, age range: 78 - 98]). Stool samples from study participants underwent amplification and sequencing of the V4 hypervariable region of the 16S rRNA gene. The resulting 16S rRNA sequencing data were processed separately for each cohort, with the DADA2 pipeline incorporated in the16S bioBakery workflow. Resulting amplicon sequence variants were assigned taxonomies using the SILVA reference database. Controlling for multiple covariates, we tested for associations between microbial taxa abundances and HR-pQCT measures using general linear models as implemented in microbiome multivariable association with linear model (MaAslin2). Abundance of 37 microbial genera in FHS, and 4 genera in MrOS, were associated with various skeletal measures (false discovery rate [FDR] ≤ 0.1) including the association of DTU089 with bone measures, which was independently replicated in the two cohorts. A meta-analysis of the taxa-bone associations further revealed (FDR ≤ 0.25) that greater abundances of the genera; Akkermansia and DTU089, were associated with lower radius total vBMD, and tibia cortical vBMD respectively. Conversely, higher abundances of the genera; Lachnospiraceae NK4A136 group, and Faecalibacterium were associated with greater tibia cortical vBMD. We also investigated functional capabilities of microbial taxa by testing for associations between predicted (based on 16S rRNA amplicon sequence data) metabolic pathways abundance and bone phenotypes in each cohort. While there were no concordant functional associations observed in both cohorts, a meta-analysis revealed 8 pathways including the super-pathway of histidine, purine, and pyrimidine biosynthesis, associated with bone measures of the tibia cortical compartment. In conclusion, our findings suggest that there is a link between the gut microbiome and skeletal metabolism.

  View details for DOI 10.3389/fendo.2023.1237727

  View details for PubMedID 37810879

  View details for PubMedCentralID PMC10551180

• Breaking Up Sedentary Time Reduces Recurrent Fall Risk, but Not Incident Fracture Risk in Older Men JBMR PLUS Roe, L. S., Harrison, S., Cawthon, P. M., Ensrud, K., Gabriel, K., Kado, D. M., Cauley, J. A., Osteoporotic Fractures Men MrOS S 2023

  View details for DOI 10.1002/jbm4.10803

  View details for Web of Science ID 001043111700001

• Advantages and Disadvantages of Random Forest Models for Prediction of Hip Fracture Risk Versus Mortality Risk in the Oldest Old. JBMR plus Langsetmo, L., Schousboe, J. T., Taylor, B. C., Cauley, J. A., Fink, H. A., Cawthon, P. M., Kado, D. M., Ensrud, K. E. 2023; 7 (8): e10757

  Abstract

  Targeted fracture prevention strategies among late-life adults should balance fracture risk versus competing mortality risk. Models have previously been constructed using Fine-Gray subdistribution methods. We used a machine learning method adapted for competing risk survival time to evaluate candidate risk factors and create models for hip fractures and competing mortality among men and women aged 80 years and older using data from three prospective cohorts (Study of Osteoporotic Fractures [SOF], Osteoporotic Fracture in Men study [MrOS], Health Aging and Body Composition study [HABC]). Random forest competing risk models were used to estimate absolute 5-year risk of hip fracture and absolute 5-year risk of competing mortality (excluding post-hip fracture deaths). Models were constructed for both outcomes simultaneously; minimal depth was used to rank and select variables for smaller models. Outcome specific models were constructed; variable importance was used to rank and select variables for inclusion in smaller random forest models. Random forest models were compared to simple Fine-Gray models with six variables selected a priori. Top variables for competing risk random forests were frailty and related components in men while top variables were age, bone mineral density (BMD) (total hip, femoral neck), and frailty components in women. In both men and women, outcome specific rankings strongly favored BMD variables for hip fracture prediction while frailty and components were strongly associated with competing mortality. Model discrimination for random forest models varied from 0.65 for mortality in women to 0.81 for hip fracture in men and depended on model choice and variables included. Random models performed slightly better than simple Fine-Gray model for prediction of competing mortality, but similarly for prediction of hip fractures. Random forests can be used to estimate risk of hip fracture and competing mortality among the oldest old. Modest gains in performance for mortality without hip fracture compared to Fine-Gray models must be weighed against increased complexity. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

  View details for DOI 10.1002/jbm4.10757

  View details for PubMedID 37614297

  View details for PubMedCentralID PMC10443071

• Advantages and Disadvantages of Random Forest Models for Prediction of Hip Fracture Risk Versus Mortality Risk in the Oldest Old JBMR PLUS Langsetmo, L. T., Schousboe, J. C., Taylor, B. A., Cauley, J. A., Fink, H. M., Cawthon, P. M., Kado, D. E., Ensrud, K., Osteoporotic Fractures Men 2023

  View details for DOI 10.1002/jbm4.10757

  View details for Web of Science ID 001022730600001

• The Association of Intensive Blood Pressure Treatment and Non-Fatal Cardiovascular or Serious Adverse Events in Older Adults with Mortality: Mediation Analysis in SPRINT. European journal of preventive cardiology Krishnaswami, A., Rich, M. W., Kwak, M. J., Goyal, P., Forman, D. E., Damluji, A. A., Solomon, M., Rana, J. S., Kado, D. M., Odden, M. C. 2023

  Abstract

  Randomized clinical trials of hypertension treatment intensity evaluate effects on incident major adverse cardiovascular events (MACE) and serious adverse events (SAE). Occurrences after a non-fatal index event have not been rigorously evaluated. The current aim was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure treatment to mortality mediated through a non-fatal MACE or non-fatal SAE in 9,361 Systolic Blood Pressure Intervention trial participants.Logistic regression and causal mediation modeling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM).The direct effect of intensive treatment was a lowering of ACM [OR 0.75, 0.60-0.94]. The MACE-mediated effect substantially attenuated [OR 0.96, 0.92-0.99] ACM; while the SAE-mediated effect was associated with increased [OR 1.03, 1.01-1.05] ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted the SAE incidence was 3.9-fold higher than MACE incidence (13.7% vs 3.5%), and there was a total of 365 (3.9%) ACM with non-CVM 2.6-fold higher than CVM [2.81% (263/9,361) vs 1.09% (102/9,361)]. The SAE to MACE and non-CVM to CVM preponderance was across all age-groups with the ≥ 80-year age group having the highest differences.The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when MACE-mediated and possibly harmful when SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.

  View details for DOI 10.1093/eurjpc/zwad132

  View details for PubMedID 37185634

• Associations of Lean Mass, Muscular Strength, and Physical Function with Trabecular Bone Score in Older Adults. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry Seaton, M. P., Nichols, J. F., Rauh, M. J., Kado, D. M., Wetherell, J. L., Lenze, E. J., Wing, D. 2023: 101370

  Abstract

  INTRODUCTION/BACKGROUND: Trabecular bone score (TBS) is an indirect measurement of bone quality and microarchitecture determined from dual-energy X-ray absorptiometry (DXA) imaging of the lumbar spine. TBS predicts fracture risk independent of bone mass/density, suggesting this assessment of bone quality adds value to the understanding of patients' bone health. While lean mass and muscular strength have been associated with higher bone density and lower fracture risk among older adults, the literature is limited regarding the relationship of lean mass and strength with TBS. The purpose of this study was to determine associations of DXA-determined total body and trunk lean mass, maximal muscular strength, and gait speed as a measure of physical function, with TBS in 141 older adults (65-84 yr, 72.5 +/- 5.1 yr, 74% women).METHODOLOGY: Assessments included lumbar spine (L1-L4) bone density and total body and trunk lean mass by DXA, lower body (leg press) and upper body (seated row) strength by one repetition maximum tests, hand grip strength, and usual gait speed. TBS was derived from the lumbar spine DXA scan. Multivariable linear regression determined the contribution of proposed predictors to TBS.RESULTS: After adjusting for age, sex, and lumbar spine bone density, upper body strength significantly predicted TBS (unadjusted/adjusted R2= 0.16/ 0.11, beta coefficient =0.378, p=0.005), while total body lean mass index showed a trend in the expected direction (beta coefficient =0.243, p=0.053). Gait speed and grip strength were not associated with TBS (p>0.05).CONCLUSION: Maximum strength of primarily back muscles measured as the seated row appears important to bone quality as measured by TBS, independent of bone density. Additional research on exercise training targeting back strength is needed to determine its clinical utility in preventing vertebral fractures among older adults.

  View details for DOI 10.1016/j.jocd.2023.101370

  View details for PubMedID 37100686

• CAN MUSCLE MASS EXPLAIN THE RELATIONSHIP BETWEEN EGFRDIFF (=EGFRCYSEGFRCR) AND FRAILTY IN OLDER MEN? Yuan, J. H., Rifkin, D. E., Ginsberg, C., Cawthon, P., Kado, D. M., Bauer, S. R., Ensrud, K., Hoffman, A., Potok, O. W B SAUNDERS CO-ELSEVIER INC. 2023: S127

  View details for Web of Science ID 000951098100437

• Vitamin D Metabolite Ratio and Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis. Circulation. Cardiovascular imaging Ginsberg, C., Hoofnagle, A. N., Katz, R., Cheng, J. H., Hsu, S., Budoff, M. J., Kado, D. M., Kestenbaum, B., Siscovick, D. S., Michos, E. D., Ix, J. H., de Boer, I. H. 2023; 16 (3): e015055

  View details for DOI 10.1161/CIRCIMAGING.122.015055

  View details for PubMedID 36943910

• FSH, BMAT Composition, and Longitudinal Changes in BMAT in Older Adults Kim, T., Hue, T., Ewing, S., Li, X., Sigurosson, S., Guonason, V., Velduis-Vlug, A., Kado, D., Vittinghoff, E., Wu, K., Koh, E., Rosen, C., Zaidi, M., Schwartz, A., Schafer, A. WILEY. 2023: 219

  View details for Web of Science ID 001008985201189

• Performance of FRAX and Garvan Fracture Risk Assessment Tools in Hip Fracture Prediction in US Adults Aged 80 Year and Older: Findings from the Study of Osteoporotic Fractures (SOF) and Osteoporotic Fractures in Men (MrOS) Study Ensrud, K., Schousboe, J., Fink, H., Leslie, W., Taylor, B., Cawthon, P., Kado, D., Lane, N., Crandall, C., Cauley, J., Langsetmo, L. WILEY. 2023: 40

  View details for Web of Science ID 001008985200115

• Balancing Fracture Risk versus Risk of Mortality Before Fracture Among Women Age 80 Years or Older Schousboe, J., Langsetmo, L., Fink, H., Kado, D., Cauley, J., Taylor, B., Ensrud, K. WILEY. 2023: 79

  View details for Web of Science ID 001008985200238

• Machine Learning Approach to Prediction of 5-year Fracture Risk vs. 5-year Mortality Risk in Men in Late Life Langsetmo, L., Schousboe, J. T., Taylor, B. C., Cauley, J. A., Fink, H. A., Cawthon, P. M., Stefanick, M. L., Kado, D. M., Ensrud, K. E. WILEY. 2023: 77-78

  View details for Web of Science ID 001008985200233

• The Association of Metabolic Syndrome and Obesity With Clinical Hip Osteoarthritis in the Study of Osteoporotic Fractures and the Osteoporotic Fractures in Men Study Cohorts. ACR open rheumatology Cheng, K. Y., Strotmeyer, E. S., Kado, D. M., Schousboe, J. T., Schenk, S., Nevitt, M., Lane, N. E., Hughes-Austin, J. M. 2023

  Abstract

  Metabolic dysregulation frequently co-occurs with obesity, which has been shown to be a risk factor for lower extremity osteoarthritis (OA). We evaluated the association between metabolic syndrome (MetS), alone and in combination with obesity, and hip OA.In two parallel cross-sectional analyses, we studied 403 women from the Study of Osteoporotic Fractures (SOF) and 2354 men from the Osteoporotic Fractures in Men (MrOS) study. We used multivariable logistic regression to evaluate associations of obesity (body mass index ≥30 kg/m2 ) and/or MetS (three of five National Cholesterol Education Program Adult Treatment Panel III criteria) with clinical hip OA, defined as a modified Croft score of 2 or more or total hip replacement, and pain or limited range of motion. Our analysis adjusted for demographics.Approximately 3.5% of SOF women and 5.4% of MrOS men had clinical hip OA. Among women, obesity was not associated with hip OA, yet those with MetS had a 365% higher odds of hip OA (95% CI: 1.37-15.83). Among men, those who had obesity had a 115% higher odds of hip OA (95% CI: 1.39-3.32), yet MetS was not associated with hip OA. There was no interaction between MetS, obesity, and hip OA in either women or men.In women, but not in men, MetS was associated with hip OA. In men, but not in women, obesity was associated with hip OA. These findings suggest that mechanical effects of obesity may predominate in the pathogenesis of hip OA in men, whereas metabolic effects predominate in women.

  View details for DOI 10.1002/acr2.11518

  View details for PubMedID 36694301

• Association of subjective and objective measures of sleep with gut microbiota composition and diversity in older men: The Osteoporotic Fractures in Men (MrOS) study. The journals of gerontology. Series A, Biological sciences and medical sciences Estaki, M., Langsetmo, L., Shardell, M., Mischel, A., Jiang, L., Zhong, Y., Kaufmann, C., Knight, R., Stone, K., Kado, D. 2023

  Abstract

  BACKGROUND: Growing evidence suggests bi-directional links between gut microbiota and sleep quality as shared contributors to health. Little is known about the relationship between microbiota and sleep among older persons.METHODS: We used 16S rRNA sequencing to characterize stool microbiota among men (n=606, mean [SD] age = 83.9 [3.8]) enrolled in the Osteoporotic Fractures in Men (MrOS) study from 2014-16. Sleep was assessed concurrently by questionnaire (Pittsburgh Sleep Quality index [PSQI]), and activity monitor to examine timing (acrophase) and regularity of patterns (F-statistic). Alpha diversity was measured using Faith's phylogenetic diversity (PD). Beta diversity was calculated with robust Aitchison distances (RPCA) and phylogenetic-RPCA (PRPCA). Their association with sleep variables was tested with a partial distance-based redundancy analysis (dbRDA). Predictive-ratio biomarkers associated with sleep measurements were identified with CoDACoRe.RESULTS: In unadjusted analyses, men with poor sleep (PSQI >5) tended to have lower alpha-diversity compared to men with normal sleep (Faith's PD, beta= -0.15; 95% CI:-0.30-0.01, p=0.06). Sleep regularity was significantly associated with RPCA and PRPCA, even after adjusting for site, batch, age, ethnicity, body mass index, diabetes, antidepressant and sleep medication use, and health behaviors (RPCA/PRPCA dbRDA p=.033/0.002). In taxonomic analysis, a ratio of 7:6 bacteria for better regularity (p = 0.0004) and 4:7 for worse self-reported sleep (p = 0.005) were differentially abundant: some butyrate-producing bacteria were associated with better sleep characteristics.CONCLUSIONS: Subjective and objective indicators of sleep quality suggest that older men with better sleep patterns are more likely to harbor butyrate-producing bacteria associated with better health.

  View details for DOI 10.1093/gerona/glad011

  View details for PubMedID 36655399

• The Vitamin D Metabolite Ratio and Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis Ginsberg, C., Hoofnagle, A. N., Katz, R., Cheng, J., Hsu, S., Budoff, M. J., Kado, D. M., Kestenbaum, B. R., Michos, E. D., Siscovick, D., Ix, J. H., de Boer, I. H. AMER SOC NEPHROLOGY. 2022: 653

  View details for Web of Science ID 001261054404219

• THE ASSOCIATION BETWEEN OBJECTIVE MEASURES OF INTERMITTENT SEDENTARY BREAKS WITH RECURRENT FALL RISK IN OLDER MEN Roe, L., Harrison, S., Cawthon, P., Ensrud, K., Gabriel, K., Kado, D., Cauley, J. OXFORD UNIV PRESS. 2022: 106-107

  View details for Web of Science ID 000913044000414

• Hyperkyphosis and mortality risk in older men: The osteoporotic fractures in men study. Journal of the American Geriatrics Society Cours, A., Huang, M., Fink, H., Ensrud, K. E., Schousboe, J. T., Katzman, W., Schneider, D., Lane, N. E., Cawthon, P., Kado, D. M. 2022

  Abstract

  INTRODUCTION: Hyperkyphosis commonly affects older people but is not widely acknowledged as a clinically actionable problem, especially in men. There are several techniques to quantify kyphosis including the blocks and Cobb angle measurements. This study includes both kyphosis measures to investigate whether older men with accentuated kyphosis may be at increased mortality risk.METHODS: Men aged ≥65years (N=5994) were recruited to participate in the MrOS prospective cohort study from 2000 to 2002 (baseline). Our primary cohort included 2931 enrollees (mean age 79.3years; SD 5.2) who underwent blocks-measured kyphosis from 2006 to 2009. Our secondary cohort included 2351 participants who underwent radiographic Cobb angle measurements at baseline. Cox proportional hazards analyses were used to determine association between kyphosis and all-cause mortality while adjusting for prevalent radiographic vertebral fractures, bone mineral density, incident fractures, gait speed, timed chair stands, self-reported health, alcohol use, medical co-morbidities, and physical activity.RESULTS: During a mean follow-up of 8.3 (SD 3.2) years, 1393 participants died in the primary cohort. In this group, compared to men with 0-1 block kyphosis, increasing blocks-measured kyphosis was associated with increased mortality (HR: 1.26-1.53, p trend <0.001). With addition of prevalent vertebral fracture to adjusted models, the association remained significant in participants with severe kyphosis (3+ blocks-measured). Similarly, with addition of chair stand performance the association remained significant for 4+ blocks kyphosis. Walking speed did not attenuate the association of kyphosis and mortality. In the secondary cohort, there were no significant associations between radiographic Cobb angle kyphosis and mortality.CONCLUSIONS: Increasing blocks-measured kyphosis was associated with a greater risk of mortality in older men, indicating that hyperkyphosis identified on physical exam should be considered a clinically significant finding that may warrant further evaluation and treatment.

  View details for DOI 10.1111/jgs.18100

  View details for PubMedID 36307923

• Associations of 24-hour Light Exposure and Activity Patterns and Risk of Cognitive Impairment and Decline in Older Men: The MrOS Sleep Study. The journals of gerontology. Series A, Biological sciences and medical sciences Blackwell, T. L., Figueiro, M. G., Tranah, G. J., Zeitzer, J. M., Yaffe, K., Ancoli-Israel, S., Kado, D. M., Ensrud, K. E., Lane, N. E., Leng, Y., Stone, K. L., Osteoporotic Fractures in Men (MrOS) Study Group 2022

  Abstract

  BACKGROUND: Older men with worse alignment of activity and light may have lower levels of cognition and increased rates of cognitive decline.METHODS: This cohort consisted of 1,036 older men (81.1 ± 4.6 years) from the MrOS Sleep Study (2009-2012). Light and activity levels were gathered by wrist actigraphy. Phasor analysis was used to quantify alignment of light-dark and rest-activity patterns (magnitude) and their temporal relationship (angle). Global cognitive function (Modified Mini-Mental State examination, 3MS) and executive function (Trails B test) were measured, then repeated 4.2 ± 0.8 years later. Linear regression models examined the associations of phasor magnitude and angle with cognition and cognitive decline. Models were adjusted for age, clinic, race, education and season.RESULTS: Smaller phasor magnitude (worse aligned light and activity patterns) was associated with lower initial level and increased decline in executive function. Compared to those with higher phasor magnitude, those with lower magnitude took an average of 11.1 seconds longer to complete the Trails B test (Quartile 1 vs. Quartile 4, p=.02). After follow-up, Trails B completion time increased an average of 5.5 seconds per standard deviation increase in phasor magnitude (95% CI 0.7-10.4, p=.03). There were no associations with phasor angle, and none with magnitude and global cognition (3MS).CONCLUSIONS: Among older men, worse alignment of light and activity patterns was associated with worse initial performance and increased decline in executive function, but not related to global cognition. Interventions that improve alignment of light and activity may slow cognitive decline in older adults.

  View details for DOI 10.1093/gerona/glac187

  View details for PubMedID 36156079

• Associations Of Lean Mass And Muscular Strength With Trabecular Bone Score In Older Adults Seaton, M., Wing, D., Shen, J., Rauh, M. J., Kado, D., Godino, J. G., Nichols, J. F. LIPPINCOTT WILLIAMS & WILKINS. 2022: 37

  View details for Web of Science ID 000888056600106

• Characteristics Associated with 5-year Fracture Risk vs. 5-year Mortality Risk Among Late-life Men. The journals of gerontology. Series A, Biological sciences and medical sciences Langsetmo, L., Schousboe, J. T., Taylor, B. C., Cauley, J. A., Fink, H. A., Cawthon, P. M., Stefanick, M. L., Kado, D. M., Kats, A. M., Ensrud, K. E., Osteoporotic Fractures in Men (MrOS) Research Group 2022

  Abstract

  BACKGROUND: Identifying late-life men who might benefit from treatment to prevent fracture is challenging given high mortality. Our objective was to evaluate risks of clinical fracture, hip fracture, and mortality prior to fracture among men ≥80 years.METHODS: Study participants included 3,145 community-dwelling men (mean [SD] age 83 [2.8] years) from the Osteoporotic Fractures in Men (MrOS) Study. We used separate multivariable Fine-Gray competing risk models with pre-specified risk factors [age, hip bone mineral density (BMD), recent fracture (<5 years), fall history (previous year), and multimorbidity (# conditions)] to estimate sub-distribution hazard ratios and absolute 5-year risks of any clinical fracture and mortality prior to clinical fracture. Secondary analysis considered hip fracture.RESULTS: There were 414 incident clinical fractures and 595 deaths without prior fracture within 5 years. BMD, fall history, and recent fracture were strong predictors of clinical fracture. Age and multimorbidity were strong predictors of mortality before fracture. After accounting for competing risks, age, BMD, and fall history were each associated with both risk of hip fracture and mortality before hip fracture. Model discrimination varied from 0.65 (mortality before fracture) to 0.79 (hip fracture). Estimated mortality differed substantially among men with similar clinical fracture risk due to modest correlation between fracture risk and competing mortality risk=0.37.CONCLUSIONS: In late-life men, strong risk factors for clinical fracture and hip fracture include fall history, BMD, and recent fracture. Osteoporosis drug treatment decisions may be further enhanced by consideration of fracture risk versus overall life expectancy.

  View details for DOI 10.1093/gerona/glac159

  View details for PubMedID 35917212

• Lower Leg Power and Grip Strength are Associated with Increased Fall Injury Risk in Older Men: the Osteoporotic Fractures in Men (MrOS) Study. The journals of gerontology. Series A, Biological sciences and medical sciences Winger, M. E., Caserotti, P., Cauley, J. A., Boudreau, R. M., Piva, S. R., Cawthon, P. M., Orwoll, E. S., Ensrud, K. E., Kado, D. M., Strotmeyer, E. S., Osteoporotic Fractures in Men (MrOS) Research Group 2022

  Abstract

  BACKGROUND: Past research has not investigated both lower-extremity power and upper-extremity strength in the same fall injury study, particularly non-fracture fall injuries.METHODS: In the Osteoporotic Fractures in Men (MrOS) Study (baseline: N=5,994; age 73.7±5.9 years; 10.2% non-White), fall injuries (yes/no) were assessed prospectively with questionnaires approximately every 3 years over 9 years. Maximum leg power (Watts) from Nottingham single leg press and maximum grip strength (kg) from handheld dynamometry were assessed at baseline and standardized to kg body weight. Physical performance included gait speed (6m usual; narrow walk) and chair stands speed.RESULTS: Of men with ≥1/4 follow-ups (N=5,178; age 73.4±5.7 years), 40.4% (N=2,090) had ≥1 fall injury. In fully adjusted repeated-measures logistic regressions, lower power/kg and grip strength/kg had higher fall injury risk (trend across quartiles: both p<0.0001), with lower quartiles at significantly increased risk vs. highest Q4 except for grip strength Q3 vs. Q4. Fall injury risk was 19% higher per 1 standard deviation (SD) lower power/kg (95%CI: 1.12-1.26) and 16% higher per SD lower grip strength/kg (95%CI: 1.10-1.23). In models including both leg power/kg and grip strength/kg, ORs were similar and independent of each other and physical performance (leg power/kg OR per SD=1.13, 95%CI: 1.06-1.20; grip strength/kg OR per SD=1.11, 95%CI: 1.05-1.17).CONCLUSIONS: Lower leg power/kg and grip strength/kg predicted future fall injury risk in older men independent of physical performance. Leg power potentially identifies fall injury risk better than grip strength at higher muscle function, though grip strength may be more suitable in clinical/practice settings.

  View details for DOI 10.1093/gerona/glac122

  View details for PubMedID 35662329

• Slower upper extremity function in older adults with hyperkyphosis negatively impacts the 6-min walk test. BMC musculoskeletal disorders Fukuoka, Y., Katzman, W. B., Gladin, A., Lane, N. E., Kado, D. M., Oh, Y. J. 2022; 23 (1): 505

  Abstract

  BACKGROUND: Approximately 30% to 40% of older adults have hyperkyphosis, defined as excessive curvature of the thoracic spine. Hyperkyphosis is associated with increased morbidity and mortality. This study aimed to determine whether hyperkyphosis (Cobb's angle) and upper extremity tasks were independently associated with the 6-min walk test (6MWT) in community-dwelling older adults with hyperkyphosis.METHODS: In this cross-sectional study, we studied 71 women and 28 men aged 60-87 from the study of hyperkyphosis, exercise, and function trial (SHEAF) who had kyphosis, 3 timed upper extremity tasks and the 6MWT assessed at their baseline visit. We used standing lateral spine radiographs and a standardized protocol for thoracic kyphosis (T4-T12) to measure Cobb angle of kyphosis. In addition, 3 activity of daily living (ADL) extremity tests (putting on and removing a laboratory coat, picking up a penny from the floor, and lifting a 7-lb. book to a shelf) were used.RESULTS: The mean±SD age was 70.1±6.1years. The mean±SD Cobb angle of kyphosis was 57.4±12.5 degrees. On average±SD, the participants walked 504.8±84.2m in 6min and took 2.4±2.2 prescription medications. The mean±SD height was 164.7±8.5cm, weight was 68.7±13.1kg, and BMI was 25.2±4.0kg/m2. Multivariate regression revealed that age, height, upper extremity book lift task, and the number of prescribed medications were significant predictors of performance on the 6MWT (p<0.05).CONCLUSIONS: While kyphosis was not associated with the 6MWT, timed tests of upper extremity function indicated that upper body dynamics can affect walking performance. In addition, sociodemographic factors and the number of prescribed medications were significant contributing factors to the 6MWT in older adults with mild to moderate hyperkyphosis. These results illustrate multifactorial influences on physical performance and the need for an integrated and targeted approach in helping older hyperkyphotic adults maintain healthy physical functioning as they age.

  View details for DOI 10.1186/s12891-022-05455-x

  View details for PubMedID 35624469

• Repeat Bone Mineral Density Screening Measurement and Fracture Prediction in Older Men: A Prospective Cohort Study. The Journal of clinical endocrinology and metabolism Ensrud, K. E., Lui, L., Crandall, C. J., Orwoll, E. S., Langsetmo, L., Schousboe, J. T., Fink, H. A., Lane, N. E., Kado, D. M., Cauley, J. A., Stefanick, M. L., Cawthon, P. M. 2022

  Abstract

  CONTEXT: Whether repeated bone mineral density (BMD) screening improves fracture prediction in men is uncertain.OBJECTIVE: Evaluate whether a second BMD 7 years after the initial BMD improves fracture prediction in older men.METHODS: 3,651 community-dwelling men (mean age 79.1 years) with total hip BMD at baseline and Year 7 (Y7). Self-reported fractures after Y7 confirmed by radiographic reports. Fracture prediction assessed using Cox proportional hazards regression and logistic regression with receiver operating characteristic curves for models based on initial BMD, BMD change, and the combination of initial BMD and BMD change (combination model).RESULTS: During an average follow-up of 8.2 years after Y7, 793 men experienced ≥1 clinical fractures including 426 men with major osteoporotic fractures (MOF) and 193 men with hip fractures. Both initial BMD and BMD change were associated with risk of fracture outcomes independent of each other, but the association was stronger for initial BMD. For example, the multivariable hazard ratio of MOF in the combination model per 1 SD decrement in BMD was 1.76 (95% CI 1.57-1.98) for initial BMD and 1.19 (95% CI 1.08-1.32) for BMD change. Discrimination of fracture outcomes with initial BMD models was somewhat better than with BMD change models and similar to combination models (AUC value for MOF 0.68 [95% CI 0.66-0.71] for initial BMD model, 0.63 [95% CI 0.61-0.66] for BMD change model, and 0.69 [95% CI 0.66-0.71] for combination model).CONCLUSION: Repeating BMD after 7 years did not meaningfully improve fracture prediction at the population level in community-dwelling older men.

  View details for DOI 10.1210/clinem/dgac324

  View details for PubMedID 35587517

• Deep Learning Classification of Spinal Osteoporotic Compression Fractures on Radiographs using an Adaptation of the Genant Semiquantitative Criteria. Academic radiology Dong, Q., Luo, G., Lane, N. E., Lui, L., Marshall, L. M., Kado, D. M., Cawthon, P., Perry, J., Johnston, S. K., Haynor, D., Jarvik, J. G., Cross, N. M. 2022

  Abstract

  RATIONALE AND OBJECTIVES: Osteoporosis affects 9% of individuals over 50 in the United States and 200 million women globally. Spinal osteoporotic compression fractures (OCFs), an osteoporosis biomarker, are often incidental and under-reported. Accurate automated opportunistic OCF screening can increase the diagnosis rate and ensure adequate treatment. We aimed to develop a deep learning classifier for OCFs, a critical component of our future automated opportunistic screening tool.MATERIALS AND METHODS: The dataset from the Osteoporotic Fractures in Men Study comprised 4461 subjects and 15,524 spine radiographs. This dataset was split by subject: 76.5% training, 8.5% validation, and 15% testing. From the radiographs, 100,409 vertebral bodies were extracted, each assigned one of two labels adapted from the Genant semiquantitative system: moderate to severe fracture vs. normal/trace/mild fracture. GoogLeNet, a deep learning model, was trained to classify the vertebral bodies. The classification threshold on the predicted probability of OCF outputted by GoogLeNet was set to prioritize the positive predictive value (PPV) while balancing it with the sensitivity. Vertebral bodies with the top 0.75% predicted probabilities were classified as moderate to severe fracture.RESULTS: Our model yielded a sensitivity of 59.8%, a PPV of 91.2%, and an F1 score of 0.72. The areas under the receiver operating characteristic curve (AUC-ROC) and the precision-recall curve were 0.99 and 0.82, respectively.CONCLUSION: Our model classified vertebral bodies with an AUC-ROC of 0.99, providing a critical component for our future automated opportunistic screening tool. This could lead to earlier detection and treatment of OCFs.

  View details for DOI 10.1016/j.acra.2022.02.020

  View details for PubMedID 35351363

• Strong discordance in factors associated with 5-year risk of fracture vs. 5-year risk of mortality among men aged 80 and older: findings from the Osteoporotic Fractures in Men [MrOS] study Langsetmo, L., Schousboe, J. T., Taylor, B. C., Cauley, J. A., Fink, H. A., Cawthon, P. M., Stefanick, M. L., Kado, D. M., Kats, A. M., Ensrud, K. E. WILEY. 2022: 343-344

  View details for Web of Science ID 000778074501469

• Assessment of Semiquantitative Spinal Deformity Index May Improve Fracture Prediction Among Older Men with Prevalent Vertebral Fracture Schousboe, J., Langsetmo, L., Kats, A., Kado, D., Lane, N., Taylor, B., Ensrud, K. WILEY. 2022: 139

  View details for Web of Science ID 000778074500416

• Repeat Bone Mineral Density Measurement and Fracture Prediction in Older Men: Findings from the Osteoporotic Fractures in Men (MrOS) Study Ensrud, K., Lui, L., Crandall, C., Orwoll, E., Langsetmo, L., Schousboe, J., Fink, H., Lane, N., Kado, D., Cauley, J., Cawthon, P. WILEY. 2022: 184

  View details for Web of Science ID 000778074500552

• Saturated and Unsaturated Bone Marrow Lipids Have Distinct Effects on Bone Density and Fracture Risk in Older Adults. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Woods, G. N., Ewing, S. K., Schafer, A. L., Gudnason, V., Sigurdsson, S., Lang, T., Hue, T. F., Kado, D. M., Vittinghoff, E., Rosen, C., Li, X., Schwartz, A. V. 1800

  Abstract

  Greater bone marrow adiposity (BMAT) is associated with lower bone mineral density (BMD) and vertebral fractures; less is known about BMAT composition and bone. We studied BMAT composition and bone outcomes in 465 participants from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. BMAT saturation and unsaturation, measured with magnetic resonance spectroscopy, were defined as the ratio of saturated (1.3 ppm peak) or unsaturated (5.3 ppm peak) lipid to total marrow contents, respectively. At baseline and follow-up visits, spine and hip BMD were assessed with quantitative computed tomography (QCT) and dual x-ray absorptiometry (DXA) and vertebral fractures were identified with DXA. Incident clinical fractures were identified through medical records for up to 8.8years of follow-up. Associations between BMAT composition and BMD, bone loss, and fractures were evaluated in adjusted regression models. At baseline, mean participant age was 81.7 (SD 4.3) years, mean BMAT unsaturation was 3.5% (SD 1.0) and mean saturation was 46.3% (SD 7.2) in the full cohort (47.7% women). Each SD increase in BMAT saturation was associated with lower trabecular BMD: -23.6% (spine), -13.0% (total hip) (all p<0.0001). Conversely, BMAT unsaturation (per SD increase) was associated with higher trabecular BMD: +17.5% (spine), +11.5% (total hip), (all p<0.001). BMAT saturation (per SD increase) was associated with greater risk for prevalent [OR=1.46 (1.11-1.92)] and incident [OR=1.55 (1.03-2.34)] vertebral fracture. BMAT unsaturation (per SD increase) was associated with lower risk for incident vertebral fracture [OR=0.58 (0.38-0.89)]. In gender stratified analyses, BMAT saturation and unsaturation had opposite associations with incident clinical fracture among men. In general, saturated marrow lipids were associated with worse skeletal outcomes while unsaturated lipids with better outcomes. We recommend that future studies of marrow fat and skeletal health report measurements of saturated and unsaturated marrow lipids, rather than total marrow fat content alone. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbmr.4504

  View details for PubMedID 35038186

• Follicle-stimulating hormone level and changes in bone mass and body composition in older women and men. The Journal of clinical endocrinology and metabolism Wu, K. C., Ewing, S. K., Li, X., Sigurdsson, S., Gudnason, V., Kado, D. M., Hue, T. F., Woods, G. N., Veldhuis-Vlug, A. G., Vittinghoff, E., Zaidi, M., Rosen, C. J., Lang, T., Kim, T. Y., Schwartz, A. V., Schafer, A. L. 2021

  Abstract

  CONTEXT: Follicle-stimulating hormone (FSH) may have independent actions on bone remodeling and body fat regulation. Cross-sectionally, we have shown that serum FSH is associated with bone mineral density (BMD) and body fat in older postmenopausal women, but it remains unknown whether FSH predicts bone and fat changes.OBJECTIVE: We examined whether baseline FSH level is associated with subsequent bone loss or body composition changes in older adults.SETTING, DESIGN, PARTICIPANTS: We studied 162 women and 158 men (mean age 82 ±4 years) from the AGES-BMA cohort, a substudy of the AGES-Reykjavik Study of community-dwelling older adults. Skeletal health and body composition were characterized at baseline and 3 years later.MAIN OUTCOMES: Annualized change in BMD and body composition by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Models were adjusted for serum estradiol and testosterone levels.RESULTS: There was no evidence for an association between baseline FSH level and change in BMD or body composition by DXA or QCT. For femoral neck areal BMD, adjusted mean difference (95% CI) per SD increase in FSH was 1.3 (-0.7, 3.3) mg/cm 2/year in women, and -0.2 (-2.6, 2.2) mg/cm 2/year in men. For visceral fat, adjusted mean difference (95% CI) per SD increase in FSH was 1.80 (-0.03, 3.62) cm 2/year in women, and -0.33 (-3.73, 3.06) cm 2/year in men.CONCLUSIONS: Although cross-sectional studies and studies in perimenopausal women have demonstrated associations between FSH and BMD and body composition, in older adults, FSH level is not associated with bone mass or body composition changes.

  View details for DOI 10.1210/clinem/dgab481

  View details for PubMedID 34212197

• Hepatic Steatosis is Negatively Associated with Bone Mineral Density in Children JOURNAL OF PEDIATRICS Chun, L. F., Yu, E. L., Sawh, M., Bross, C., Nichols, J., Polgreen, L., Knott, C., Schlein, A., Sirlin, C. B., Middleton, M. S., Kado, D. M., Schwimmer, J. B. 2021; 233: 105-+

  Abstract

  To evaluate the relationship between hepatic steatosis and bone mineral density (BMD) in children. In addition, to assess 25-hydroxyvitamin D levels in the relationship between hepatic steatosis and BMD.A community-based sample of 235 children was assessed for hepatic steatosis, BMD, and serum 25-hydroxyvitamin D. Hepatic steatosis was measured by liver magnetic resonance imaging proton density fat fraction (MRI-PDFF). BMD was measured by whole-body dual-energy x-ray absorptiometry.The mean age of the study population was 12.5 years (SD 2.5 years). Liver MRI-PDFF ranged from 1.1% to 40.1% with a mean of 9.3% (SD 8.5%). Across this broad spectrum of hepatic fat content, there was a significant negative relationship between liver MRI-PDFF and BMD z score (R = -0.421, P < .001). Across the states of sufficiency, insufficiency, and deficiency, there was a significant negative association between 25-hydroxyvitamin D and liver MRI-PDFF (P < .05); however, there was no significant association between vitamin D status and BMD z score (P = .94). Finally, children with clinically low BMD z scores were found to have higher alanine aminotransferase (P < .05) and gamma-glutamyl transferase (P < .05) levels compared with children with normal BMD z scores.Across the full range of liver MRI-PDFF, there was a strong negative relationship between hepatic steatosis and BMD z score. Given the prevalence of nonalcoholic fatty liver disease and the critical importance of childhood bone mineralization in protecting against osteoporosis, clinicians should prioritize supporting bone development in children with nonalcoholic fatty liver disease.

  View details for DOI 10.1016/j.jpeds.2021.01.064

  View details for Web of Science ID 000655264900020

  View details for PubMedID 33545191

  View details for PubMedCentralID PMC8154638

• Quantifying the Effects of Aging on Morphological and Cellular Properties of Human Female Pelvic Floor Muscles ANNALS OF BIOMEDICAL ENGINEERING Rieger, M., Duran, P., Cook, M., Schenk, S., Shah, M., Jacobs, M., Christman, K., Kado, D. M., Alperin, M. 2021

  Abstract

  Age-related pelvic floor muscle (PFM) dysfunction is a critical defect in the progression to pelvic floor disorders (PFDs). Despite dramatic prevalence of PFDs in older women, the underlying pathophysiology of age-related PFM dysfunction remains poorly understood. Using cadaveric specimens, we quantified aging effects on functionally relevant PFM properties and compared PFMs with the appendicular muscles from the same donors. PFMs, obturator internus, and vastus lateralis were procured from younger (N = 4) and older (N = 11) donors with known obstetrical and medical history. Our findings demonstrate that PFMs undergo degenerative, rather than atrophic, alterations. Importantly, age-related fibrotic degeneration disproportionally impacts PFMs compared to the appendicular muscles. We identified intramuscular lipid accumulation as another contributing factor to the pathological alterations of PFMs with aging. We observed a fourfold decrease in muscle stem cell (MuSC) pool of aged relative to younger PFMs, but the MuSC pool of appendicular muscles from the same older donors was only twofold lower than in younger group, although these differences were not statistically significant. Age-related degeneration appears to disproportionally impact PFMs relative to the appendicular muscles from the same donors. Knowledge of tissue- and cell-level changes in aged PFMs is essential to promote our understanding of the mechanisms governing PFM dysfunction in older women.

  View details for DOI 10.1007/s10439-021-02748-5

  View details for Web of Science ID 000626407700003

  View details for PubMedID 33683527

• Gut microbiome pattern reflects healthy ageing and predicts survival in humans NATURE METABOLISM Wilmanski, T., Diener, C., Rappaport, N., Patwardhan, S., Wiedrick, J., Lapidus, J., Earls, J. C., Zimmer, A., Glusman, G., Robinson, M., Yurkovich, J. T., Kado, D. M., Cauley, J. A., Zmuda, J., Lane, N. E., Magis, A. T., Lovejoy, J. C., Hood, L., Gibbons, S. M., Orwoll, E. S., Price, N. D. 2021; 3 (2): 274-+

  Abstract

  The gut microbiome has important effects on human health, yet its importance in human ageing remains unclear. In the present study, we demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique to individuals with age. We leverage three independent cohorts comprising over 9,000 individuals and find that compositional uniqueness is strongly associated with microbially produced amino acid derivatives circulating in the bloodstream. In older age (over ~80 years), healthy individuals show continued microbial drift towards a unique compositional state, whereas this drift is absent in less healthy individuals. The identified microbiome pattern of healthy ageing is characterized by a depletion of core genera found across most humans, primarily Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a 4-year follow-up. Our analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy ageing, which is characterized by distinct microbial metabolic outputs in the blood.

  View details for DOI 10.1038/s42255-021-00348-0

  View details for Web of Science ID 000621880500014

  View details for PubMedID 33619379

  View details for PubMedCentralID PMC8169080

• Serum FSH Is Associated With BMD, Bone Marrow Adiposity, and Body Composition in the AGES-Reykjavik Study of Older Adults. The Journal of clinical endocrinology and metabolism Veldhuis-Vlug, A. G., Woods, G. N., Sigurdsson, S., Ewing, S. K., Le, P. T., Hue, T. F., Vittinghoff, E., Xu, K., Gudnason, V., Sigurdsson, G., Kado, D. M., Eiriksdottir, G., Harris, T., Schafer, A. L., Li, X., Zaidi, M., Rosen, C. J., Schwartz, A. V. 2021; 106 (3): e1156-e1169

  Abstract

  Follicle-stimulating hormone (FSH) concentrations increase during the perimenopausal transition and remain high after menopause. Loss of bone mineral density (BMD) and gain of bone marrow adiposity (BMA) and body fat mass also occur during this time. In mice, blocking the action of FSH increases bone mass and decreases fat mass.To investigate the associations between endogenous FSH levels and BMD, BMA, and body composition in older adults, independent of estradiol and testosterone levels.Older adults from the AGES-Reykjavik Study, an observational cohort study.Areal BMD, total body fat, and lean mass were measured with dual-energy x-ray absorptiometry. Lumbar vertebral BMA was measured by 1H-magnetic resonance spectroscopy. Volumetric BMD and visceral and subcutaneous adipose tissue (VAT, SAT) areas were measured with quantitative computed tomography. The least squares means procedure was used to determine sex hormone-adjusted associations between quartiles of serum FSH and BMD, BMA, and body composition.In women (N = 238, mean age 81 years), those in the highest FSH quartile, compared with the lowest quartile, had lower adjusted mean spine integral BMD (-8.6%), lower spine compressive strength index (-34.8%), higher BMA (+8.4%), lower weight (-8.4%), lower VAT (-17.6%), lower lean mass (-6.1%), and lower fat mass (-11.9%) (all P < 0.05). In men, FSH level was not associated with any outcome.Older postmenopausal women with higher FSH levels have higher BMA, but lower BMD and lower fat and lean mass, independent of estradiol and testosterone levels. Longitudinal studies are needed to better understand the underlying mechanisms.

  View details for DOI 10.1210/clinem/dgaa922

  View details for PubMedID 33326040

  View details for PubMedCentralID PMC7947831

• Association Between Variation in Red Cell Size and Multiple Aging-Related Outcomes. The journals of gerontology. Series A, Biological sciences and medical sciences Kim, K. M., Lui, L. Y., Browner, W. S., Cauley, J. A., Ensrud, K. E., Kado, D. M., Orwoll, E. S., Schousboe, J. T., Cummings, S. R. 2021; 76 (7): 1288-1294

  Abstract

  We tested whether greater variation in red blood cell size, measured by red cell distribution width (RDW), may predict aging-related degenerative conditions and therefore, serve as a marker of biological aging.Three thousand six hundred and thirty-five community-dwelling older men were enrolled in the prospective Osteoporotic Fractures in Men Study. RDW was categorized into 4 groups (≤13.0%, 13.1%-14.0%, 14.1%-15.0%, and ≥15.1%). Functional limitations, frailty, strength, physical performance, and cognitive function were measured at baseline and 7.4 years later. Falls were recorded in the year after baseline; hospitalizations were obtained for 2 years after baseline. Mortality was assessed during a mean of 8.3 years of follow-up.Participants with greater variability in red cell size were weaker, walked more slowly, and had a worse cognitive function. They were more likely to have functional limitations (35.2% in the highest RDW category vs 16.0% in the lowest, p < .001) and frailty (30.3% vs 11.3%, p < .001). Those with greater variability in red cell size were more likely to develop new functional limitations and to become frail. The risk of having 2 or more falls was also greater (highest 19.2% vs lowest 10.3%, p < .001). The risk of hospitalization was higher in those with the highest variability (odds ratio [95% confidence interval], 1.8 [1.3-2.5]) compared with the lowest. Variability in red cell size was related to total and cause-specific mortality.Greater variability in red cell size is associated with diverse aging-related outcomes, suggesting that it may have potential value as a marker for biological aging.

  View details for DOI 10.1093/gerona/glaa217

  View details for PubMedID 32894755

  View details for PubMedCentralID PMC8202142

• Individual and joint trajectories of change in bone, lean mass and physical performance in older men. BMC geriatrics Cawthon, P. M., Parimi, N., Langsetmo, L., Cauley, J. A., Ensrud, K. E., Cummings, S. R., Lane, N. E., Hoffman, A. R., Lapidus, J., Gill, T. M., McCulloch, C. E., Stefanick, M. L., Kado, D. M., Drieling, R., Orwoll, E. S. 2020; 20 (1): 161

  Abstract

  BACKGROUND: Declines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men.METHODS: Using repeated longitudinal data from up to four visits across 6.9years from up to 4681 men (mean age at baseline 72.7yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations.RESULTS: The patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data.CONCLUSIONS: Our description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.

  View details for DOI 10.1186/s12877-020-01560-5

  View details for PubMedID 32370738

• Vitamin D metabolites and the gut microbiome in older men. Nature communications Thomas, R. L., Jiang, L., Adams, J. S., Xu, Z. Z., Shen, J., Janssen, S., Ackermann, G., Vanderschueren, D., Pauwels, S., Knight, R., Orwoll, E. S., Kado, D. M. 2020; 11 (1): 5997

  Abstract

  The vitamin D receptor is highly expressed in the gastrointestinal tract where it transacts gene expression. With current limited understanding of the interactions between the gut microbiome and vitamin D, we conduct a cross-sectional analysis of 567 older men quantifying serum vitamin D metabolites using LC-MSMS and defining stool sub-Operational Taxonomic Units from16S ribosomal RNA gene sequencing data. Faith's Phylogenetic Diversity and non-redundant covariate analyses reveal that the serum 1,25(OH)2D level explains 5% of variance in α-diversity. In β-diversity analyses using unweighted UniFrac, 1,25(OH)2D is the strongest factor assessed, explaining 2% of variance. Random forest analyses identify 12 taxa, 11 in the phylum Firmicutes, eight of which are positively associated with either 1,25(OH)2D and/or the hormone-to-prohormone [1,25(OH)2D/25(OH)D] "activation ratio." Men with higher levels of 1,25(OH)2D and higher activation ratios, but not 25(OH)D itself, are more likely to possess butyrate producing bacteria that are associated with better gut microbial health.

  View details for DOI 10.1038/s41467-020-19793-8

  View details for PubMedID 33244003

  View details for PubMedCentralID PMC7693238

• Greater Bone Marrow Adiposity Predicts Bone Loss in Older Women. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Woods, G. N., Ewing, S. K., Sigurdsson, S., Kado, D. M., Eiriksdottir, G., Gudnason, V., Hue, T. F., Lang, T. F., Vittinghoff, E., Harris, T. B., Rosen, C., Xu, K., Li, X., Schwartz, A. V. 2020; 35 (2): 326-332

  Abstract

  Bone marrow adiposity (BMA) is associated with aging and osteoporosis, but whether BMA can predict bone loss and fractures remains unknown. Using data from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study, we investigated the associations between 1 H-MRS-based measures of vertebral bone marrow adipose tissue (BMAT), annualized change in bone density/strength by quantitative computed tomography (QCT) and DXA, and secondarily, with incident clinical fractures and radiographic vertebral fractures among older adults. The associations between BMAT and annualized change in bone density/strength were evaluated using linear regression models, adjusted for age, body mass index (BMI), diabetes, estradiol, and testosterone. Cox proportional hazards models were used to evaluate the associations between baseline BMAT and incident clinical fractures, and logistic regression models for incident vertebral fractures. At baseline, mean ± SD age was 80.9 ± 4.2 and 82.6 ± 4.2 years in women (n = 148) and men (n = 150), respectively. Mean baseline BMAT was 55.4% ± 8.1% in women and 54.1% ± 8.2% in men. Incident clinical fractures occurred in 7.4% of women over 2.8 years and in 6.0% of men over 2.2 years. Incident vertebral fractures occurred in 12% of women over 3.3 years and in 17% of men over 2.7 years. Each 1 SD increase in baseline BMAT was associated with a 3.9 mg2 /cm4 /year greater loss of spine compressive strength index (p value = .003), a 0.9 mg/cm3 /year greater loss of spine trabecular BMD (p value = .02), and a 1.2 mg/cm3 /year greater loss of femoral neck trabecular BMD (p value = .02) in women. Among men, there were no associations between BMAT and changes in bone density/strength. There were no associations between BMAT and incident fractures in women or men. In conclusion, we found greater BMAT is associated with greater loss of trabecular bone at the spine and femoral neck, and greater loss of spine compressive strength, in older women. © 2019 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.3895

  View details for PubMedID 31618468

• Age-associated changes in the mechanical properties of human cadaveric pelvic floor muscles. Journal of biomechanics Burnett, L. A., Cook, M., Shah, S., Michelle Wong, M., Kado, D. M., Alperin, M. 2020; 98: 109436

  Abstract

  Proper function of the female pelvic floor requires intact pelvic floor muscles (PFMs). The prevalence of pelvic floor disorders (PFDs) increases substantially with age, in part due to clinically identified deterioration of PFM function with age. However, the etiology of this decline remains largely unknown. We previously demonstrated that PFMs undergo age-related fibrotic changes. This study sought to determine whether aging also impacts PFMs' passive mechanical properties that are largely determined by the intramuscular extracellular matrix. Biopsies from younger (≤52y) and older (>52y) female cadaveric donors were procured from PFMs, specifically coccygeus (C) and two portions of the levator ani - iliococcygeus (IC) and pubovisceralis (PV), and the appendicular muscles - obturator internus (OI) and vastus lateralis (VL). Muscle bundles were subjected to a passive loading protocol, and stress-sarcomere length (Ls) relationships calculated. Muscle stiffness was compared between groups using 2-way ANOVA and Sidak pairwise comparisons, α < 0.05. The mean age was 43.4 ± 11.6y and 74.9 ± 11.9y in younger (N = 5) and older (N = 10) donors, respectively. In all PFMs, the quadratic coefficient of parabolic regression of the stress-Ls curve, a measure of stiffness, was lower in the younger versus older group: C: 33.7 ± 13.9 vs 87.2 ± 10.7, P = 0.02; IC: 38.3 ± 12.7 vs 84.5 ± 13.9, P = 0.04; PV: 24.7 ± 8.8 vs 74.6 ± 9.6, P = 0.04. In contrast, non-PFM stiffness was not affected by aging: OI: 14.5 ± 4.7 vs 32.9 ± 6.2, P = 0.8 and VL: 13.6 ± 5.7 vs 30.1 ± 5.3, P = 0.9. Age-associated increase in PFM stiffness is predicted to negatively impact PFM function by diminishing muscle load-bearing, excursional, contractile, and regenerative capacity, thus predisposing older women to PFDs.

  View details for DOI 10.1016/j.jbiomech.2019.109436

  View details for PubMedID 31708240

  View details for PubMedCentralID PMC6956987

• Response to: Some Questions About the Article "The Efficacy and Safety of Vertebral Augmentation: A Second ASBMR Task Force Report". Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Buchbinder, R., Ebeling, P. R., Akesson, K., Bauer, D. C., Eastell, R., Fink, H. A., Giangregorio, L., Guanabens, N., Kado, D., Kallmes, D., Katzman, W., Rodriguez, A., Wermers, R., Wilson, H. A., Bouxsein, M. L. 2020; 35 (1): 212-213

  View details for DOI 10.1002/jbmr.3906

  View details for PubMedID 31743502

• Associations between novel jump test measures, grip strength, and physical performance: the Osteoporotic Fractures in Men (MrOS) Study. Aging clinical and experimental research Winger, M. E., Caserotti, P., Cauley, J. A., Boudreau, R. M., Piva, S. R., Cawthon, P. M., Harris, T. B., Barrett-Connor, E., Fink, H. A., Kado, D. M., Strotmeyer, E. S. 2020; 32 (4): 587-595

  Abstract

  Weight-bearing jump tests measure lower extremity muscle power, velocity, and force, and may be more strongly related to physical performance than grip strength. However, these relationships are not well described in older adults.Participants were 1242 older men (mean age 84 ± 4 years) in the Osteoporotic Fractures in Men (MrOS) Study. Jump peak power (Watts/kg body weight), force (Newton/kg body weight) at peak power, and velocity (m/s) at peak power were measured by jump tests on a force plate. Grip strength (kg/kg body weight) was assessed by hand-held dynamometry. Physical performance included 400 m walk time (s), 6 m usual gait speed (m/s), and 5-repeated chair stands speed (#/s).In adjusted Pearson correlations, power/kg and velocity moderately correlated with all performance measures (range r = 0.41-0.51; all p < 0.001), while correlations for force/kg and grip strength/kg were weaker (range r = 0.20-0.33; all p < 0.001). Grip strength/kg moderately correlated with power/kg (r = 0.44; p < 0.001) but not velocity or force/kg. In adjusted linear regression with standardized βs, 1 SD lower power/kg was associated with worse: 400 m walk time (β = 0.47), gait speed (β = 0.42), and chair stands speed (β = 0.43) (all p < 0.05). Associations with velocity were similar (400 m walk time: β = 0.42; gait speed: β = 0.38; chair stands speed: β = 0.37; all p < 0.05). Force/kg and grip strength/kg were more weakly associated with performance (range β = 0.18-0.28; all p < 0.05).Jump power and velocity had stronger associations with physical performance than jump force or grip strength. This suggests lower extremity power and velocity may be more strongly related to physical performance than lower extremity force or upper extremity strength in older men.

  View details for DOI 10.1007/s40520-019-01421-1

  View details for PubMedID 31853832

  View details for PubMedCentralID PMC7716274

• Comparing Analytical Methods for the Gut Microbiome and Aging: Gut Microbial Communities and Body Weight in the Osteoporotic Fractures in Men (MrOS) Study. The journals of gerontology. Series A, Biological sciences and medical sciences Shardell, M., Parimi, N., Langsetmo, L., Tanaka, T., Jiang, L., Orwoll, E., Shikany, J. M., Kado, D. M., Cawthon, P. M. 2020; 75 (7): 1267-1275

  Abstract

  Determining the role of gut microbial communities in aging-related phenotypes, including weight loss, is an emerging gerontology research priority. Gut microbiome datasets comprise relative abundances of microbial taxa that necessarily sum to 1; analysis ignoring this feature may produce misleading results. Using data from the Osteoporotic Fractures in Men (MrOS) study (n = 530; mean [SD] age = 84.3 [4.1] years), we assessed 163 genera from stool samples and body weight. We compared conventional analysis, which does not address the sum-to-1 constraint, to compositional analysis, which does. Specifically, we compared elastic net regression (for variable selection) and conventional Bayesian linear regression (BLR) and network analysis to compositional BLR and network analysis; adjusting for past weight, height, and other covariates. Conventional BLR identified Roseburia and Dialister (higher weight) and Coprococcus-1 (lower weight) after multiple comparisons adjustment (p < .0125); plus Sutterella and Ruminococcus-1 (p < .05). No conventional network module was associated with weight. Using compositional BLR, Coprococcus-2 and Acidaminococcus were most strongly associated with higher adjusted weight; Coprococcus-1 and Ruminococcus-1 were most strongly associated with lower adjusted weight (p < .05), but nonsignificant after multiple comparisons adjustment. Two compositional network modules with respective hub taxa Blautia and Faecalibacterium were associated with adjusted weight (p < .01). Findings depended on analytical workflow. Compositional analysis is advocated to appropriately handle the sum-to-1 constraint.

  View details for DOI 10.1093/gerona/glaa034

  View details for PubMedID 32025711

  View details for PubMedCentralID PMC7447861

• Kyphosis and 3-year fall risk in community-dwelling older men. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA McDaniels-Davidson, C., Nichols, J. F., Vaida, F., Marshall, L. M., Kado, D. M. 2020; 31 (6): 1097-1104

  Abstract

  Hyperkyhosis is thought to be a fall risk factor in older adults. This large study of older men found that fall risk increased with greater kyphosis measured with the blocks method, but did not find an association between kyphosis and falls when measured by the commonly used the Cobb angle method.Research suggests an association between hyperkyphosis and falls in community-dwelling older adults, though this has not been investigated within large, population-based studies. This study sought to determine whether two measures of kyphosis prospectively predict fall risk over 3 years among older men.Within the Osteoporotic Fractures in Men Study (MrOS), we conducted two 3-year prospective studies of 2346 and 2928 men. The first group had kyphosis measured by the Cobb angle at visit 1, while the second group had kyphosis assessed with the blocks method at visit 3; both groups then self-reported falls tri-annually for 3 years. Poisson regression with GEE was used to obtain relative risks (RR) of falls.The fall rates over 3 years were 651/1000 person-years among the visit 1 sample (mean age 74 ± 6 years) and 839/1000 person-years among the visit 3 sample (mean age 79 ± 5 years). In adjusted models of the visit 3 sample, the risk of falls was increased by 12% for each standard deviation increase (1.4 blocks) in the number of blocks required to achieve a neutral head and neck position (RR = 1.12, 95% CI = 1.06, 1.18). The Cobb angle was not associated with falls in the visit 1 sample.Although the Cobb angle did not predict falls in community-dwelling older men over 3 years, the blocks method of measuring kyphosis was predictive of falls in this population. This difference could be due to the Cobb angle's focus on thoracic kyphosis, whereas the blocks method may additionally capture abnormal cervical spine curvature.

  View details for DOI 10.1007/s00198-019-05155-8

  View details for PubMedID 32040599

  View details for PubMedCentralID PMC7444683

• Hyperkyphosis and self-reported and objectively measured sleep quality in older men. PloS one Kaufmann, C. N., Shen, J., Woods, G. N., Lane, N. E., Stone, K. L., Kado, D. M. 2020; 15 (2): e0228638

  Abstract

  Hyperkyphosis is associated with restricted pulmonary function and posture, potentially contributing to poor sleep. A previous study reported older women with hyperkyphosis had worse self-reported sleep quality, but it is less clear if this association exists in men. We examined the association between hyperkyphosis and subjective and objective sleep quality in a cohort of older men.Longitudinal analysis of data from large cohort of older men participating in the Osteoporotic Fractures in Men Study (MrOS).Community.We studied 754 men participants in MrOS who had kyphosis measured during the 3rd clinic visit (2007-2009) and future subjective and objective sleep quality assessed between 2009-2012 (an average of 2.9 years later).N/A.To measure kyphosis, 1.7 cm thick wooden blocks were placed under the participant's head to achieve a neutral spine position while lying supine on a DXA table. We collected data on both subjective (Pittsburgh Sleep Quality Index [PSQI], and Epworth Sleepiness Scale [ESS]) and objective (wrist actigraphy: Total Sleep Time [TST], Wake After Sleep Onset [WASO], Sleep Efficiency [SE], Sleep Onset Latency [SOL]; and polysomnography: Apnea Hypopnea Index [AHI]) sleep measurements. Those who required >3 blocks were considered hyperkyphotic (n = 145 or 19.2%).In unadjusted and multivariable analyses, men with hyperkyphosis did not report having worse self-reported sleep characteristics based on PSQI and ESS. Similarly, there were no significant associations between hyperkyphosis and objective sleep measures. When examined as a continuous predictor (blocks ranging from 0-8), results were no different.Although we hypothesized that poor posture in those with hyperkyphosis would interfere with sleep, in this sample of older men, worse kyphosis was not associated with self-reported or objectively measured poor sleep quality.

  View details for DOI 10.1371/journal.pone.0228638

  View details for PubMedID 32045440

  View details for PubMedCentralID PMC7012394

• Factors Associated With Kyphosis and Kyphosis Progression in Older Men: The MrOS Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Woods, G. N., Huang, M. H., Lee, J. H., Cawthon, P. M., Fink, H. A., Schousboe, J. T., Kado, D. M. 2020; 35 (11): 2193-2198

  Abstract

  Hyperkyphosis (HK), or increased anterior curvature of the thoracic spine, is common in older persons. Although it is thought that vertebral fractures are the major cause of HK, only about a third of those with the worst degrees of kyphosis have underlying vertebral fractures. In older men, HK is associated with increased risk of poor physical function, injurious falls, and earlier mortality, but its causes are not well understood. We studied 1092 men from the Osteoporotic Fractures in Men (MrOS) Study aged 64 to 92 years (mean age 72.8 years) who had repeated standardized radiographic measures of Cobb angle of kyphosis to identify risk factors for HK (defined as ≥50 degrees) and kyphosis progression over an interval of 4.7 years. Specifically, we examined the associations with age, body mass index (BMI), weight, weight loss, health behaviors, family history of HK, muscle strength, degenerative disc disease (DDD), bone mineral density (BMD), prevalent thoracic vertebral fractures, and incident thoracic vertebral fractures (longitudinal analyses only). Men had an average baseline kyphosis of 38.9 (standard deviation [SD] 11.4) degrees. Fifteen percent had HK (n = 161) with a mean Cobb angle of 56.7 (SD = 6.0) degrees; these men were older (p < 0.01), had lower BMI (p < 0.01), lower BMD (p < 0.01), were more likely to have family history of HK (p = 0.01), and prevalent thoracic vertebral fracture (p < 0.01) compared with the men without HK. During follow-up, men experienced an average of 1.4 degrees of kyphosis progression with DDD (p = 0.04) and lower hip BMD (p < 0.01) being identified as statistically significant and incident vertebral fractures (p = 0.05) nearly significant factors associated with worse progression. These results suggest that in older men, HK results from not only low BMD and vertebral fractures but that DDD also may play a significant role in kyphosis progression. © 2020 American Society for Bone and Mineral Research (ASBMR).

  View details for DOI 10.1002/jbmr.4123

  View details for PubMedID 32615004

• Handwashing and Detergent Treatment Greatly Reduce SARS-CoV-2 Viral Load on Halloween Candy Handled by COVID-19 Patients. mSystems Salido, R. A., Morgan, S. C., Rojas, M. I., Magallanes, C. G., Marotz, C., DeHoff, P., Belda-Ferre, P., Aigner, S., Kado, D. M., Yeo, G. W., Gilbert, J. A., Laurent, L., Rohwer, F., Knight, R. 2020; 5 (6)

  Abstract

  Due to the COVID-19 pandemic and potential public health implications, we are publishing this peer-reviewed manuscript in its accepted form. The final, copyedited version of the paper will be available at a later date. Although SARS-CoV-2 is primarily transmitted by respiratory droplets and aerosols, transmission by fomites remains plausible. During Halloween, a major event for children in numerous countries, SARS-CoV-2 transmission risk via candy fomites worries many parents. To address this concern, we enrolled 10 recently diagnosed asymptomatic or mildly/moderately symptomatic COVID-19 patients to handle typical Halloween candy (pieces individually wrapped) under three conditions: normal handling with unwashed hands, deliberate coughing and extensive touching, and normal handling following handwashing. We then used a factorial design to subject the candies to two post-handling treatments: no washing (untreated) and household dishwashing detergent. We measured SARS-CoV-2 load by RT-qPCR and LAMP. From the candies not washed post-handling, we detected SARS-CoV-2 on 60% of candies that were deliberately coughed on, 60% of candies normally handled with unwashed hands, but only 10% of candies handled after hand washing. We found that treating candy with dishwashing detergent reduced SARS-CoV-2 load by 62.1% in comparison to untreated candy. Taken together, these results suggest that although the risk of transmission of SARS-CoV-2 by fomites is low even from known COVID-19 patients, viral RNA load can be reduced to near zero by the combination of handwashing by the infected patient and ≥1 minute detergent treatment after collection. We also found that the inexpensive and fast LAMP protocol was more than 80% concordant with RT-qPCR.IMPORTANCE The COVID-19 pandemic is leading to important tradeoffs between risk of SARS-CoV-2 transmission and mental health due to deprivation from normal activities, with these impacts being especially profound in children. Due to the ongoing pandemic, Halloween activities will be curtailed as a result of the concern that candy from strangers might act as fomites. Here we demonstrate that these risks can be mitigated by ensuring that prior to handling candy, the candy giver washes their hands, and by washing collected candy with household dishwashing detergent. Even in the most extreme case, with candy deliberately coughed on by known COVID-19 patients, viral load was reduced dramatically after washing with household detergent. We conclude that with reasonable precautions, even if followed only by either the candy giver or the candy recipient, the risk of viral transmission by this route is very low.

  View details for DOI 10.1128/mSystems.01074-20

  View details for PubMedID 33127739

  View details for PubMedCentralID PMC7743156

• Association of dietary patterns with the gut microbiota in older, community-dwelling men. The American journal of clinical nutrition Shikany, J. M., Demmer, R. T., Johnson, A. J., Fino, N. F., Meyer, K., Ensrud, K. E., Lane, N. E., Orwoll, E. S., Kado, D. M., Zmuda, J. M., Langsetmo, L. 2019; 110 (4): 1003-1014

  Abstract

  While the gut microbiota is relatively stable through adulthood, its composition is influenced by various host and environmental factors, including changes in health, gastrointestinal processes (e.g., transit time, gastric acidity), medication use, and diet. The association of habitual diet, in the form of a posteriori-derived dietary patterns, and microbiota composition has not been adequately studied, particularly in older men.The objective was to investigate the association of dietary patterns with the composition and diversity of the gut bacterial microbiota in community-dwelling, older men.This cross-sectional study included 517 men who were participants in the Osteoporotic Fractures in Men (MrOS) Study (≥65 y of age at baseline in 2000-2002) and who provided a stool sample and completed an FFQ at MrOS Visit 4 in 2014-2016. Dietary patterns were derived by factor analysis. 16S ribosomal RNA target gene sequencing was performed and taxonomy assignments were derived using the Greengenes database. Linear regression and permutational multivariate analysis of variance (PERMANOVA) considered variations in alpha and beta diversity by dietary pattern, and a model that implements a 0-inflated Gaussian distribution of mean group abundance for each taxa (metagenomeSeq) assessed taxonomic variations by dietary pattern.In multivariable-adjusted models, greater adherence to the Western pattern was positively associated with families Mogibacteriaceae and Veillonellaceae and genera Alistipes, Anaerotruncus, CC-115, Collinsella, Coprobacillus, Desulfovibrio, Dorea, Eubacterium, and Ruminococcus, while greater adherence to the prudent pattern was positively associated with order Streptophyta, family Victivallaceae, and genera Cetobacterium, Clostridium, Faecalibacterium, Lachnospira, Paraprevotella, and Veillonella. The relative abundance of the dominant gut bacterial phyla, Bacteroidetes and Firmicutes, did not differ between participants with greater adherence to the Western pattern, compared with those with greater adherence to the prudent pattern. Dietary patterns were not associated with measures of alpha diversity, but beta diversity measures were significantly associated with both Western and prudent patterns.We observed significant associations between dietary patterns and measures of gut microbial composition in this sample of community-dwelling, older men.

  View details for DOI 10.1093/ajcn/nqz174

  View details for PubMedID 31504105

  View details for PubMedCentralID PMC6766444

• Breast cancer treatment and its effects on aging. Journal of geriatric oncology Chang, L., Weiner, L. S., Hartman, S. J., Horvath, S., Jeste, D., Mischel, P. S., Kado, D. M. 2019; 10 (2): 346-355

  Abstract

  Breast cancer is the most common cancer of women in the United States. It is also proving to be one of the most treatable. Early detection, surgical intervention, therapeutic radiation, cytotoxic chemotherapies and molecularly targeted agents are transforming the lives of patients with breast cancer, markedly improving their survival. Although current breast cancer treatments are largely successful in producing cancer remission and extending lifespan, there is concern that these treatments may have long lasting detrimental effects on cancer survivors, in part, through their impact on non-tumor cells. Presently, the impact of breast cancer treatment on normal cells, its impact on cellular function and its effect on the overall function of the individual are incompletely understood. In particular, it is unclear whether breast cancer and/or its treatments are associated with an accelerated aging phenotype. In this review, we consider breast cancer survivorship from the perspective of accelerated aging, and discuss the evidence suggesting that women treated for breast cancer may suffer from an increased rate of physical and cognitive decline that likely corresponds with underlying vulnerabilities of genome instability, epigenetic changes, and cellular senescence.

  View details for DOI 10.1016/j.jgo.2018.07.010

  View details for PubMedID 30078714

  View details for PubMedCentralID PMC7062379

• Temporal stability of urinary cadmium in samples collected several years apart in a population of older persons. International journal of hygiene and environmental health Meliker, J. R., Vacchi-Suzzi, C., Harrington, J., Levine, K., Lui, L. Y., Bauer, D. C., Orwoll, E., Kado, D. M. 2019; 222 (2): 230-234

  Abstract

  There is growing evidence that urine cadmium is a temporally stable biomarker indicative of long-term cadmium exposure; however questions remain with regard to generalizability to older persons, the impact of changes in smoking behavior, and the degree of temporal stability when repeat sample collection spans years instead of weeks or months.Using archived samples from cohorts of older men (Osteoporotic Fractures in Men (MrOS-US)) and women (Study of Osteoporotic Fractures (SOF)) (mean age = 80 at study visit 2), we analyzed two morning urine samples each from 39 men and 18 women with a diverse self-reported smoking history. For MrOS, samples were collected approximately 6 years apart, and 4 years apart for SOF. Intra-class correlations were computed to assess temporal stability, and adjusted for age and body mass index.The median creatinine-adjusted urinary cadmium levels (0.39 μg/g for men, 0.89 μg/g for women) were similar to levels expected for these age/sex groups in the US according to the National Health and Nutrition Examination Survey. The overall intra-class correlation was high (ICC = 0.85; 95% CI: 0.76-0.91) and similar between cohorts (MrOS: ICC = 0.74; 95% CI: 0.58-0.86; SOF: ICC = 0.81; 95% CI: 0.59-0.93), but slightly lower among those who stopped smoking between visits of sample collection (ICC = 0.64; 95% CI: 0.31-0.87) or among former smokers who quit prior to the first sample collection (ICC = 0.68; 95% CI: 0.25-0.93).We report good-to-excellent reproducibility of urine cadmium using morning urine samples collected 4-6 years apart from older men and women, but slightly lower correlations among those with a history of smoking. Single measures of urine cadmium are a reliable biomarker in older men and women.

  View details for DOI 10.1016/j.ijheh.2018.10.005

  View details for PubMedID 30401599

  View details for PubMedCentralID PMC6408983

• The Efficacy and Safety of Vertebral Augmentation: A Second ASBMR Task Force Report. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Ebeling, P. R., Akesson, K., Bauer, D. C., Buchbinder, R., Eastell, R., Fink, H. A., Giangregorio, L., Guanabens, N., Kado, D., Kallmes, D., Katzman, W., Rodriguez, A., Wermers, R., Wilson, H. A., Bouxsein, M. L. 2019; 34 (1): 3-21

  Abstract

  Vertebral augmentation is among the current standards of care to reduce pain in patients with vertebral fractures (VF), yet a lack of consensus regarding efficacy and safety of percutaneous vertebroplasty and kyphoplasty raises questions on what basis clinicians should choose one therapy over another. Given the lack of consensus in the field, the American Society for Bone and Mineral Research (ASBMR) leadership charged this Task Force to address key questions on the efficacy and safety of vertebral augmentation and other nonpharmacological approaches for the treatment of pain after VF. This report details the findings and recommendations of this Task Force. For patients with acutely painful VF, percutaneous vertebroplasty provides no demonstrable clinically significant benefit over placebo. Results did not differ according to duration of pain. There is also insufficient evidence to support kyphoplasty over nonsurgical management, percutaneous vertebroplasty, vertebral body stenting, or KIVA®. There is limited evidence to determine the risk of incident VF or serious adverse effects (AE) related to either percutaneous vertebroplasty or kyphoplasty. No recommendation can be made about harms, but they cannot be excluded. For patients with painful VF, it is unclear whether spinal bracing improves physical function, disability, or quality of life. Exercise may improve mobility and may reduce pain and fear of falling but does not reduce falls or fractures in individuals with VF. General and intervention-specific research recommendations stress the need to reduce study bias and address methodological flaws in study design and data collection. This includes the need for larger sample sizes, inclusion of a placebo control, more data on serious AE, and more research on nonpharmacologic interventions. Routine use of vertebral augmentation is not supported by current evidence. When it is offered, patients should be fully informed about the evidence. Anti-osteoporotic medications reduce the risk of subsequent vertebral fractures by 40-70%. © 2018 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.3653

  View details for PubMedID 30677181

• Correlates of T50 and relationships with bone mineral density in community-living older men: the osteoporotic fractures in men (MrOS) study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA Bullen, A. L., Anderson, C. A., Hooker, E. R., Kado, D. M., Orwoll, E., Pasch, A., Ix, J. H. 2019

  Abstract

  T50 is a novel serum-based marker that assesses the propensity of calcification in serum. Shorter T50 indicates greater propensity to calcify and it has been associated to cardiovascular disease (CVD) and mortality among patients with kidney disease. In the general population, neither the correlates of T50 nor the relationships of T50 with bone mineral density (BMD) are known.We performed a nested cross-sectional study selecting 150 individuals at random among participants from the Osteoporotic Fractures in Men (MrOS) Study, a study of community-living older men. We categorized individuals into tertiles of T50 and compared demographics and disease indicators across tertiles. We utilized linear regression to evaluate the cross-sectional association between T50 and hip and spine BMD in multivariable models.Older age was associated with shorter T50. Kidney function tended to be lower in those with shorter T50 and the prevalence of CVD and peripheral arterial disease in those with shorter T50, albeit these findings did not achieve statistical significance. We found no statistically significant associations between T50 and total hip or total spine BMD in either unadjusted or multivariable adjusted models.T50, a novel indicator of serum calcification propensity, is not associated with BMD in community-living older men. Future larger studies should determine if T50 may give insights to CVD in the general population above and beyond traditional risk factors.

  View details for DOI 10.1007/s00198-019-04925-8

  View details for PubMedID 30887076

• Strong Relation between Muscle Mass Determined by D3-creatine Dilution, Physical Performance and Incidence of Falls and Mobility Limitations in a Prospective Cohort of Older Men. The journals of gerontology. Series A, Biological sciences and medical sciences Cawthon, P. M., Orwoll, E. S., Peters, K. E., Ensrud, K. E., Cauley, J. A., Kado, D. M., Stefanick, M. L., Shikany, J. M., Strotmeyer, E. S., Glynn, N. W., Caserotti, P. n., Shankaran, M. n., Hellerstein, M. n., Cummings, S. R., Evans, W. J. 2018

  Abstract

  Direct assessment of skeletal muscle mass in older adults is clinically challenging. Relationships between lean mass and late-life outcomes have been inconsistent. The D3-creatine dilution method provides a direct assessment of muscle mass.Muscle mass was assessed by D3-creatine (D3Cr) dilution in 1,382 men (mean age, 84.2 yrs). Participants completed the Short Physical Performance Battery (SPPB); usual walking speed (6 meters); and DXA lean mass. Men self-reported mobility limitations (difficulty walking 2-3 blocks or climbing 10 steps); recurrent falls (2+); and serious injurious falls in the subsequent year. Across quartiles of D3Cr muscle mass/body mass, multivariate linear models calculated means for SPPB and gait speed; multivariate logistic models calculated odds ratios for incident mobility limitations or falls.Compared to men in the highest quartile, those in the lowest quartile of D3Cr muscle mass/body mass had slower gait speed (Q1: 1.04 vs Q4: 1.17 m/s); lower SPPB (Q1: 8.4 vs Q4: 10.4 points); greater likelihood of incident serious injurious falls (OR Q1 vs Q4: 2.49, 95% CI: 1.37, 4.54); prevalent mobility limitation (OR Q1 vs Q4,: 6.1, 95%CI: 3.7, 10.3) and incident mobility limitation (OR Q1 vs Q4: 2.15 95% CI: 1.42, 3.26); p for trend <.001 for all. Results for incident recurrent falls were in the similar direction (p=0.156). DXA lean mass had weaker associations with the outcomes.Unlike DXA lean mass, low D3Cr muscle mass/body mass is strongly related to physical performance, mobility and incident injurious falls in older me.

  View details for PubMedID 29897420

• Kyphosis and incident falls among community-dwelling older adults. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA McDaniels-Davidson, C., Davis, A., Wing, D., Macera, C., Lindsay, S. P., Schousboe, J. T., Nichols, J. F., Kado, D. M. 2018; 29 (1): 163-169

  Abstract

  Hyperkyphosis commonly affects older persons and is associated with morbidity and mortality. Many have hypothesized that hyperkyphosis increases fall risk. Within this prospective study of older adults, kyphosis was significantly associated with incident falls over 1 year. Measures of hyperkyphosis could enhance falls risk assessments during primary care office visits.To determine the association between four measures of kyphosis and incident and injurious falls in older persons.Community-dwelling adults aged 65 and older (n = 72) residing in southern California were invited to participate in a prospective cohort study. Participants had kyphosis assessed four ways. Two standing measures included a flexicurve ruler placed against the back to derive a kyphotic index and the Debrunner kyphometer, a protractor used to measure the kyphotic angle in degrees. Two lying measures included the blocks method (number of 1.7 cm blocks needed to achieve a neutral head position while lying supine) and traditional Cobb angle calculation derived from DXA based lateral vertebral assessment. Baseline demographic, clinical, and other health information (including a timed up and go (TUG) test) were assessed at a clinic visit. Participants were followed monthly through email or postcard for 1 year, with falls outcomes confirmed through telephone interview.Mean age was 77.8 (± 7.1) among the 52 women and 20 men. Over 12 months, 64% of participants experienced at least one incident fall and 35% experienced an injurious fall. Each standard deviation increase in kyphosis resulted in more than doubling the adjusted odds of an incident fall, even after adjusting for TUG. Odds of injurious falls were less consistent across measures; after adjusting for TUG, only the blocks method was associated with injurious falls.Each kyphosis measure was independently associated with incident falls. Findings were inconsistent for injurious falls; the blocks measure suggested the strongest association. If these findings are replicated, the blocks measure could be incorporated into office visits as a quick and efficient tool to identify patients at increased fall risk.

  View details for DOI 10.1007/s00198-017-4253-3

  View details for PubMedID 29018904

• Which Sleep Health Characteristics Predict All-Cause Mortality in Older Men? An Application of Flexible Multivariable Approaches. Sleep Wallace, M. L., Stone, K., Smagula, S. F., Hall, M. H., Simsek, B., Kado, D. M., Redline, S., Vo, T. N., Buysse, D. J. 2018; 41 (1)

  Abstract

  Sleep is multidimensional, with domains including duration, timing, continuity, regularity, rhythmicity, quality, and sleepiness/alertness. Individual sleep characteristics representing these domains are known to predict health outcomes. However, most studies consider sleep characteristics in isolation, resulting in an incomplete understanding of which sleep characteristics are the strongest predictors of health outcomes. We applied three multivariable approaches to robustly determine which sleep characteristics increase mortality risk in the osteoporotic fractures in men sleep study.In total, 2,887 men (mean 76.3 years) completed relevant assessments and were followed for up to 11 years. One actigraphy or self-reported sleep characteristic was selected to represent each of seven sleep domains. Multivariable Cox models, survival trees, and random survival forests were applied to determine which sleep characteristics increase mortality risk.Rhythmicity (actigraphy pseudo-F statistic) and continuity (actigraphy minutes awake after sleep onset) were the most robust sleep predictors across models. In a multivariable Cox model, lower rhythmicity (hazard ratio, HR [95%CI] =1.12 [1.04, 1.22]) and lower continuity (1.16 [1.08, 1.24]) were the strongest sleep predictors. In the random survival forest, rhythmicity and continuity were the most important individual sleep characteristics (ranked as the sixth and eighth most important among 43 possible sleep and non-sleep predictors); moreover, the predictive importance of all sleep information considered simultaneously followed only age, cognition, and cardiovascular disease.Research within a multidimensional sleep health framework can jumpstart future research on causal pathways linking sleep and health, new interventions that target specific sleep health profiles, and improved sleep screening for adverse health outcomes.

  View details for DOI 10.1093/sleep/zsx189

  View details for PubMedID 29165696

  View details for PubMedCentralID PMC5806578

• Sex hormones are negatively associated with vertebral bone marrow fat. Bone Mistry, S. D., Woods, G. N., Sigurdsson, S., Ewing, S. K., Hue, T. F., Eiriksdottir, G., Xu, K., Hilton, J. F., Kado, D. M., Gudnason, V., Harris, T. B., Rosen, C. J., Lang, T. F., Li, X., Schwartz, A. V. 2018; 108: 20-24

  Abstract

  Higher bone marrow fat (BMF)1 is associated with osteoporosis and reduced hematopoiesis. Exogenous estradiol reduces BMF in older women, but effects of endogenous sex hormones are unknown.To determine if endogenous sex hormones are associated with BMF in older men and women.Cross-sectional study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Participants using medications that may affect BMF were excluded.Vertebral BMF was measured with magnetic resonance spectroscopy. Estradiol, testosterone and sex hormone binding globulin were measured on archived serum. Linear regression models were adjusted for age, total percent body fat and visit window.Analyses included 244 men and 226 women, mean age 81.5 (SD 4.1) years. Mean BMF was 54.1% (SD 8.6) (men) and 54.7% (SD 8.1) (women). In adjusted models, per 1pg/ml increase in total estradiol, there was a statistically significant 0.26% decrease in BMF in men (95% CI: -0.41, -0.11) and a non-significant 0.20% decrease in women (95% CI: -0.55, 0.15), with no evidence of interaction by gender (p=0.88). Per 10ng/dl increase in total testosterone, there was a significant 0.10% decrease in BMF in men (95% CI: -0.17, -0.03) and a non-significant 0.13% (95% CI: -0.79, 0.53) decrease in women, with no evidence of interaction by gender (p=0.97).Higher bone marrow fat is associated with lower total estradiol and testosterone levels in older men, with a similar but statistically non-significant association in older women. Sex hormone levels appear to play a role in the regulation of bone marrow fat in older adults.

  View details for DOI 10.1016/j.bone.2017.12.009

  View details for PubMedID 29241825

  View details for PubMedCentralID PMC5803453

• Associations of recent weight loss with health care costs and utilization among older women. PloS one Schousboe, J. T., Kats, A. M., Langsetmo, L., Taylor, B. C., Vo, T. N., Kado, D. M., Fink, H. A., Ensrud, K. E. 2018; 13 (1): e0191642

  Abstract

  The association of weight loss with health care costs among older women is uncertain. Our study aim was to examine the association of objectively measured weight change with subsequent total health care (THC) costs and other health care utilization among older women. Our study population included 2,083 women (mean age 80.2 years) enrolled in the Study of Osteoporotic Fractures and U.S. Medicare Fee for Service. Weight loss and gain were defined, respectively, as ≥5% decrease and ≥5% increase in body weight, and weight maintenance as <5% change in body weight over a period of 4.5 years. THC costs, outpatient costs, hospitalizations, and skilled nursing facility [SNF] utilization were estimated from Medicare claims for 1 year after the period during which weight change was measured. The associations of weight change with THC and outpatient costs were estimated using generalized linear models with gamma variance and log link functions, and with hospitalizations and SNF utilization using logistic models. Adjusted for age and current body mass index (BMI), weight loss compared with weight maintenance was associated with a 35% increase in THC costs ($2148 [95% CI, 745 to 3552], 2014 U.S. dollars), a 15% increase in outpatient costs ($329 [95% C.I. -1 to 660]), and odds ratios of 1.42 (95% CI, 1.14 to 1.76) for ≥1 hospital stay and 1.45 (95% CI, 1.03 to 2.03) for ≥1 SNF stay. These associations did not vary by BMI category. After additional adjustment for multi-morbidity and functional status, associations of weight loss with all four outcomes were no longer significant. In conclusion, ≥5% weight loss among older women is not associated with increased THC and outpatient costs, hospitalization, and SNF utilization, irrespective of BMI category after accounting for multi-morbidity and impaired functional status that accompany weight loss.

  View details for DOI 10.1371/journal.pone.0191642

  View details for PubMedID 29377919

  View details for PubMedCentralID PMC5788355

• Patterns of menopausal hormone therapy use and hyperkyphosis in older women. Menopause (New York, N.Y.) Woods, G. N., Huang, M. H., Cawthon, P. M., McDaniels-Davidson, C., Fink, H. A., Kado, D. M. 2018; 25 (7): 738-743

  Abstract

  Hyperkyphosis, an exaggerated anterior curvature of the thoracic spine, is associated with poor physical function, falls, fractures, and earlier mortality. Low bone mineral density, bone loss, and vertebral fractures are strong risk factors for hyperkyphosis. Menopausal hormone therapy (HT) reverses bone loss, prevents vertebral fractures, and, therefore, we hypothesize, may reduce the risk for developing hyperkyphosis.We evaluated the cross-sectional association between Cobb angle of kyphosis from lateral spine radiographs and pattern of self-reported HT use during the prior 15-year period in 1,063 women from the Study of Osteoporotic Fractures.Participants had a mean age of 83.7 ± 3.3 years and a mean Cobb angle of 51.3 ± 14.6°. Forty-six per cent of women were characterized as never-users of HT, 24% as remote past users, 17% as intermittent users, and 12% as continuous users. In minimally adjusted models, the mean Cobb angle was 4.0° less in continuous HT users compared with never-users (P = 0.01); however, in fully adjusted models, this association was attenuated to 2.8° (P = 0.06). Remote past HT users had 3.0° less kyphosis compared with never-users in minimally adjusted models (P = 0.01), attenuated to 2.8° less in fully adjusted models (P = 0.02). Intermittent users did not differ from never-users in degree of kyphosis.Women reporting continuous or remote past HT use had less pronounced kyphosis than never-users by their mid-eighties, suggesting a possible role for HT in the prevention of age-related hyperkyphosis.

  View details for DOI 10.1097/GME.0000000000001070

  View details for PubMedID 29462096

  View details for PubMedCentralID PMC6014891

• Phylogenetic Placement of Exact Amplicon Sequences Improves Associations with Clinical Information. mSystems Janssen, S., McDonald, D., Gonzalez, A., Navas-Molina, J. A., Jiang, L., Xu, Z. Z., Winker, K., Kado, D. M., Orwoll, E., Manary, M., Mirarab, S., Knight, R. 2018; 3 (3)

  Abstract

  Recent algorithmic advances in amplicon-based microbiome studies enable the inference of exact amplicon sequence fragments. These new methods enable the investigation of sub-operational taxonomic units (sOTU) by removing erroneous sequences. However, short (e.g., 150-nucleotide [nt]) DNA sequence fragments do not contain sufficient phylogenetic signal to reproduce a reasonable tree, introducing a barrier in the utilization of critical phylogenetically aware metrics such as Faith's PD or UniFrac. Although fragment insertion methods do exist, those methods have not been tested for sOTUs from high-throughput amplicon studies in insertions against a broad reference phylogeny. We benchmarked the SATé-enabled phylogenetic placement (SEPP) technique explicitly against 16S V4 sequence fragments and showed that it outperforms the conceptually problematic but often-used practice of reconstructing de novo phylogenies. In addition, we provide a BSD-licensed QIIME2 plugin (https://github.com/biocore/q2-fragment-insertion) for SEPP and integration into the microbial study management platform QIITA. IMPORTANCE The move from OTU-based to sOTU-based analysis, while providing additional resolution, also introduces computational challenges. We demonstrate that one popular method of dealing with sOTUs (building a de novo tree from the short sequences) can provide incorrect results in human gut metagenomic studies and show that phylogenetic placement of the new sequences with SEPP resolves this problem while also yielding other benefits over existing methods.

  View details for DOI 10.1128/mSystems.00021-18

  View details for PubMedID 29719869

  View details for PubMedCentralID PMC5904434

• Chronic Kidney Disease Is Associated With Greater Bone Marrow Adiposity. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Woods, G. N., Ewing, S. K., Sigurdsson, S., Kado, D. M., Ix, J. H., Hue, T. F., Eiriksdottir, G., Xu, K., Gudnason, V., Lang, T. F., Vittinghoff, E., Harris, T. B., Rosen, C. J., Li, X., Schwartz, A. V. 2018; 33 (12): 2158-2164

  Abstract

  Bone marrow adiposity is associated with aging, osteoporosis, and reduced hematopoiesis, as well as anorexia nervosa, but little is known about the underlying mechanisms that affect marrow adiposity. Chronic kidney disease (CKD) may influence bone marrow adipose tissue (BMAT), possibly through loss of lean mass or higher circulating levels of sclerostin. To test these hypotheses, we investigated the cross-sectional association between estimated glomerular filtration rate (eGFR) as a measure of kidney function and 1 H-MRS-based measurement of vertebral BMAT (L1 to L4) in 475 older adults from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. Mean BMAT was compared in those with eGFR >60 (n = 297) versus those with eGFR 45 to 60 (n = 120) or eGFR <45 (n = 58) using linear regression models. Participants had a mean age of 81.5 (SD 4.1) years, mean eGFR of 64.3 (SD 16.1) mL/min/1.734 cm2 , mean BMAT of 54.5% (SD 8.5); 48.2% were women. In unadjusted and adjusted models (age, visit window, gender, diabetes and visceral adipose tissue), BMAT was higher in those with eGFR <45 (adjusted mean 58.5%; 95% CI, 56.2 to 60.7) compared with those with eGFR >60 (adjusted mean 53.8%; 95% CI, 52.8 to 54.8) (p = 0.0002). BMAT did not differ in those with eGFR 45 to 60 (adjusted mean 54.3%; 95% CI, 52.8 to 55.9) compared with those with eGFR >60 (p = 0.58). In a subgroup of participants with serum sclerostin available (n = 253), additional adjustment for sclerostin attenuated the difference in adjusted mean vertebral BMAT between those with eGFR <45 versus >60 from 3.7% (p = 0.04) to 2.4% (p = 0.20). CKD stage 3b or worse was associated with greater bone marrow adiposity; this association may be partially mediated by sclerostin. © 2018 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.3562

  View details for PubMedID 30075054

  View details for PubMedCentralID PMC6702945

• The relationships between physical performance, activity levels and falls in older men. The journals of gerontology. Series A, Biological sciences and medical sciences Orwoll, E. S., Fino, N. F., Gill, T. M., Cauley, J. A., Strotmeyer, E. S., Ensrud, K. E., Kado, D. M., Barrett-Connor, E., Bauer, D. C., Cawthon, P. M., Lapidus, J. 2018

  Abstract

  Physical performance and activity have both been linked to fall risk, but the way they are jointly associated with falls is unclear. We investigated how these two factors are related to incident falls in older men.In 2741 men (78.8±5 years) we evaluated the associations between activity and physical performance and how they jointly contributed to incident falls. Activity was assessed by accelerometry. Physical performance was measured by gait speed, dynamic balance (narrow walk), chair stand time, grip strength and leg power. Falls were ascertained by tri-annual questionnaires.Men were grouped into four categories based on activity and performance levels. The greatest number of falls (36-43%) and the highest fall rate (4.7-5.4/year among those who fell) (depending on the performance test) occurred in men with low activity/low performance, but most falls (57-64%) and relatively high fall rates (3.0-4.35/year) occurred in the other groups (low activity/high performance, high activity/high performance and high activity/low performance; 70% of men were in these groups). There were interactions between activity, performance (gait speed, narrow walk) and incident falls (p=0.001-0.02); predicted falls/yr. were highest in men with low activity/low performance, but there was also a peak of predicted falls in those with high activity.In community-dwelling older men, many falls occur in those with the lowest activity/worst physical performance but fall risk is also substantial with better activity and performance. Activity/physical performance assessments may improve identification of older men at risk of falls, and allow individualized approaches to prevention.

  View details for DOI 10.1093/gerona/gly248

  View details for PubMedID 30383210

• Metabolic Syndrome Does Not Modify the Association between Obesity and Hip Osteoarthritis Cheng, K., Ball, S., Schenk, S., Strotmeyer, E., Schousboe, J., Stefanick, M., Barrett-Connor, E., Kado, D., Nevitt, M., Lane, N. E., Orwoll, E., Hughes-Austin, J. M. WILEY. 2017

  View details for Web of Science ID 000411824105022

• Impact of Competing Risk of Mortality on Association of Weight Loss With Risk of Central Body Fractures in Older Men: A Prospective Cohort Study JOURNAL OF BONE AND MINERAL RESEARCH Ensrud, K. E., Harrison, S. L., Cauley, J. A., Langsetmo, L., Schousboe, J. T., Kado, D. M., Gourlay, M. L., Lyons, J. G., Fredman, L., Napoli, N., Crandall, C. J., Lewis, C. E., Orwoll, E. S., Stefanick, M. L., Cawthon, P. M. 2017; 32 (3): 624-632

  Abstract

  To determine the association of weight loss with risk of clinical fractures at the hip, spine, and pelvis (central body fractures [CBFs]) in older men with and without accounting for the competing risk of mortality, we used data from 4523 men (mean age 77.5 years). Weight change between baseline and follow-up (mean 4.5 years between examinations) was categorized as moderate loss (loss ≥10%), mild loss (loss 5% to <10%), stable (<5% change) or gain (gain ≥5%). Participants were contacted every 4 months after the follow-up examination to ascertain vital status (deaths verified by death certificates) and ask about fractures (confirmed by radiographic reports). Absolute probability of CBF by weight change category was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of CBF by weight change category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average of 8 years, 337 men (7.5%) experienced CBF and 1569 (34.7%) died before experiencing this outcome. Among men with moderate weight loss, CBF probability was 6.8% at 5 years and 16.9% at 10 years using Kaplan-Meier versus 5.7% at 5 years and 10.2% at 10 years using a competing risk approach. Men with moderate weight loss compared with those with stable weight had a 1.6-fold higher adjusted risk of CBF (HR 1.59; 95% CI, 1.06 to 2.38) using Cox models that was substantially attenuated in models accounting for competing mortality risk and no longer significant (subdistribution HR 1.16; 95% CI, 0.77 to 1.75). Results were similar in analyses substituting hip fracture for CBF. Older men with weight loss who survive are at increased risk of CBF, including hip fracture. However, ignoring the competing mortality risk among men with weight loss substantially overestimates their long-term fracture probability and relative fracture risk. © 2016 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.3020

  View details for Web of Science ID 000398055900022

• Bone Loss at the Hip and Subsequent Mortality in Older Men: The Osteoporotic Fractures in Men (MrOS) Study. JBMR plus Cawthon, P. M., Patel, S. n., Ewing, S. K., Lui, L. Y., Cauley, J. A., Lyons, J. G., Fredman, L. n., Kado, D. M., Hoffman, A. R., Lane, N. E., Ensrud, K. E., Cummings, S. R., Orwoll, E. S. 2017; 1 (1): 31–35

  Abstract

  Low bone mineral density (BMD) is associated with increased mortality risk, yet the impact of BMD loss on mortality is relatively unknown. We hypothesized that greater BMD loss is associated with increased mortality risk in older men. Change in femoral neck BMD was assessed in 4400 Osteoporotic Fractures in Men (MrOS) study participants with two to three repeat dual-energy X-ray absorptiometry scans over an average of 4.6 ± 0.4 (mean ± SD) years. Change in femoral neck BMD was estimated using mixed effects models; men were grouped into three categories of BMD change: maintenance (n = 1087; change ≥ 0 g/cm2); expected loss (n = 2768; change between 0 g/cm2 and <1 SD below mean change [>-0.034 g/cm2]); and accelerated loss (n = 545; change 1 SD below mean change or worse [≤-0.034 g/cm2]). Multivariate proportional hazards models adjusted for potential confounders estimated the risk of all-cause mortality over 8.1 ± 2.8 years following visit 2. Mortality was centrally adjudicated by physician review of death certificates. At visit 1, mean age was 72.9 ± 5.5 years. Men who maintained BMD were less likely to die during the subsequent follow-up period (33.7%) than men who had accelerated BMD loss (60.6%) (p < 0.001). Compared to men who had maintained BMD, those who had accelerated BMD loss had a 44% greater risk of mortality in multivariate-adjusted models (HR, 1.44; 95% CI, 1.23 to 1.68). Compared to men who had maintained BMD, there was no significant difference in mortality risk for men with expected loss of BMD (36.9% died) (multivariate HR, 1.00; 95% CI, 0.89 to 1.13). Further adjustment for visit 1 or visit 2 BMD measurement did not substantially alter these associations. Results for total hip BMD were similar. In conclusion, accelerated loss of BMD at the hip is a risk factor for mortality in men that is not explained by comorbidity burden, concurrent change in weight, or physical activity.

  View details for PubMedID 29124252

• Cross-Sectional and Longitudinal Associations of Diffuse Idiopathic Skeletal Hyperostosis and Thoracic Kyphosis in Older Men and Women. Arthritis care & research Katzman, W. B., Parimi, N., Mansoori, Z., Nardo, L., Kado, D. M., Cawthon, P. M., Marshall, L. M., Schousboe, J. T., Lane, N. E. 2017; 69 (8): 1245-1252

  Abstract

  To investigate cross-sectional and longitudinal associations of diffuse idiopathic skeletal hyperostosis (DISH) and thoracic kyphosis in older persons.DISH and kyphosis were assessed in 1,500 men from the Osteoporotic Fractures in Men (MrOS) study and in 1,267 women from the Study of Osteoporotic Fractures (SOF). DISH was assessed using baseline lateral spine radiographs, and Cobb angle of kyphosis was measured from baseline and followup radiographs, a mean 4.6 years later in men, and 3.7 and 15 years later in women. Linear regression was used to analyze associations of DISH with baseline Cobb angle and with percent annualized change in Cobb angle. We tested for heterogeneity among studies.DISH was identified in 222 participants in MrOS (15%) and in 156 participants in SOF (12%). Participants with DISH in both cohorts had higher baseline Cobb angles (P < 0.05), after adjustment for covariates. After approximately 4 years of followup, there was no significant difference in annualized percent change in Cobb angle in those with DISH compared to those without DISH (P > 0.05) for men or women. Women with DISH had less kyphosis progression over 15 years (0.25% less annualized change in Cobb) than those without DISH.Prevalent DISH is associated with greater kyphosis in older men and women, and is not significantly associated with a change in kyphosis over 4-5 years. However, in women followed over 15 years, DISH was associated with less progression of kyphosis. These results suggest that DISH influences kyphosis and may slow progression over the long term. Additional studies of DISH/kyphosis associations are warranted to understand the functional implications of this finding.

  View details for DOI 10.1002/acr.23115

  View details for PubMedID 27723250

  View details for PubMedCentralID PMC5385297

• A Prospective Study of Back Pain and Risk of Falls Among Older Community-dwelling Men. The journals of gerontology. Series A, Biological sciences and medical sciences Marshall, L. M., Litwack-Harrison, S., Makris, U. E., Kado, D. M., Cawthon, P. M., Deyo, R. A., Carlson, N. L., Nevitt, M. C. 2017; 72 (9): 1264-1269

  Abstract

  Musculoskeletal pain is associated with increased fall risk among older men. However, the association of back pain, the most prevalent type of pain in this population, and fall risk is unknown.We conducted a prospective investigation among 5,568 community-dwelling U.S. men at least 65 years of age from the Osteoporotic Fractures in Men Study (MrOS). Baseline questionnaires inquired about back pain and its location (such as low back), severity, and frequency in the past year. During 1 year of follow-up, falls were summed from self-reports obtained every 4 months. Outcomes were recurrent falls (≥2 falls) and any fall (≥1 fall). Associations of back pain and fall risk were estimated with risk ratios (RRs) and 95% confidence intervals (CIs) from multivariable log-binomial regression models adjusted for age, dizziness, arthritis, knee pain, urinary symptoms, self-rated health, central nervous system medication use, and instrumental activities of daily living.Most (67%) reported any back pain in the past year. During follow-up, 11% had recurrent falls and 25% fell at least once. Compared with no back pain, any back pain was associated with elevated recurrent fall risk (multivariable RR = 1.3, 95% CI: 1.1, 1.5). Multivariable RRs for 1, 2, and 3+ back pain locations were, respectively, 1.2 (95% CI: 1.0, 1.5), 1.4 (1.1, 1.8), and 1.7 (95% CI: 1.3, 2.2). RRs were also elevated for back pain severity and frequency. Back pain was also associated with risk of any fall.Among older men, back pain is independently associated with increased fall risk.

  View details for DOI 10.1093/gerona/glw227

  View details for PubMedID 27852636

  View details for PubMedCentralID PMC5861977

• Trunk lean mass and its association with 4 different measures of thoracic kyphosis in older community dwelling persons. PloS one Yamamoto, J., Bergstrom, J., Davis, A., Wing, D., Schousboe, J. T., Nichols, J. F., Kado, D. M. 2017; 12 (4): e0174710

  Abstract

  The causes of age-related hyperkyphosis (HK) include osteoporosis, but only 1/3 of those most severely affected have vertebral fractures, suggesting that there are other important, and potentially modifiable causes. We hypothesized that muscle mass and quality may be important determinants of kyphosis in older persons.We recruited 72 persons >65 years to participate in a prospective study designed to evaluate kyphosis and fall risk. At the baseline visit, participants had their body composition measures completed using Dual Energy X-ray Absorptiometry (DXA). They had kyphosis measured in either the standing [S] or lying [L] position: 1) Cobb angle from DXA [L]; 2) Debrunner kyphometer [S]; 3) architect's flexicurve ruler [S]; and 4) blocks method [L]. Multivariable linear/logistic regression analyses were done to assess the association between each body composition and 4 kyphosis measures.Women (n = 52) were an average age of 76.8 (SD 6.7) and men 80.5 (SD 7.8) years. They reported overall good/excellent health (93%), the average body mass index was 25.3 (SD 4.6) and 35% reported a fall in the past year. Using published cut-offs, about 20-30% were determined to have HK. For the standing assessments of kyphosis only, after adjusting for age, sex, weight and hip BMD, persons with lower TLM were more likely to be hyperkyphotic.Lower TLM is associated with HK in older persons. The results were stronger when standing measures of kyphosis were used, suggesting that the effects of muscle on thoracic kyphosis are best appreciated under spinal loading conditions.

  View details for DOI 10.1371/journal.pone.0174710

  View details for PubMedID 28369088

  View details for PubMedCentralID PMC5378351

• Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Impaired Physical Function: The Rancho Bernardo Study. Journal of the American Geriatrics Society Katzman, W. B., Huang, M. H., Kritz-Silverstein, D., Barrett-Connor, E., Kado, D. M. 2017; 65 (7): 1476-1481

  Abstract

  Investigate associations of diffuse idiopathic skeletal hyperostosis (DISH) with self-reported and measured physical function in older adults.Cross-sectional analyses of data collected in 1992-96 from a longitudinal cohort.Research clinic within a community.Community-dwelling men (n = 630) and women (n = 961), mean age 71.5 years (SD = 10.8), from the Rancho Bernardo Study.DISH assessed from lateral thoracic and lumbar spine radiographs; self-reported difficulty bending over to the floor, walking 2-3 level blocks, or climbing 1 flight of stairs; performance-based measures of grip strength and chair-stand testing (ability to stand up and sit down in a chair 5 times without using chair arms).DISH was present in 25.6% of men and 5.5% of women. In age and sex-adjusted models, those with DISH had 1.72-fold increased odds (95% CI: 1.13, 2.62) of self-reported difficulty bending; this remained significant after further adjustment for Cobb angle, weight, stroke, arthritis, and exercise, OR = 1.69, (95% CI: 1.07, 2.66). In fully adjusted multivariate models, those with DISH had worse grip strength, -1.08 kg, P = .01, but did not differ from those without DISH on walking or climbing stairs. In sex-stratified, fully adjusted models, among men only, those with DISH were 2.17-times (95% CI: 1.04, 4.52) more likely to be unable to complete 5 chair stands without using their arms.DISH was less prevalent in women but affected almost one-quarter of older white men. People with DISH are more likely to experience physical functional impairment, suggesting that DISH has clinical correlations and is not an incidental radiographic finding.

  View details for DOI 10.1111/jgs.14810

  View details for PubMedID 28369706

  View details for PubMedCentralID PMC5507717

• Targeted spine strengthening exercise and posture training program to reduce hyperkyphosis in older adults: results from the study of hyperkyphosis, exercise, and function (SHEAF) randomized controlled trial. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA Katzman, W. B., Vittinghoff, E., Lin, F., Schafer, A., Long, R. K., Wong, S., Gladin, A., Fan, B., Allaire, B., Kado, D. M., Lane, N. E. 2017; 28 (10): 2831-2841

  Abstract

  A 6-month randomized controlled trial of spine-strengthening exercise and posture training reduced both radiographic and clinical measures of kyphosis. Participants receiving the intervention improved self-image and satisfaction with their appearance. Results suggest that spine-strengthening exercise and postural training may be an effective treatment option for older adults with hyperkyphosis.The purpose of the present study is to determine in a randomized controlled trial whether spine-strengthening exercises improve Cobb angle of kyphosis in community-dwelling older adults.We recruited adults ≥60 years with kyphosis ≥40° and enrolled 99 participants (71 women, 28 men), mean age 70.6 ± 0.6 years, range 60-88, with baseline Cobb angle 57.4 ± 12.5°. The intervention included group spine-strengthening exercise and postural training, delivered by a physical therapist, 1-h, three times weekly for 6 months. Controls received four group health education meetings. The primary outcome was change in the gold standard Cobb angle of kyphosis measured from standing lateral spine radiographs. Secondary outcomes included change in kyphometer-measured kyphosis, physical function (modified Physical Performance Test, gait speed, Timed Up and Go, Timed Loaded Standing, 6-Min Walk), and health-related quality of life (HRQoL) (PROMIS global health and physical function indexes, SRS-30 self-image domain). ANCOVA was used to assess treatment effects on change from baseline to 6 months in all outcomes.There was a -3.0° (95% CI -5.2, -0.8) between-group difference in change in Cobb angle, p = 0.009, favoring the intervention and approximating the magnitude of change from an incident vertebral fracture. Kyphometer-measured kyphosis (p = 0.03) and SRS-30 self-esteem (p < 0.001) showed favorable between-group differences in change, with no group differences in physical function or additional HRQoL outcomes, p > 0.05.Spine-strengthening exercise and posture training over 6 months reduced kyphosis compared to control. Our randomized controlled trial results suggest that a targeted kyphosis-specific exercise program may be an effective treatment option for older adults with hyperkyphosis.ClinicalTrials.gov; identifier NCT01751685.

  View details for DOI 10.1007/s00198-017-4109-x

  View details for PubMedID 28689306

  View details for PubMedCentralID PMC5873977

• Association of Incident, Clinically Undiagnosed Radiographic Vertebral Fractures With Follow-Up Back Pain Symptoms in Older Men: the Osteoporotic Fractures in Men (MrOS) Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Fink, H. A., Litwack-Harrison, S., Ensrud, K. E., Shen, J., Schousboe, J. T., Cawthon, P. M., Cauley, J. A., Lane, N. E., Taylor, B. C., Barrett-Connor, E., Kado, D. M., Cummings, S. R., Marshall, L. M. 2017; 32 (11): 2263-2268

  Abstract

  Prior data in women suggest that incident clinically undiagnosed radiographic vertebral fractures (VFs) often are symptomatic, but misclassification of incident clinical VF may have biased these estimates. There are no comparable data in men. To evaluate the association of incident clinically undiagnosed radiographic VF with back pain symptoms and associated activity limitations, we used data from the Osteoporotic Fractures in Men (MrOS) Study, a prospective cohort study of community-dwelling men aged ≥65 years. A total of 4396 men completed spine X-rays and symptom questionnaires at baseline and visit 2, about 4.6 years later. Incident clinical VFs during this interval were defined by self-reported clinical diagnosis plus community imaging showing a centrally adjudicated ≥1 increase in semiquantitative (SQ) grade in any thoracic or lumbar vertebra versus baseline study X-rays. Incident radiographic VFs (≥1 increase in SQ grade between baseline and visit 2 study X-rays) were categorized as radiographic-only (not clinically diagnosed) or radiographic plus clinical (also clinically diagnosed). Multivariable-adjusted log binomial regression was used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs). Men with incident radiographic plus clinical VF were most likely to have back pain symptoms and associated activity limitation at follow-up. However, versus men without incident VF, those with incident radiographic-only VF also were significantly more likely at follow-up to report any back pain (70% versus 59%; PR, 1.2 [95% CI, 1.1 to 1.3]), severe back pain (8% versus 4%; PR, 1.9 [95% CI, 1.1 to 3.3]), bother from back pain most/all the time (22% versus 13%; PR, 1.7 [95% CI, 1.3 to 2.2]), and limited usual activity from back pain (34% versus 18%; PR, 1.9 [95% CI, 1.5 to 2.4]). Clinically undiagnosed, incident radiographic VFs were associated with an increased likelihood of back pain symptoms and associated activity limitation. Results suggest incident radiographic-only VFs often were symptomatic, and were associated with both new and worsening back pain. Preventing these fractures may reduce back pain and related disability in older men. © 2017 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.3215

  View details for PubMedID 28880398

  View details for PubMedCentralID PMC5685921

• Comparison of fracture risk assessment tools in older men without prior hip or spine fracture: the MrOS study. Archives of osteoporosis Gourlay, M. L., Ritter, V. S., Fine, J. P., Overman, R. A., Schousboe, J. T., Cawthon, P. M., Orwoll, E. S., Nguyen, T. V., Lane, N. E., Cummings, S. R., Kado, D. M., Lapidus, J. A., Diem, S. J., Ensrud, K. E. 2017; 12 (1): 91

  Abstract

  Femoral neck bone mineral density (BMD), age plus femoral neck BMD T score, and three externally generated fracture risk tools had similar accuracy to identify older men who developed osteoporotic fractures. Risk tools with femoral neck BMD performed better than those without BMD. The externally developed risk tools were poorly calibrated.We compared the performance of fracture risk assessment tools in older men, accounting for competing risks including mortality.A comparative ROC curve analysis assessed the ability of the QFracture, FRAX® and Garvan fracture risk tools, and femoral neck bone mineral density (BMD) T score with or without age to identify incident fracture in community-dwelling men aged 65 years or older (N = 4994) without hip or clinical vertebral fracture or antifracture treatment at baseline.Among risk tools calculated with BMD, the discriminative ability to identify men with incident hip fracture was similar for FRAX (AUC 0.77, 95% CI 0.73, 0.81), the Garvan tool (AUC 0.78, 95% CI 0.74, 0.82), age plus femoral neck BMD T score (AUC 0.79, 95% CI 0.75, 0.83), and femoral neck BMD T score alone (AUC 0.76, 95% CI 0.72, 0.81). Among risk tools calculated without BMD, the discriminative ability to identify hip fracture was similar for QFracture (AUC 0.69, 95% CI 0.66, 0.73), FRAX (AUC 0.70, 95% CI 0.66, 0.73), and the Garvan tool (AUC 0.71, 95% CI 0.67, 0.74). Correlated ROC curve analyses revealed better diagnostic accuracy for risk scores calculated with BMD compared with QFracture (P < 0.0001). Calibration was good for the internally generated BMD T score predictor with or without age and poor for the externally developed risk tools.In untreated older men without fragility fractures at baseline, an age plus femoral neck BMD T score classifier identified men with incident hip fracture as accurately as more complicated fracture risk scores.

  View details for DOI 10.1007/s11657-017-0389-1

  View details for PubMedID 29052793

  View details for PubMedCentralID PMC5695884

• Effect of Combination Folic Acid, Vitamin B6 , and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Stone, K. L., Lui, L. Y., Christen, W. G., Troen, A. M., Bauer, D. C., Kado, D., Schambach, C., Cummings, S. R., Manson, J. E. 2017; 32 (12): 2331-2338

  Abstract

  Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12 , B6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard = 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. © 2017 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.3229

  View details for PubMedID 29244251

  View details for PubMedCentralID PMC5734110

• Impact of Competing Risk of Mortality on Association of Weight Loss with Risk of Central Body Fractures in Older Men: A Prospective Cohort Study. Journal of bone and mineral research Ensrud, K. E., Harrison, S. L., Cauley, J. A., Langsetmo, L., Schousboe, J. T., Kado, D. M., Gourlay, M. L., Lyons, J. G., Fredman, L., Napoli, N., Crandall, C. J., Lewis, C. E., Orwoll, E. S., Stefanick, M. L., Cawthon, P. M. 2016

  Abstract

  To determine the association of weight loss with risk of clinical fractures at the hip, spine, and pelvis (central body fractures [CBFs]) in older men with and without accounting for the competing risk of mortality, we used data from 4523 men (mean age 77.5 years). Weight change between baseline and follow-up (mean 4.5 years between examinations) was categorized as moderate loss (loss ≥10%), mild loss (loss 5% to <10%), stable (<5% change) or gain (gain ≥5%). Participants were contacted every 4 months after the follow-up examination to ascertain vital status (deaths verified by death certificates) and ask about fractures (confirmed by radiographic reports). Absolute probability of CBF by weight change category was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of CBF by weight change category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average of 8 years, 337 men (7.5%) experienced CBF and 1569 (34.7%) died before experiencing this outcome. Among men with moderate weight loss, CBF probability was 6.8% at 5 years and 16.9% at 10 years using Kaplan-Meier versus 5.7% at 5 years and 10.2% at 10 years using a competing risk approach. Men with moderate weight loss compared with those with stable weight had a 1.6-fold higher adjusted risk of CBF (HR 1.59; 95% CI, 1.06 to 2.38) using Cox models that was substantially attenuated in models accounting for competing mortality risk and no longer significant (subdistribution HR 1.16; 95% CI, 0.77 to 1.75). Results were similar in analyses substituting hip fracture for CBF. Older men with weight loss who survive are at increased risk of CBF, including hip fracture. However, ignoring the competing mortality risk among men with weight loss substantially overestimates their long-term fracture probability and relative fracture risk. © 2016 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.3020

  View details for PubMedID 27739103

• Risk Factors for Hip Fracture in Older Men: The Osteoporotic Fractures in Men Study (MrOS). Journal of bone and mineral research Cauley, J. A., Cawthon, P. M., Peters, K. E., Cummings, S. R., Ensrud, K. E., Bauer, D. C., Taylor, B. C., Shikany, J. M., Hoffman, A. R., Lane, N. E., Kado, D. M., Stefanick, M. L., Orwoll, E. S. 2016; 31 (10): 1810-1819

  Abstract

  Almost 30% of hip fractures occur in men; the mortality, morbidity, and loss of independence after hip fractures are greater in men than in women. To comprehensively evaluate risk factors for hip fracture in older men, we performed a prospective study of 5994 men, primarily white, age 65+ years recruited at six US clinical centers. During a mean of 8.6 years of 97% complete follow-up, 178 men experienced incident hip fractures. Information on risk factors including femoral neck bone mineral density (FNBMD) was obtained at the baseline visit. Cox proportional hazards models were used to calculate the hazard ratio (HR) with 95% confidence intervals; Fine and Gray models adjusted for competing mortality risk. Older age (≥75 years), low FNBMD, currently smoking, greater height and height loss since age 25 years, history of fracture, use of tricyclic antidepressants, history of myocardial infarction or angina, hyperthyroidism or Parkinson's disease, lower protein intake, and lower executive function were all associated with an increased hip fracture risk. Further adjustment for competing mortality attenuated HR for smoking, hyperthyroidism, and Parkinson's disease. The incidence rate of hip fracture per 1000 person-years (PY) was greatest in men with FNBMD T-scores <-2.5 (white women reference database) who also had 4+ risk factors, 33.4. Men age ≥80 years with 3+ major comorbidities experienced hip fracture at rates of 14.52 versus 0.88 per 1000 PY in men age <70 years with zero comorbidities. Older men with low FNBMD, multiple risk factors, and multimorbidity have a high risk of hip fracture. Many of these assessments can easily be incorporated into routine clinical practice and may lead to improved risk stratification. © 2016 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.2836

  View details for PubMedID 26988112

• Sex hormones, sex hormone binding globulin, and vertebral fractures in older men BONE Cawthon, P. M., Schousboe, J. T., Harrison, S. L., Ensrud, K. E., Black, D., Cauley, J. A., Cummings, S. R., LeBlanc, E. S., Laughlin, G. A., Nielson, C. M., Broughton, A., Kado, D. M., Hoffman, A. R., Jamal, S. A., Barrett-Connor, E., Orwoll, E. S. 2016; 84: 271-278

  Abstract

  The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.

  View details for DOI 10.1016/j.bone.2016.01.009

  View details for PubMedID 26778261

• The association between bone turnover markers and kyphosis in community-dwelling older adults. Bone reports McDaniels-Davidson, C. R., Kritz-Silverstein, D., Huang, M. H., Laughlin, G. A., Johnson, S., Haapalahti, J., Schneider, D. L., Barrett-Connor, E., Kado, D. M. 2016; 5: 57-61

  Abstract

  Hyperkyphosis, accentuated curvature of the thoracic spine, is often attributed to osteoporosis, yet its underlying pathophysiology is not well understood. Bone turnover markers (BTM) reflect the dynamic process of bone formation and resorption. This study examined the association between serum BTM levels and kyphosis in community-dwelling older adults.Between 2003 and 2006, 760 men and women in the Rancho Bernardo Study age 60 and older had blood drawn and kyphosis measured. Fasting serum was assayed for N-telopeptide (NTX) and procollagen type 1 n-terminal propeptide (P1NP), markers of bone resorption and formation, respectively. Participants requiring two or more 1.7 cm blocks under their head to achieve a neutral supine position were classified as having accentuated kyphosis. Analyses were stratified by sex and use of estrogen therapy (ET). Odds of accentuated kyphosis were calculated for each standard deviation increase in log-transformed BTM.Mean age was 75 years. Overall, 51% of 341 non-ET using women, 41% of 111 ET-using women, and 75% of 308 men had accentuated kyphosis. In adjusted models, higher P1NP and NTX were associated with decreased odds of accentuated kyphosis in non-ET using women (P1NP: OR = 0.78 [95% CI, 0.58-0.92]; NTX: OR = 0.68 [95% CI, 0.54-0.86]), but not in men or ET-using women (p > 0.05).The selective association of higher bone turnover with reduced odds of accentuated kyphosis in non-ET using women suggests that elevated BTM were associated with a lower likelihood of hyperkyphosis only in the low estrogen/high BTM environment characteristic of postmenopausal women who are not using ET.

  View details for DOI 10.1016/j.bonr.2016.04.001

  View details for PubMedID 27868084

  View details for PubMedCentralID PMC4926834

• Degree of Trauma Differs for Major Osteoporotic Fracture Events in Older Men Versus Older Women. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Ensrud, K. E., Blackwell, T. L., Cawthon, P. M., Bauer, D. C., Fink, H. A., Schousboe, J. T., Black, D. M., Orwoll, E. S., Kado, D. M., Cauley, J. A., Mackey, D. C. 2016; 31 (1): 204-7

  Abstract

  To examine the degree of trauma in major osteoporotic fractures (MOF) in men versus women, we used data from 15,698 adults aged ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study (5994 men) and the Study of Osteoporotic Fractures (SOF) (9704 women). Participants were contacted tri-annually to ascertain incident fractures, which were confirmed by radiographic reports and coded according to degree of self-reported trauma. Trauma was classified as low (fall from ≤ standing height; fall on stairs, steps, or curb; minimal trauma other than fall [coughing, turning over]); moderate (collisions with objects during normal activity without associated fall); or high (fall from > standing height; severe trauma [motor vehicle accident, assault]). MOF included hip, clinical vertebral, wrist, and humerus fractures. Mean fracture follow-up was 9.1 years in SOF and 8.7 years in MrOS. A total of 14.6% of the MOF in men versus 6.3% of the MOF in women were classified as high trauma (p < 0.001); men versus women more often experienced fractures resulting from severe trauma as well as from fall > standing height. High-trauma fractures were more significantly common in men versus women at the hip (p = 0.002) and wrist (p < 0.001) but not at the spine or humerus. Among participants with MOF, the odds ratio of a fracture related to high-trauma fracture among men versus women was 3.12 (95% confidence interval [CI] 1.70-5.71) after adjustment for traditional risk factors. Findings were similar in analyses limited to participants with hip fractures (odds ratio [OR] = 3.34, 95% CI 1.04-10.67) and those with wrist fracture (OR = 5.68, 95% CI 2.03-15.85). Among community-dwelling older adults, MOF are more likely to be related to high trauma in men than in women. These findings are not explained by sex differences in conventional risk factors and may reflect a greater propensity among men to engage in risky behavior. © 2015 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.2589

  View details for PubMedID 26178795

  View details for PubMedCentralID PMC4730881

• Study of Hyperkyphosis, Exercise and Function (SHEAF) Protocol of a Randomized Controlled Trial of Multimodal Spine-Strengthening Exercise in Older Adults With Hyperkyphosis. Physical therapy Katzman, W. B., Vittinghoff, E., Kado, D. M., Schafer, A. L., Wong, S. S., Gladin, A., Lane, N. E. 2016; 96 (3): 371-81

  Abstract

  Hyperkyphosis negatively affects health status, physical mobility, and quality of life, but there is no standard protocol for treating people with hyperkyphosis. Treatment options include targeted exercise.This single-site randomized controlled trial (RCT) will determine the efficacy of a targeted multimodal spine-strengthening exercise program, compared with no exercise intervention, among community-dwelling men and women aged ≥60 years.The RCT is a parallel-group design, with 1:1 randomization to exercise and attentional control groups.The study will be conducted at one primary site (one academic medical center partnered with one local community medical center).One hundred men and women, aged ≥60 years, with thoracic kyphosis ≥40 degrees will be randomized.The targeted multimodal spine-strengthening exercise intervention includes exercise and postural training delivered by a physical therapist in a group of 10 participants, 3 times a week for 6 months. Controls receive monthly health education meetings in a group of 10 participants and monthly calls from the study coordinator to monitor physical activity and any adverse events.The primary outcome is change in Cobb angle of kyphosis measured from lateral spine radiographs at baseline and 6 months. Secondary outcomes include change in physical function (assessed with the modified Physical Performance Test, Timed "Up & Go" Test, timed loaded standing, 4-m walk, and Six-Minute Walk Test) and health-related quality of life (assessed with the modified Scoliosis Research Society instrument [SRS-30] self-image domain and Patient Reported Outcomes Measurement Information System [PROMIS] global health and physical function indexes). Additional secondary outcomes include pain, physical activity level, spinal flexion and extension muscle strength, paraspinal extensor muscle density, and adverse events.Blinding of the participants and instructors providing the intervention is not possible.The efficacy of a high-quality, adequately powered exercise intervention in men and women with kyphosis ≥40 degrees will be evaluated to determine whether targeted multimodal spine-strengthening exercise reduces hyperkyphosis in older adults and improves important secondary outcomes of physical function and health-related quality of life.

  View details for DOI 10.2522/ptj.20150171

  View details for PubMedID 26251480

  View details for PubMedCentralID PMC4774389

• Clinical utility of routine laboratory testing to identify possible secondary causes in older men with osteoporosis: the Osteoporotic Fractures in Men (MrOS) Study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA Fink, H. A., Litwack-Harrison, S., Taylor, B. C., Bauer, D. C., Orwoll, E. S., Lee, C. G., Barrett-Connor, E., Schousboe, J. T., Kado, D. M., Garimella, P. S., Ensrud, K. E. 2016; 27 (1): 331-8

  Abstract

  We investigated the value of routine laboratory testing for identifying underlying causes in older men diagnosed with osteoporosis. Most osteoporotic and nonosteoporotic men had ≥1 laboratory abnormality. Few individual laboratory abnormalities were more common in osteoporotic men. The benefit of routine laboratory testing in older osteoporotic men may be low.To evaluate the utility of recommended laboratory testing to identify secondary causes in older men with osteoporosis, we examined prevalence of laboratory abnormalities in older men with and without osteoporosis.One thousand five hundred seventy-two men aged ≥65 years in the Osteoporotic Fractures in Men study completed bone mineral density (BMD) testing and a battery of laboratory measures, including serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), 25-OH vitamin D, total testosterone, spot urine calcium/creatinine ratio, spot urine albumin/creatinine ratio, creatinine-derived estimated glomerular filtration rate, 24-h urine calcium, and 24-h urine free cortisol. Using cross-sectional analyses, we calculated prevalence ratios (PRs) and 95 % confidence intervals (CI) for the association of any and specific laboratory abnormalities with osteoporosis and the number of men with osteoporosis needed to test to identify one additional laboratory abnormality compared to testing men without osteoporosis.Approximately 60 % of men had ≥1 laboratory abnormality in both men with and without osteoporosis. Among individual tests, only vitamin D insufficiency (PR, 1.13; 95 % CI, 1.05-1.22) and high alkaline phosphatase (PR, 3.05; 95 % CI, 1.52-6.11) were more likely in men with osteoporosis. Hypercortisolism and hyperthyroidism were uncommon and not significantly more frequent in men with osteoporosis. No osteoporotic men had hypercalciuria.Though most of these older men had ≥1 laboratory abnormality, few routinely recommended individual tests were more common in men with osteoporosis than in those without osteoporosis. Possibly excepting vitamin D and alkaline phosphatase, benefit of routine laboratory testing to identify possible secondary causes in older osteoporotic men appears low. Results may not be generalizable to younger men or to older men in whom history and exam findings raise clinical suspicion for a secondary cause of osteoporosis.

  View details for DOI 10.1007/s00198-015-3356-y

  View details for PubMedID 26458388

  View details for PubMedCentralID PMC4719570

• Correlations among four measures of thoracic kyphosis in older adults. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA Tran, T. H., Wing, D., Davis, A., Bergstrom, J., Schousboe, J. T., Nichols, J. F., Kado, D. M. 2016; 27 (3): 1255-1259

  Abstract

  There are many ways to measure thoracic kyphosis ranging from simple clinical to more complex assessments. We evaluated the correlation among four commonly used kyphosis measures: Cobb angle, Debrunner kyphometer, kyphotic index, and the blocks method. Each measure was correlated with the others, confirming high clinical and research applicability.The purpose of this study was to assess the associations among four commonly used measures of thoracic kyphosis in older adults.Seventy two men and women aged 65-96 were recruited from the San Diego community. Four kyphosis measures were assessed in the same person during a baseline clinic visit. Two measures were done in the lying (L) and two in the standing (ST) position: (1) Cobb angle calculated from dual X-Ray absorptiometry (DXA) images (L), (2) Debrunner kyphometer (DK) angle measured by a protractor (ST), (3) kyphotic index (KI) calculated using an architect's flexicurve ruler (ST), and (4) the blocks method involving counting the number of 1.7 cm-thick blocks required to achieve a neutral head position while lying flat on the DXA table (L). Spearman rank correlation coefficients were used to determine the strength of the association between each kyphosis measure.Using the Cobb angle as the gold standard, the blocks method demonstrated the lowest correlation (r(s) = 0.63, p < 0.0001), the Debrunner method had a moderate correlation (r(s) = 0.65, p < 0.0001), and the kyphotic index had the highest correlation (r(s) = 0.68, p < 0.0001). The correlation was strongest between the kyphotic index and the Debrunner kyphometer (r(s) = 0.76, p < 0.0001).In older men and women, all four measures of thoracic kyphosis were significantly correlated with each other, whether assessed in the lying or standing position. Thus, any of these measures demonstrate both potential clinical and research utility.

  View details for DOI 10.1007/s00198-015-3368-7

  View details for PubMedID 26475287

  View details for PubMedCentralID PMC5332161

• A Prospective Study of Back Pain and Risk of Falls Among Older Community-dwelling Women. The journals of gerontology. Series A, Biological sciences and medical sciences Marshall, L. M., Litwack-Harrison, S., Cawthon, P. M., Kado, D. M., Deyo, R. A., Makris, U. E., Carlson, H. L., Nevitt, M. C. 2016; 71 (9): 1177-83

  Abstract

  Back pain and falls are common health conditions among older U.S. women. The extent to which back pain is an independent risk factor for falls has not been established.We conducted a prospective study among 6,841 community-dwelling U.S. women at least 65 years of age from the Study of Osteoporotic Fractures (SOF). Baseline questionnaires inquired about any back pain, pain severity, and frequency in the past year. During 1 year of follow-up, falls were summed from self-reports obtained every 4 months. Two outcomes were studied: recurrent falls (≥2 falls) and any fall (≥1 fall). Associations of back pain and each fall outcome were estimated with risk ratios (RRs) and 95% confidence intervals (CIs) from multivariable log-binomial regression. Adjustments were made for age, education, smoking status, fainting history, hip pain, stroke history, vertebral fracture, and Geriatric Depression Scale.Most (61%) women reported any back pain. During follow-up, 10% had recurrent falls and 26% fell at least once. Any back pain relative to no back pain was associated with a 50% increased risk of recurrent falls (multivariable RR = 1.5, 95% CI: 1.3, 1.8). Multivariable RRs for recurrent falls were significantly elevated for all back pain symptoms, ranging from 1.4 (95% CI: 1.1, 1.8) for mild back pain to 1.8 (95% CI: 1.4, 2.3) for activity-limiting back pain. RRs of any fall were also significantly increased albeit smaller than those for recurrent falls.Older community-dwelling women with a recent history of back pain are at increased risk for falls.

  View details for DOI 10.1093/gerona/glv225

  View details for PubMedID 26757988

  View details for PubMedCentralID PMC4978357

• Thoracic kyphosis and rate of incident vertebral fractures: the Fracture Intervention Trial. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA Katzman, W. B., Vittinghoff, E., Kado, D. M., Lane, N. E., Ensrud, K. E., Shipp, K. 2016; 27 (3): 899-903

  Abstract

  Biomechanical analyses support the theory that thoracic spine hyperkyphosis may increase risk of new vertebral fractures. While greater kyphosis was associated with an increased rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture.Biomechanical analyses suggest hyperkyphosis may increase risk of incident vertebral fracture by increasing the load on vertebral bodies during daily activities. We propose to assess the association of kyphosis with incident radiographic vertebral fracture.We used data from the Fracture Intervention Trial among 3038 women 55-81 years of age with low bone mineral density (BMD). Baseline kyphosis angle was measured using a Debrunner kyphometer. Vertebral fractures were assessed at baseline and follow-up from lateral radiographs of the thoracic and lumbar spine. We used Poisson models to estimate the independent association of kyphosis with incident fracture, controlling for age and femoral neck BMD.Mean baseline kyphosis was 48° (SD = 12) (range 7-83). At baseline, 962 (32%) participants had a prevalent fracture. There were 221 incident fractures over a median of 4 years. At baseline, prevalent fracture was associated with 3.7° greater average kyphosis (95% CI 2.8-4.6, p < 0.0005), adjusting for age and femoral neck BMD. Before adjusting for prevalent fracture, each 10° greater kyphosis was associated with 22% increase (95% CI 8-38%, p = 0.001) in annualized rate of new radiographic vertebral fracture, adjusting for age and femoral neck BMD. After additional adjustment for prevalent fracture, estimated increased annualized rate was attenuated and no longer significant, 8% per 10° kyphosis (95% CI -4 to 22%, p = 0.18).While greater kyphosis increased the rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture.

  View details for DOI 10.1007/s00198-015-3478-2

  View details for PubMedID 26782685

  View details for PubMedCentralID PMC4939887

• Time to Osteoporosis and Major Fracture in Older Men: The MrOS Study. American journal of preventive medicine Gourlay, M. L., Overman, R. A., Fine, J. P., Filteau, G., Cawthon, P. M., Schousboe, J. T., Orwoll, E. S., Wilt, T. J., Nguyen, T. V., Lane, N. E., Szulc, P., Taylor, B. C., Dam, T. T., Nielson, C. M., Cauley, J. A., Barrett-Connor, E., Fink, H. A., Lapidus, J. A., Kado, D. M., Diem, S. J., Ensrud, K. E. 2016; 50 (6): 727-736

  Abstract

  For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals.A prospective cohort study of 5,415 community-dwelling men aged ≥65 years without hip or clinical vertebral fracture or antifracture treatment at baseline was conducted. Participants had concurrent BMD and fracture follow-up between 2000 and 2009, and additional fracture follow-up through 2014. Data were analyzed in 2015. Time to incident osteoporosis (lowest T-score ≤ -2.50) for men without baseline osteoporosis, and time to hip or clinical vertebral fracture or major osteoporotic fracture for men without or with baseline osteoporosis, were estimated.Nine men (0.2%) with BMD T-scores >-1.50 at baseline developed osteoporosis during follow-up. The adjusted estimated time for 10% to develop osteoporosis was 8.5 (95% CI=6.7, 10.9) years for those with moderate osteopenia (lowest T-score, -1.50 to -1.99) and 2.7 (95% CI=2.1, 3.4) years for those with advanced osteopenia (lowest T-score, -2.00 to -2.49) at baseline. The adjusted times for 3% to develop a first hip or clinical vertebral fracture ranged from 7.1 (95% CI=6.0, 8.3) years in men with baseline T-scores > -1.50 to 1.7 (95% CI=1.0, 3.1) years in men with baseline osteoporosis.Men aged 65 years and older with femoral neck, total hip, and lumbar spine BMD T-scores >-1.50 on a first BMD test were very unlikely to develop osteoporosis during follow-up. Additional BMD testing may be most informative in older men with T-scores ≤-1.50.

  View details for DOI 10.1016/j.amepre.2015.11.015

  View details for PubMedID 26821835

  View details for PubMedCentralID PMC4875888

• What Proportion of Incident Radiographic Vertebral Fractures in Older Men Is Clinically Diagnosed and Vice Versa: A Prospective Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Ensrud, K. E., Blackwell, T. L., Fink, H. A., Zhang, J., Cauley, J. A., Cawthon, P. M., Black, D. M., Bauer, D. C., Curtis, J. R., Orwoll, E. S., Barrett-Connor, E., Kado, D. M., Marshall, L. M., Shikany, J. M., Schousboe, J. T. 2016; 31 (8): 1500-3

  Abstract

  To determine the proportion of incident radiographic vertebral fractures (vfx) also diagnosed as incident clinical vfx in older men and vice-versa, we used data from 4398 community-dwelling men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study. Incident radiographic vfx were identified by comparing baseline and follow-up lateral thoracic and lumbar spine study films (average 4.6 years between films) using a semiquantitative (SQ) method and defined as a change in SQ reading of ≥1 at a given vertebral level from baseline to follow-up study radiograph. Participants were contacted triannually to ascertain incident clinical vfx; community spinal imaging studies were obtained and clinical vfx were confirmed when the study radiologist determined that the community imaging study showed a new deformity of higher grade than was present in the same vertebra on the baseline study radiograph. A total of 237 incident radiographic vfx were identified in 197 men, whereas 31 men experienced 37 confirmed incident clinical vfx. Of incident radiographic vfx, 13.5% were also clinically diagnosed as incident fractures, with clinical diagnoses made for 16.3% of the radiographic vfx with SQ grade change ≥2. Of incident clinical vfx, 86.5% were identified as incident radiographic vfx, most of them with SQ grade change ≥2. In summary, less than 15% of incident radiographic vfx were also clinically diagnosed, whereas the majority of incident clinical vfx were identified as severe radiographic vfx. These results in men supplement those previously published for women and suggest a complex relationship between clinical and radiographic vfx in older adults. Published 2016.(†) American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.2831

  View details for PubMedID 26969847

  View details for PubMedCentralID PMC5065098

• SHBG, Sex Steroids, and Kyphosis in Older Men: The MrOS Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Woods, G. N., Huang, M. H., Cawthon, P. M., Laughlin, G. A., Schousboe, J. T., McDaniels-Davidson, C., Cauley, J. A., Orwoll, E., Barrett-Connor, E., Kado, D. M. 2016; 31 (12): 2123-2128

  Abstract

  Accentuated kyphosis is associated with adverse health outcomes, including falls and fractures. Low bone density is a risk factor for hyperkyphosis, and each vertebral fracture adds roughly 4° to forward spine curvature. Sex steroids, in particular low bioavailable estradiol and high sex hormone-binding globulin (SHBG), are associated with bone loss and high SHBG is associated with vertebral fractures in older men. We, therefore, hypothesized that low bioavailable estradiol and high SHBG would be associated with worse kyphosis. To test this hypothesis, we examined the cross-sectional associations between individual bioavailable sex hormones and SHBG with radiographically assessed kyphosis. Participants included 1500 men aged 65 and older from the Osteoporotic Fractures in Men (MrOS) Study, in whom baseline measures of kyphosis and sex hormones were available. Modified Cobb angle of kyphosis, calculated from T4 through T12, was assessed from supine lateral spine radiographs. Serum total estradiol and total testosterone were measured by mass spectrometry, and bioavailable sex steroids were calculated from mass action equations. After adjustment for age and other confounding variables, no association was found between bioavailable estradiol or testosterone and Cobb angle, either when kyphosis was analyzed as a continuous variable or dichotomized into highest versus lower three quartiles. In linear regression models adjusted for age and clinic site, there was a significant association between SHBG and kyphosis (parameter estimate = 0.76 per SD increase, p = 0.01). In the fully adjusted model, this association was weakened and of only borderline statistical significance (parameter estimate = 0.61 per SD, p = 0.05). Logistic models demonstrated similar findings. Although associated with bone loss, we did not demonstrate that low bioavailable estradiol translates into worse kyphosis in older men. High SHBG is associated with bone loss and vertebral fractures. Our results suggest that high SHBG may also be a risk factor for hyperkyphosis. © 2016 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.2901

  View details for PubMedID 27355438

  View details for PubMedCentralID PMC5279779

• Evaluation of the Usefulness of Consensus Definitions of Sarcopenia in Older Men: Results from the Observational Osteoporotic Fractures in Men Cohort Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Cawthon, P. M., Blackwell, T. L., Cauley, J., Kado, D. M., Barrett-Connor, E., Lee, C. G., Hoffman, A. R., Nevitt, M., Stefanick, M. L., Lane, N. E., Ensrud, K. E., Cummings, S. R., Orwoll, E. S. 2015; 63 (11): 2247-2259

  Abstract

  To evaluate the associations between definitions of sarcopenia and clinical outcomes and the ability of the definitions to discriminate those with a high likelihood of having these outcomes from those with a low likelihood.Osteoporotic Fractures in Men Study.Six clinical centers.Community-dwelling men aged 65 and older (N = 5,934).Sarcopenia definitions from the International Working Group, European Working Group on Sarcopenia in Older Persons, Foundation for the National Institutes of Health Sarcopenia Project, Baumgartner, and Newman were evaluated. Recurrent falls were defined as two or more self-reported falls in the year after baseline (n = 694, 11.9%). Incident hip fractures (n = 207, 3.5%) and deaths (n = 2,003, 34.1%) were confirmed according to central review of medical records over 9.8 years. Self-reported functional limitations were assessed at baseline and 4.6 years later. Logistic regression or proportional hazards models were used to estimate associations between sarcopenia and falls, hip fractures, and death. The discriminative ability of the sarcopenia definitions (vs reference models) for these outcomes was evaluated using area under the receiver operating characteristic curve or C-statistics. Referent models included age alone for falls, functional limitations and mortality, and age and bone mineral density for hip fractures.The association between sarcopenia according to the various definitions and risk of falls, functional limitations, and hip fractures was variable; all definitions were associated with greater risk of death, but none of the definitions materially changed discrimination based on the AUC and C-statistic when compared with reference models (change ≤1% in all models).Sarcopenia definitions as currently constructed did not consistently improve prediction of clinical outcomes in relatively healthy older men.

  View details for DOI 10.1111/jgs.13788

  View details for PubMedID 26502831

• Risk of Nonspine Fractures in Older Adults with Sarcopenia, Low Bone Mass, or Both JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Chalhoub, D., Cawthon, P. M., Ensrud, K. E., Stefanick, M. L., Kado, D. M., Boudreau, R., Greenspan, S., Newman, A. B., Zmuda, J., Orwoll, E. S., Cauley, J. A. 2015; 63 (9): 1733-1740

  Abstract

  To test the hypothesis that men and women with low bone mineral density (BMD) and sarcopenia have a higher risk of fracture than those with only one or neither conditions.The Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures in women are prospective observational studies with a mean follow up of 9 (2000-2012) and 8 years (1997-2009), respectively.U.S. clinical centers.Men (n = 5,544; mean age 73.7) and women (n = 1,114; mean age 77.6) aged 65 and older, able to walk without assistance, and without bilateral hip replacement.Sarcopenia was defined as low appendicular lean mass plus slowness or weakness and low BMD according to the World Health Organization definition of a T-score less than -1.0. Participants were classified as having normal BMD and no sarcopenia (3,367 men, 308 women), sarcopenia only (79 men, 48 women), low BMD only (1,986 men, 626 women), and low BMD and sarcopenia (112 men, 132 women).Men with low BMD and sarcopenia (hazard ratio (HR)=3.79, 95% confidence interval (CI)=2.65-5.41) and men with low BMD only (HR=1.67, 95% CI=1.45-1.93) but not men with sarcopenia only (HR=1.14, 95% CI=0.62-2.09) had greater risk of fracture than men with normal BMD and no sarcopenia. Women with low BMD and sarcopenia (HR=2.27, 95% CI=1.37-3.76) and women with low BMD alone (HR=2.62, 95% CI=1.74-3.95), but not women with only sarcopenia, had greater risk of fracture than women with normal BMD and no sarcopenia.Men with low BMD and sarcopenia are at especially high risk of fracture. Sarcopenia alone did not increase fracture risk in either group.

  View details for DOI 10.1111/jgs.13605

  View details for PubMedID 26310882

• Spatial Cognition in Adult and Aged Mice Exposed to High-Fat Diet. PloS one Kesby, J. P., Kim, J. J., Scadeng, M., Woods, G., Kado, D. M., Olefsky, J. M., Jeste, D. V., Achim, C. L., Semenova, S. 2015; 10 (10): e0140034

  Abstract

  Aging is associated with a decline in multiple aspects of cognitive function, with spatial cognition being particularly sensitive to age-related decline. Environmental stressors, such as high-fat diet (HFD) exposure, that produce a diabetic phenotype and metabolic dysfunction may indirectly lead to exacerbated brain aging and promote the development of cognitive deficits. The present work investigated whether exposure to HFD exacerbates age-related cognitive deficits in adult versus aged mice. Adult (5 months old) and aged (15 months old) mice were exposed to control diet or HFD for three months prior to, and throughout, behavioral testing. Anxiety-like behavior in the light-dark box test, discrimination learning and memory in the novel object/place recognition tests, and spatial learning and memory in the Barnes maze test were assessed. HFD resulted in significant gains in body weight and fat mass content with adult mice gaining significantly more weight and adipose tissue due to HFD than aged mice. Weight gain was attributed to food calories sourced from fat, but not total calorie intake. HFD increased fasting insulin levels in all mice, but adult mice showed a greater increase relative to aged mice. Behaviorally, HFD increased anxiety-like behavior in adult but not aged mice without significantly affecting spatial cognition. In contrast, aged mice fed either control or HFD diet displayed deficits in novel place discrimination and spatial learning. Our results suggest that adult mice are more susceptible to the physiological and anxiety-like effects of HFD consumption than aged mice, while aged mice displayed deficits in spatial cognition regardless of dietary influence. We conclude that although HFD induces systemic metabolic dysfunction in both adult and aged mice, overall cognitive function was not adversely affected under the current experimental conditions.

  View details for DOI 10.1371/journal.pone.0140034

  View details for PubMedID 26448649

  View details for PubMedCentralID PMC4598128

• Physical function in older men with hyperkyphosis. The journals of gerontology. Series A, Biological sciences and medical sciences Katzman, W. B., Harrison, S. L., Fink, H. A., Marshall, L. M., Orwoll, E., Barrett-Connor, E., Cawthon, P. M., Kado, D. M. 2015; 70 (5): 635-40

  Abstract

  Age-related hyperkyphosis has been associated with poor physical function and is a well-established predictor of adverse health outcomes in older women, but its impact on health in older men is less well understood.We conducted a cross-sectional study to evaluate the association of hyperkyphosis and physical function in 2,363 men, aged 71-98 (M = 79) from the Osteoporotic Fractures in Men Study. Kyphosis was measured using the Rancho Bernardo Study block method. Measurements of grip strength and lower extremity function, including gait speed over 6 m, narrow walk (measure of dynamic balance), repeated chair stands ability and time, and lower extremity power (Nottingham Power Rig) were included separately as primary outcomes. We investigated associations of kyphosis and each outcome in age-adjusted and multivariable linear or logistic regression models, controlling for age, clinic, education, race, bone mineral density, height, weight, diabetes, and physical activity.In multivariate linear regression, we observed a dose-related response of worse scores on each lower extremity physical function test as number of blocks increased, p for trend ≤.001. Using a cutoff of ≥4 blocks, 20% (N = 469) of men were characterized with hyperkyphosis. In multivariate logistic regression, men with hyperkyphosis had increased odds (range 1.5-1.8) of being in the worst quartile of performing lower extremity physical function tasks (p < .001 for each outcome). Kyphosis was not associated with grip strength in any multivariate analysis.Hyperkyphosis is associated with impaired lower extremity physical function in older men. Further studies are needed to determine the direction of causality.

  View details for DOI 10.1093/gerona/glu213

  View details for PubMedID 25431353

  View details for PubMedCentralID PMC4400397

• Kyphosis and Sleep Characteristics in Older Persons: The Rancho Bernardo Study. Journal of sleep disorders and management Wankie, C., Kritz-Silverstein, D., Barrett-Connor, E., Kado, D. M. 2015; 1 (1)

  Abstract

  Kyphosis is a forward curvature of the thoracic spine that is associated with multiple adverse health outcomes. This cross-sectional study examined the association between kyphosis and sleep characteristics.Participants were 468 white, community-dwelling individuals (women = 255; men = 213) from the Rancho Bernardo cohort who had kyphosis assessed using a flexicurve ruler at a 2007-09 follow-up research clinic visit and sleep quality assessed by mailed survey in 2010 with the Pittsburgh Sleep Quality Index (PSQI), scored 0-18, with >5 indicative of poor sleep quality.Women had a mean age of 73.3 ± 8.8 years; men 74.2 ± 8.1 years. Mean flexicurve measures were 12.6 ± 3.2 for women and 12.1 ± 2.6 for men. No significant associations were found between kyphosis and any self-reported sleep measure in men, but women with worse kyphosis had poorer sleep quality, based on total PSQI score and two PSQI subcomponents. In women, with each unit increase in kyphosis, after adjusting for age, marital status, height, general health, calcium supplement use, estrogen use, exercise, arthritis, and depression, there was an associated increase in total PSQI score, indicating worse sleep quality (standard β-estimate = 1.37, 95% CI: 1.03, 1.82). Women with worse kyphosis were also more likely to sleep ≤ 7 hours (Odds Ratio (OR) = 1.11, 95% CI: 1.02, 1.22) and report use of sleep medications (OR = 1.14, 95% CI: 1.03, 1.25).In women only, those with worse flexicurve kyphosis had worse scores on the PSQI, slept fewer hours (≤ 7 hours) and were more likely to report sleep medication use than those with less kyphosis. The association between kyphosis and objective sleep measures in older persons deserves further investigation.

  View details for DOI 10.23937/2572-4053.1510004

  View details for PubMedID 28480455

  View details for PubMedCentralID PMC5419044

• Risk factors for hip fracture in older men: The Osteoporotic Fractures in Men Study (MrOS). Cauley, J., Cawthon, P., Peters, K., Cummings, S., Ensrud, K., Bauer, D., Taylor, B., Shikany, J. M., Hoffman, A., Lane, N., Kado, D., Orwoll, E. WILEY-BLACKWELL. 2014: S452

  View details for Web of Science ID 000356598702482

• Hyperkyphosis, kyphosis progression, and risk of non-spine fractures in older community dwelling women: the study of osteoporotic fractures (SOF). Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Kado, D. M., Miller-Martinez, D., Lui, L. Y., Cawthon, P., Katzman, W. B., Hillier, T. A., Fink, H. A., Ensrud, K. E. 2014; 29 (10): 2210-6

  Abstract

  While accentuated kyphosis is associated with osteoporosis, it is unknown whether it increases risk of future fractures, independent of bone mineral density (BMD) and vertebral fractures. We examined the associations of baseline Cobb angle kyphosis and 15 year change in kyphosis with incident non-spine fractures using data from the Study of Osteoporotic Fractures. A total of 994 predominantly white women, aged 65 or older, were randomly sampled from 9704 original participants to have repeated Cobb angle measurements of kyphosis measured from lateral spine radiographs at baseline and an average of 15 years later. Non-spine fractures, confirmed by radiographic report, were assessed every 4 months for up to 21.3 years. Compared with women in the lower three quartiles of kyphosis, women with kyphosis greater than 53° (top quartile) had a 50% increased risk of non-spine fracture (95% CI, 1.10-2.06 after adjusting for BMD, prevalent vertebral fractures, prior history of fractures, and other fracture risk factors. Cobb angle kyphosis progressed an average of 7° (SD = 6.8) over 15 years. Per 1 SD increase in kyphosis change, there was a multivariable adjusted 28% increased risk of fracture (95% CI, 1.06-1.55) that was attenuated by further adjustment for baseline BMD (HR per SD increase in kyphosis change, 1.19; 95% CI 0.99-1.44). Greater kyphosis is associated with an elevated non-spine fracture risk independent of traditional fracture risk factors in older women. Furthermore, worsening kyphosis is also associated with increased fracture risk that is partially mediated by low baseline BMD that itself is a risk factor for kyphosis progression. These results suggest that randomized controlled fracture intervention trials should consider implementing kyphosis measures to the following: (1) further study kyphosis and kyphosis change as an additional fracture risk factor; and (2) test whether therapies may improve or delay its progression.

  View details for DOI 10.1002/jbmr.2251

  View details for PubMedID 24715607

  View details for PubMedCentralID PMC4177348

• Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the Osteoporotic Fractures in Men (MrOS) research group. BMC musculoskeletal disorders Katzman, W. B., Miller-Martinez, D., Marshall, L. M., Lane, N. E., Kado, D. M. 2014; 15: 19

  Abstract

  The prevalence of hyperkyphosis is increased in older men; however, risk factors other than age and vertebral fractures are not well established. We previously reported that poor paraspinal muscle composition contributes to more severe kyphosis in a cohort of both older men and women.To specifically evaluate this association in older men, we conducted a cross-sectional study to evaluate the association of paraspinal muscle composition and degree of thoracic kyphosis in an analytic cohort of 475 randomly selected participants from the Osteoporotic Fractures in Men (MrOS) study with baseline abdominal quantitative computed tomography (QCT) scans and plain thoracic radiographs. Baseline abdominal QCT scans were used to obtain abdominal body composition measurements of paraspinal muscle and adipose tissue distribution. Supine lateral spine radiographs were used to measure Cobb angle of kyphosis. We examined the linear association of muscle volume, fat volume and kyphosis using loess plots. Multivariate linear models were used to investigate the association between muscle and kyphosis using total muscle volume, as well as individual components of the total muscle volume, including adipose and muscle compartments alone, controlling for age, height, vertebral fractures, and total hip bone mineral density (BMD). We examined these associations among those with no prevalent vertebral fracture and those with BMI < 30 kg/m2.Among men in the analytic cohort, means (SD) were 74 (SD = 5.9) years for age, and 37.5 (SD = 11.9) degrees for Cobb angle of kyphosis. Men in the lowest tertile of total paraspinal muscle volume had greater mean Cobb angle than men in the highest tertile, although test of linear trend across tertiles did not reach statistical significance. Neither lower paraspinal skeletal muscle volume (p-trend = 0.08), or IMAT (p-trend = 0.96) was associated with greater kyphosis. Results were similar among those with no prevalent vertebral fractures. However, among men with BMI < 30 kg/m2, those in the lowest tertile of paraspinal muscle volume had greater adjusted mean kyphosis (40.0, 95% CI: 37.8 - 42.1) compared to the highest tertile (36.3, 95% CI: 34.2 - 38.4).These results suggest that differences in body composition may potentially influence kyphosis.

  View details for DOI 10.1186/1471-2474-15-19

  View details for PubMedID 24428860

  View details for PubMedCentralID PMC4029749

• Prediction models of prevalent radiographic vertebral fractures among older women. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry Schousboe, J. T., Rosen, H. R., Vokes, T. J., Cauley, J. A., Cummings, S. R., Nevitt, M., Black, D. M., Orwoll, E. S., Kado, D. M., Ensrud, K. E. 2014; 17 (3): 378-85

  Abstract

  It is unknown how well prediction models incorporating multiple risk factors identify women with radiographic prevalent vertebral fracture (PVFx) compared with simpler models and what their value might be in clinical practice to select older women for lateral spine imaging. We compared 4 regression models for predicting PVFx in women aged 68 y and older enrolled in the Study of Osteoporotic Fractures with a femoral neck T-score ≤ -1.0, using area under receiving operator characteristic curves (AUROC) and a net reclassification index. The AUROC for a model with age, femoral neck bone mineral density, historical height loss (HHL), prior nonspine fracture, body mass index, back pain, and grip strength was only minimally better than that of a more parsimonious model with age, femoral neck bone mineral density, and historical height loss (AUROC 0.689 vs 0.679, p values for difference in 5 bootstrapped samples <0.001-0.35). The prevalence of PVFx among this older population of Caucasian women remained more than 20% even when women with low probability of PVFx, as estimated by the prediction models, were included in the screened population. These results suggest that lateral spine imaging is appropriate to consider for all Caucasian women aged 70 y and older with low bone mass to identify those with PVFx.

  View details for DOI 10.1016/j.jocd.2013.09.021

  View details for PubMedID 24582085

  View details for PubMedCentralID PMC4119570

• Prevalent Vertebral Fractures Predict Risk of Vertebral and Non-Vertebral Fractures in Older Men: the MrOS Study Black, D., Peters, K., Cawthon, P., Cauley, J., Cummings, S., Orwoll, E., Ensrud, K., Fink, H., Marshall, L., Parimi, N., Kado, D., Stefanick, M., Schousboe, J. WILEY-BLACKWELL. 2013

  View details for Web of Science ID 000332035805106

• Sex Steroid Hormones and Kyphosis in Older Men: The Osteoporotic Fractures in Men (MrOS) Study Kado, D., Huang, M., McDaniels-Davidson, C., Laughlin, G., Cauley, J., Orwoll, E., Lane, N., Stefanick, M., Barrett-Connor, E., Cawthon, P. WILEY-BLACKWELL. 2013

  View details for Web of Science ID 000332035802178

• Risk of Non-spine Fractures Among Men and Women with Sarcopenia, Low Bone Mass or Both Chalhoub, D., Cawthon, P., Ensrud, K., Stefanick, M., Kado, D., Orwoll, E., Cauley, J. WILEY-BLACKWELL. 2013

  View details for Web of Science ID 000332035800004

• Prediction models of prevalent radiographic vertebral fractures among older men. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry Schousboe, J. T., Rosen, H. R., Vokes, T. J., Cauley, J. A., Cummings, S. R., Nevitt, M. C., Black, D. M., Orwoll, E. S., Kado, D. M., Ensrud, K. E. 2013; 17 (4): 449-57

  Abstract

  No studies have compared how well different prediction models discriminate older men who have a radiographic prevalent vertebral fracture (PVFx) from those who do not. We used area under receiver operating characteristic curves and a net reclassification index to compare how well regression-derived prediction models and nonregression prediction tools identify PVFx among men age ≥65 yr with femoral neck T-score of -1.0 or less enrolled in the Osteoporotic Fractures in Men Study. The area under receiver operating characteristic for a model with age, bone mineral density, and historical height loss (HHL) was 0.682 compared with 0.692 for a complex model with age, bone mineral density, HHL, prior non-spine fracture, body mass index, back pain, grip strength, smoking, and glucocorticoid use (p values for difference in 5 bootstrapped samples 0.14-0.92). This complex model, using a cutpoint prevalence of 5%, correctly reclassified only a net 5.7% (p = 0.13) of men as having or not having a PVFx compared with a simple criteria list (age ≥ 80 yr, HHL >4 cm, or glucocorticoid use). In conclusion, simple criteria identify older men with PVFx and regression-based models. Future research to identify additional risk factors that more accurately identify older men with PVFx is needed.

  View details for DOI 10.1016/j.jocd.2013.09.020

  View details for PubMedID 24289883

  View details for PubMedCentralID PMC4035457

• Association of serum fibroblast growth factor 23 (FGF23) and incident fractures in older men: the Osteoporotic Fractures in Men (MrOS) study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Lane, N. E., Parimi, N., Corr, M., Yao, W., Cauley, J. A., Nielson, C. M., Ix, J. H., Kado, D., Orwoll, E. 2013; 28 (11): 2325-32

  Abstract

  Normal mineral metabolism is critical for skeletal integrity, and recently serum fibroblast growth factor 23 (FGF23) levels were found to be directly related to overall fracture risk in elderly Swedish men. To confirm this association, we performed a prospective case-cohort study to understand the relation of FGF23 and fracture risk in older white men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men attending the baseline MrOS examination, we evaluated a subgroup of 387 men with incident nonvertebral fracture including 73 hip fractures and a sample of 1385 men randomly selected from the cohort with baseline mineral and calcium hormone measurements. FGF23 was measured in baseline serum samples by ELISA (Millipore, Billerica, MA, USA). Modified Cox proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of fracture in men across quartiles of FGF23. Subjects were also stratified by renal function, and RH per strata was estimated in men with the highest quartile of FGF23 compared with quartiles 3, 2, and 1. Overall, there was no difference in risk of nonspine or hip fracture by baseline FGF23. However, associations differed by strata of eGFRCrCy . Among men with eGFRCrCys <60 mL/min/1.73 m2 (n = 73/313 nonspine fractures), the RH in the highest quartile of FGF23 compared with the rest was 2.02 (95% confidence interval [CI] 1.07-3.79), but in men with eGFRCrCy , >60 mL/min/1.73 m2 (304/1370 fractures) the RH was 0.91 (95% CI 0.66-1.25) after adjustment for age, clinic site, body mass index, race, total hip bone mineral density, vitamin D, parathyroid hormone, alcohol use, physical activity, fracture history, and serum phosphorus. Serum FGF23 levels are not associated with incident fractures in elderly men overall. However, higher levels of serum FGF23 are associated with fracture risk in those with poor renal function.

  View details for DOI 10.1002/jbmr.1985

  View details for PubMedID 23677793

  View details for PubMedCentralID PMC3805817

• Kyphosis and decline in physical function over 15 years in older community-dwelling women: the Study of Osteoporotic Fractures. The journals of gerontology. Series A, Biological sciences and medical sciences Katzman, W. B., Huang, M. H., Lane, N. E., Ensrud, K. E., Kado, D. M. 2013; 68 (8): 976-83

  Abstract

  Maintaining physical function is an important prerequisite for preserving independence in later life. Greater degrees of kyphosis in the thoracic spine are prevalent in older persons and accompanied by reduced physical function in multiple cross-sectional studies. It is unknown whether kyphosis predicts worse physical function over time.We retrospectively assessed whether greater magnitude of kyphosis is associated with decline in self-reported and objectively measured physical function over 15 years. Digitized Cobb angle kyphosis (T4-T12) was derived from supine lateral thoracic spine radiographs in a cohort of 1,196 women aged 65 and older (mean = 69.3 years [SD = 4.0]). Using regression models, we evaluated associations of baseline kyphosis with both self-reported functional status and objectively measured gait speed, grip strength, and timed chair stands cross-sectionally and as change assessed over 15 years.In cross-sectional multivariate analyses, with each 10-degree increment of kyphosis, grip strength was 0.24 kg lower (p = .02), but there were no significant associations between kyphosis and functional status, gait speed, or timed chair stand, likely reflecting the high functioning study participants. In multivariate longitudinal analysis, with each 10-degree increment in baseline kyphosis, there was 0.07 point additional decline in functional status (p = .09), 0.01 m/s more decline in gait speed (p = .07), and 0.32 s greater decline in time to complete five chair stands (p = .004), but no association with decline in grip strength.Greater magnitude of kyphosis may predict worsening lower extremity function over time in older women. Early recognition and preventative measures against kyphosis progression may help preserve physical function over the long term.

  View details for DOI 10.1093/gerona/glt009

  View details for PubMedID 23633167

  View details for PubMedCentralID PMC3712361

• Factors associated with kyphosis progression in older women: 15 years' experience in the study of osteoporotic fractures. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Kado, D. M., Huang, M. H., Karlamangla, A. S., Cawthon, P., Katzman, W., Hillier, T. A., Ensrud, K., Cummings, S. R. 2013; 28 (1): 179-87

  Abstract

  Age-related hyperkyphosis is thought to be a result of underlying vertebral fractures, but studies suggest that among the most hyperkyphotic women, only one in three have underlying radiographic vertebral fractures. Although commonly observed, there is no widely accepted definition of hyperkyphosis in older persons, and other than vertebral fracture, no major causes have been identified. To identify important correlates of kyphosis and risk factors for its progression over time, we conducted a 15-year retrospective cohort study of 1196 women, aged 65 years and older at baseline (1986 to 1988), from four communities across the United States: Baltimore County, MD; Minneapolis, MN; Portland, OR; and the Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs obtained at baseline and an average of 3.7 and 15 years later. Repeated measures, mixed effects analyses were performed. At baseline, the mean kyphosis angle was 44.7 degrees (SE = 0.4, SD = 11.9) and significant correlates included a family history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density, greater body weight, degenerative disc disease, and smoking. Over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age-related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss.

  View details for DOI 10.1002/jbmr.1728

  View details for PubMedID 22865329

  View details for PubMedCentralID PMC3693545

• Active Referral Intervention following Fragility Fractures Leads to Enhanced Osteoporosis Follow-Up Care. Journal of osteoporosis Sugi, M. T., Sheridan, K., Lewis, L., Huang, M. H., Nattiv, A., Kado, D. M., Bengs, B. 2012; 2012: 234381

  Abstract

  At one major urban academic medical center, patients aged 50 years and older with fragility fractures were identified and scheduled or assisted in referral into osteoporosis medical management appointments. We evaluated the efficacy of an active intervention program at overcoming the logistical barriers and improving proper osteoporosis follow-up for persons who have sustained a fragility fracture. Of 681 patients treated for defined fractures, 168 were eligible and consented for the study of fragility fractures. Of those enrolled, 91 (54.2%) had appropriate osteoporosis follow-up on initial interview, and overall 120 (71.4%) had successful osteoporosis follow-up following our active intervention. Seventy patients (41.7%) were deemed to have no osteoporosis follow-up, and, of these, 48 were successfully referred to a scheduling coordinator. The scheduling coordinator was able to contact 37 (77%) patients to schedule proper follow-up, and, of these, 29 (78.4%) confirmed receiving an appropriate follow-up appointment. Active intervention and assisted scheduling for patients with recent fragility fractures improved the self-reported rate of osteoporosis follow-up from 54.2% to 71.4%.

  View details for DOI 10.1155/2012/234381

  View details for PubMedID 22523716

  View details for PubMedCentralID PMC3317124

• Height loss in older women: risk of hip fracture and mortality independent of vertebral fractures. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Hillier, T. A., Lui, L. Y., Kado, D. M., LeBlanc, E. S., Vesco, K. K., Bauer, D. C., Cauley, J. A., Ensrud, K. E., Black, D. M., Hochberg, M. C., Cummings, S. R. 2012; 27 (1): 153-9

  Abstract

  We examined if height loss in older women predicts risk of hip fractures, other nonspine fractures, and mortality, and whether this risk is independent of both vertebral fractures (VFx) and bone mineral density (BMD) by dual-energy X-ray absorptiometry. Among 3124 women age 65 and older in the Study of Osteoporotic Fractures, we assessed the association with measured height change between year 0 (1986-1988) and year 15 (2002-2004) and subsequent risk of radiologically confirmed hip fractures, other nonspine fractures, and mortality assessed via death certificates. Follow-up occurred every 4 months for fractures and vital status (>95% contacts complete). Cox proportional hazards models assessed risk of hip fracture, nonspine fracture, and mortality over a mean of 5 years after height change was assessed (ie, after final height measurement). After adjustment for VFx, BMD, and other potential covariates, height loss >5 cm was associated with a marked increased risk of hip fracture [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.06, 2.12], nonspine fracture (HR 1.48; 95% CI 1.20, 1.83), and mortality (1.45; 95% CI 1.21, 1.73). Although primary analyses were a subset of 3124 survivors healthy enough to return for a year 15 height measurement, a sensitivity analysis in the entire cohort (n = 9677) using initial height in earlier adulthood [self-reported height at age 25 (-40 years) to measured height age >65 years (Year 0)] demonstrated consistent results. Height loss >5 cm (2″) in older women was associated with a nearly 50% increased risk of hip fracture, nonspine fracture, and mortality-independent of incident VFx and BMD.

  View details for DOI 10.1002/jbmr.558

  View details for PubMedID 22072593

  View details for PubMedCentralID PMC3622730

• Association of spinal muscle composition and prevalence of hyperkyphosis in healthy community-dwelling older men and women. The journals of gerontology. Series A, Biological sciences and medical sciences Katzman, W., Cawthon, P., Hicks, G. E., Vittinghoff, E., Shepherd, J., Cauley, J. A., Harris, T., Simonsick, E. M., Strotmeyer, E., Womack, C., Kado, D. M. 2012; 67 (2): 191-5

  Abstract

  Older adults with hyperkyphosis are at increased risk of falls, fractures, and functional decline. Modifiable risk factors for hyperkyphosis have not been well studied. Our objective was to determine whether spinal muscle area and density are associated with hyperkyphosis, independent of age, race, sex, bone mineral density, and trunk fat.Using data from the Pittsburgh site of the Health, Aging, and Body Composition study, we performed a baseline cross-sectional analysis. Participants were black and white men and women 70-79 years old (N = 1172), independent in activities of daily living and able to walk ¼ mile and up 10 steps without resting. We measured Cobb's angle of kyphosis from supine lateral scout computed tomography scans, and categorized hyperkyphosis as Cobb's angle >40°. Axial images from lateral scout computed tomography scans assessed spinal extensor muscle cross-sectional area and density (proxy for fat infiltration).In our sample, 21% had hyperkyphosis. Prevalence in black men was 11%; in white men, 17%; in black women, 26%; and in white women, 30%. In multivariate analysis, each standard deviation increase in muscle density was associated with a 29% reduction in the odds of hyperkyphosis, independent of covariates. Muscle area was not significantly associated with hyperkyphosis.Lower spinal muscle density is associated with hyperkyphosis in healthy community-dwelling older adults. This potentially modifiable risk factor could be targeted in exercise interventions. Randomized trials are needed to determine whether an exercise program targeting spinal muscle density reduces hyperkyphosis and in turn improves health outcomes.

  View details for DOI 10.1093/gerona/glr160

  View details for PubMedID 21878482

  View details for PubMedCentralID PMC3297013

• Diffuse idiopathic skeletal hyperostosis and its relation to back pain among older men: the MrOS Study. Seminars in arthritis and rheumatism Holton, K. F., Denard, P. J., Yoo, J. U., Kado, D. M., Barrett-Connor, E., Marshall, L. M. 2011; 41 (2): 131-8

  Abstract

  To estimate the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in a cross-sectional study of elderly men age 65 to 100 years and to examine back and neck pain as possible correlates of DISH.DISH was defined using Resnick's criteria and scored according to Mata on lateral spine radiographs of 298 randomly selected participants from the MrOS Study. Standardized self-reported questionnaires were used to assess the frequency and severity of back and neck pain, and the relation of these to DISH status was estimated with χ(2) tests, as well as prevalence ratios and 95% confidence intervals using log-binomial regression models.DISH was observed in 126 older men (42%), increased with age (30%, 39%, 48%, and 56% for ages 65-69, 70-74, 75-79, and ≥80 respectively), and was positively associated with body mass index (BMI) (P = 0.04) and blood pressure (P = 0.02). Significantly less back pain in the past 12 months was reported among men with DISH as compared to men without (59% vs 71%, P = 0.03), which remained after adjustment for age, BMI, and blood pressure (prevalence ratios = 0.73, 95% confidence interval = 0.57-0.95). Back pain severity (P = 0.07) and frequency (P = 0.06) were also less frequent among men with DISH compared to men without, whereas reported neck pain was similar between groups (P = 0.39).Among community-dwelling elderly men, DISH prevalence is high, increases with age, and is positively associated with BMI and blood pressure. Frequency of self-reported back pain over the past 12 months was lower in older men with DISH as compared to those without DISH.

  View details for DOI 10.1016/j.semarthrit.2011.01.001

  View details for PubMedID 21377195

  View details for PubMedCentralID PMC3128652

• Age-related hyperkyphosis, independent of spinal osteoporosis, is associated with impaired mobility in older community-dwelling women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA Katzman, W. B., Vittinghoff, E., Kado, D. M. 2011; 22 (1): 85-90

  Abstract

  While many assume hyperkyphosis reflects underlying spinal osteoporosis and vertebral fractures, our results suggest hyperkyphosis is independently associated with decreased mobility. Hyperyphosis is associated with slower Timed Up and Go performance times and may be a useful clinical marker signaling the need for evaluation of vertebral fracture and falling risk.While multiple studies have demonstrated negative effects of hyperkyphosis on physical function, none have disentangled the relationship between hyperkyphosis, impaired function, and underlying spinal osteoporosis. The purpose of this study is to determine whether kyphosis, independent of spinal osteoporosis, is associated with mobility on the Timed Up and Go, and to quantify effects of other factors contributing to impaired mobility.We used data for 3,108 community-dwelling women aged 55-80 years in the Fracture Intervention Trial. All participants had measurements of kyphosis, mobility time on the Timed Up and Go test, height, weight, total hip bone mineral density (BMD), grip strength, and vertebral fractures at baseline visits in 1993. Demographic characteristics included age and smoking status. We calculated mean Timed Up and Go time by quartile of kyphosis. Using multivariate linear regression, we estimated the independent association of kyphosis with mobility time, and quantified effects of other covariates on mobility.Mean mobility time increased from 9.3 s in the lowest to 10.1 s in the highest quartile of kyphosis. In a multivariate-adjusted model, mobility time increased 0.11 s (p = 0.02) for each standard deviation (11.9°) increase in kyphosis. Longer performance times were significantly associated with increasing age, decreasing grip strength, vertebral fractures, body mass index ≥25, and total hip BMD in the osteoporotic range.Kyphosis angle is independently associated with decreased mobility on the Timed Up and Go, which is in turn correlated with increased fall risk. Hyperkyphosis may be a useful clinical marker signaling the need for evaluation of vertebral fracture and falling risk.

  View details for DOI 10.1007/s00198-010-1265-7

  View details for PubMedID 20480146

  View details for PubMedCentralID PMC2958231

• Do the effects of APOE-ε4 on cognitive function and decline depend upon vitamin status? MacArthur Studies of Successful Aging. The journal of nutrition, health & aging Brown, B., Huang, M. H., Karlamangla, A., Seeman, T., Kado, D. 2011; 15 (3): 196-201

  Abstract

  To investigate whether gene nutrient interactions influence the risk of cognitive dysfunction among older persons.We performed a cross-sectional and longitudinal study of 499 adults aged 70-79 years from the Mac Arthur Study of Successful Aging to determine the effect of apolipoprotein E (APOE) in conjunction with plasma levels of homocysteine and of the related B vitamins on multiple domains of cognitive function and cognitive decline.The APOE-ε4 allele, high homocysteine, low folate, and low vitamin B6 levels were each associated with worse baseline cognitive function, and all but B6 and B12 were associated with seven year cognitive decline. There was no interaction between APOE-ε4, and homocysteine, folate, B6, or B12 in predicting baseline cognitive function (p-values: 0.12-0.94) or longitudinal decline (p-values: 0.52-0.91). Of five cognitive subtests, there was a significant interaction between the ε4 allele, low B6, and decline in correct naming response items (p=0.04).B vitamin status does not influence the risk of overall cognitive dysfunction in ε4 allele affected older adults.

  View details for DOI 10.1007/s12603-010-0277-5

  View details for PubMedID 21369667

• Increasing kyphosis predicts worsening mobility in older community-dwelling women: a prospective cohort study. Journal of the American Geriatrics Society Katzman, W. B., Vittinghoff, E., Ensrud, K., Black, D. M., Kado, D. M. 2011; 59 (1): 96-100

  Abstract

  To determine whether increasing kyphosis angle was independently associated with poorer mobility as measured according to the Timed Up and Go Test (TUG), after controlling for other established risk factors.Prospective cohort study.Eleven clinical centers in the United States.Two thousand seven hundred seventy-seven women aged 55 to 80 randomized to the placebo arms of the Fracture Intervention Trial, a randomized controlled trial of the effect of alendronate on risk for osteoporotic fractures.The primary predictor was change in kyphosis angle, measured using the Debrunner Kyphometer; the outcome was change in mobility, measured as performance time on the TUG. Covariates were baseline age, kyphosis angle, body mass index (BMI), self-reported health status, grip strength, change in total hip bond mineral density (BMD), and number of vertebral fractures over a mean of 4.4 years.Greater kyphosis angle predicted longer mobility performance times (P<.001), independent of other significant predictors of worsening mobility including age, baseline kyphosis, health status, grip strength, BMI, change in hip BMD, and new vertebral fractures. TUG performance times increased by 0.02 seconds (95% confidence interval (CI)=0.01-0.03) for every 5° increase in kyphosis angle, more than the increase in mobility time of 0.01 seconds (95% CI=0.005-0.03) over 1 year observed in this cohort.Increasing kyphosis angle is independently associated with worsening mobility. Interventions are needed to prevent or reduce increasing kyphosis and mobility decline.

  View details for DOI 10.1111/j.1532-5415.2010.03214.x

  View details for PubMedID 21198460

  View details for PubMedCentralID PMC3696343

• Back pain, neurogenic symptoms, and physical function in relation to spondylolisthesis among elderly men. The spine journal : official journal of the North American Spine Society Denard, P. J., Holton, K. F., Miller, J., Fink, H. A., Kado, D. M., Marshall, L. M., Yoo, J. U. 2010; 10 (10): 865-73

  Abstract

  Degenerative spondylolisthesis is a presumed cause of back pain. Previous studies of spondylolisthesis and back pain included only women or combined results for men and women. Comparisons of the frequency of back pain, neurogenic symptoms, and functional limitations specifically among elderly men with and without spondylolisthesis are needed.To determine associations of prevalent spondylolisthesis with back pain symptoms, neurogenic symptoms, and functional limitations among elderly men.Cross-sectional epidemiologic study conducted within the Osteoporotic Fractures in Men (MrOS) cohort. The MrOS cohort is composed of 5,995 community-dwelling men aged 65 years or older who were recruited at six US academic medical centers. Extensive self-reported data and lumbar spine radiographs were obtained for all MrOS participants at baseline.For this study, 300 men were selected at random specifically for the evaluation of spondylolisthesis on the baseline spine radiographs.Standardized questionnaires were used to assess self-reported back pain, leg pain (radiculopathy), lower extremity numbness (paresthesias), and lower extremity weakness occurring in the past 12 months and to ascertain current difficulty with activities of daily living.In the present study, radiographic spondylolisthesis was classified as forward slip of ≥5%. Prevalence of back pain, neurogenic symptoms, and difficulty with activities of daily living was compared between men with and without spondylolisthesis using chi-square or Fisher exact tests.Spondylolisthesis was present among 92 (31%) men. Among men with and without spondylolisthesis, back pain (63% vs. 67%, p=.46) and moderate/severe back pain (41% vs. 38%, p=.76) were reported with similar frequency. Men with spondylolisthesis more often reported radiculopathy (33% vs. 22%, p=.06), paresthesias (18% vs. 11%, p=.10), and weakness (18% vs. 9%, p=.02) in the lower extremities, as well as difficulty walking two to three blocks (21% vs. 11%, p=.03), doing their own shopping (8% vs. 2%, p=.04), and getting in/out of a car (14% vs. 6%, p=.03), compared with men without spondylolisthesis.Among elderly men, spondylolisthesis was associated with neurogenic symptoms and lower extremity functional limitations; however, spondylolisthesis was not associated with a higher likelihood of back pain in this population.

  View details for DOI 10.1016/j.spinee.2010.07.004

  View details for PubMedID 20869000

  View details for PubMedCentralID PMC2946938

• Lumbar spondylolisthesis among elderly men: prevalence, correlates, and progression. Spine Denard, P. J., Holton, K. F., Miller, J., Fink, H. A., Kado, D. M., Yoo, J. U., Marshall, L. M. 2010; 35 (10): 1072-8

  Abstract

  Prospective cohort study. OBJECTIVE.: Estimate the prevalence of spondylolisthesis and determine the factors associated with higher or lower prevalence among men aged 65 years or older.Spondylolisthesis prevalence is reported to increase with age and to be higher among women than men. Among women aged > or =65 years, prevalence was estimated to be 29%, but no estimates among men of this age have been reported. METHODS.: Lateral lumbar spine radiographs were obtained at baseline and a follow-up visit in the Osteoporotic Fractures in Men (MrOS) study, a cohort of community dwelling men ages > or =65 years. Average time between radiographs was 4.6 (+/-0.4) years. For the present study, 300 men were sampled at random at baseline. Of these, 295 had a usable baseline radiograph; 190 surviving participants had a follow-up radiograph. Spondylolisthesis was defined as a forward slip > or =5%. Progression was defined as a 5% increase in slip severity on the follow-up radiograph. Associations of spondylolisthesis prevalence with baseline characteristics were estimated with age-adjusted prevalence ratios and 95% confidence intervals from log binomial regression models.The mean (SD) age of the men studied was 74 (+/-6) years. Prevalence of lumbar spondylolisthesis was 31%. Spondylolisthesis was observed at the L3/4, L4/5, and L5/S1 levels. In 96% with spondylolisthesis, only one vertebral level was involved. The degree of slip ranged from 5% to 28%, and nearly all listhesis was classified as Meyerding grade I. During follow-up, 12% of men with prevalent spondylolisthesis had progression; 12% without baseline spondylolisthesis had new onset. Prevalence did not vary by height, BMI, smoking history, diabetes, or heart disease. However, men with spondylolisthesis more often reported higher levels of physical activity or walking daily for exercise than men without spondylolisthesis.Spondylolisthesis may be more common among older men than previously recognized.

  View details for DOI 10.1097/BRS.0b013e3181bd9e19

  View details for PubMedID 20393398

  View details for PubMedCentralID PMC2903965

• The rehabilitation of hyperkyphotic posture in the elderly. European journal of physical and rehabilitation medicine Kado, D. M. 2009; 45 (4): 583-93

  Abstract

  The angle of thoracic kyphosis tends to increase with age resulting in hyperkyphosis in some individuals. While the term "kyphotic" is occasionally used to describe someone with accentuated thoracic curvature, hyperkyphosis is preferred since kyphosis itself refers to the normal sagittal angle of thoracic curvature. Epidemiolo-gic studies have demonstrated that age-related hyperkyphosis commonly affects the elderly population with estimates ranging from 20% to 40%. In addition, hyperkyphosis affects a substantial number of older men. Apart from being a cosmetic deformity, older persons who suffer from hyperkyphosis are at increased risk for a variety of adverse health outcomes that include poor physical function, pulmonary compromise, falls, fractures, and even earlier mortality. Most clinicians and patients have assumed that thoracic hyperkyphosis is a result of underlying spinal osteoporosis, but approximately two thirds of those who are most hyperkyphotic don't have vertebral fractures. Over the past few years, there has been increased awareness and focus on potential effective treatments for age-related hyperkyphosis. Of these treatments, exercise based interventions and spinal orthoses are conservative rehabilitation management techniques that have shown promise in potentially improving health outcomes for affected patients. To date, all of these types of trials have been small in scale, and most short in duration. In the future, larger rigorously designed clinical trials will be needed to test and confirm the efficacy and feasibility of the most promising treatments for age-related hyperkyphosis. This invited review will discuss hyperkyphosis in terms of its etiology, clinical associations, and treatment in elderly individuals.

  View details for PubMedID 20032918

• Hyperkyphosis predicts mortality independent of vertebral osteoporosis in older women. Annals of internal medicine Kado, D. M., Lui, L. Y., Ensrud, K. E., Fink, H. A., Karlamangla, A. S., Cummings, S. R. 2009; 150 (10): 681-7

  Abstract

  Excessive kyphosis may be associated with earlier mortality, but previous studies have not controlled for clinically silent vertebral fractures, which are a known mortality risk factor.To determine whether hyperkyphosis predicts increased mortality independent of vertebral fractures.Prospective cohort study.Four clinical centers in Baltimore County, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania.610 women, age 67 to 93 years, from a cohort of 9704 women recruited from community-based listings between 1986 and 1988.Kyphosis was measured by using a flexicurve. Prevalent radiographic vertebral fractures at baseline were defined by morphometry, and mortality was assessed during an average follow-up of 13.5 years.In age-adjusted models, each SD increase in kyphosis carried a 1.14-fold increased risk for death (95% CI, 1.02 to 1.27; P = 0.023). After adjustment for age and other predictors of mortality, including such osteoporosis-related factors as low bone density, moderate and severe prevalent vertebral fractures, and number of prevalent vertebral fractures, women with greater kyphosis were at increased risk for earlier death (relative hazard per SD increase, 1.15 [CI, 1.01 to 1.30]; P = 0.029). On stratification by prevalent vertebral fracture status, only women with prevalent fractures were at increased mortality risk from hyperkyphosis, independent of age, self-reported health, smoking, spine bone mineral density, number of vertebral fractures, and severe vertebral fractures (relative hazard per SD increase, 1.58 [CI, 1.06 to 2.35]; P = 0.024).The study population included only white women.In older women with vertebral fractures, hyperkyphosis predicts an increased risk for death, independent of underlying spinal osteoporosis and the extent and severity of vertebral fractures.National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging.

  View details for PubMedID 19451575

  View details for PubMedCentralID PMC2711520

• Light to moderate alcohol consumption and disability: variable benefits by health status. American journal of epidemiology Karlamangla, A. S., Sarkisian, C. A., Kado, D. M., Dedes, H., Liao, D. H., Kim, S., Reuben, D. B., Greendale, G. A., Moore, A. A. 2009; 169 (1): 96-104

  Abstract

  In adults, light to moderate alcohol consumption is associated with lower risks for heart disease, diabetes, and mortality. This study examined whether light to moderate alcohol use is also associated with lower risk of incident physical disability over two 5-year periods in 4,276 noninstitutionalized adults in the United States, aged 50 years or older, by using data from 3 waves of the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study surveys from 1982 to 1992. Light/moderate drinking (<15 drinks per week and <5 per drinking day or 4 per drinking day for women) was associated with reduced risk for incident disability or death over 5 years, compared with abstention (adjusted odds ratio = 0.77; P = 0.008). Among survivors, light/moderate drinking was associated with lower risk for incident disability, compared with abstention (adjusted odds ratio = 0.75; P = 0.009). In stratified analyses, disability risk decreased with light/moderate drinking in a dose-dependent fashion in men and women with good or better self-reported health but not in men or women with fair or worse self-reported health. Alcohol consumption in moderation might reduce the risk of developing physical disability in older adults in good health but not in those in poor health.

  View details for DOI 10.1093/aje/kwn294

  View details for PubMedID 19022829

  View details for PubMedCentralID PMC2720706

• Narrative review: hyperkyphosis in older persons. Annals of internal medicine Kado, D. M., Prenovost, K., Crandall, C. 2007; 147 (5): 330-8

  Abstract

  Hyperkyphosis is a widely recognized yet largely ignored condition. Although there are no uniform diagnostic criteria for hyperkyphosis, current studies estimate its prevalence among older adults at 20% to 40%. The causes and consequences of hyperkyphosis are not well understood. Some physicians think that fractures cause hyperkyphosis and that management strategies should focus solely on diagnosis and treatment for osteoporosis. Recent studies, however, demonstrate that many older adults who are most affected by hyperkyphosis do not have vertebral fractures. Hyperkyphosis may be independently associated with an increased risk for adverse health outcomes, including impaired pulmonary function, decreased physical function capabilities, and future fractures. With the growing older population, we now need research that leads to a deeper understanding of the causes, consequences, and treatment of this common condition.

  View details for DOI 10.7326/0003-4819-147-5-200709040-00008

  View details for PubMedID 17785488

• Methylenetetrahydrofolate reductase C677T polymorphism and cognitive function in older women. American journal of epidemiology Elkins, J. S., Johnston, S. C., Ziv, E., Kado, D., Cauley, J. A., Yaffe, K. 2007; 166 (6): 672-8

  Abstract

  Homocysteine may play a causal role in cognitive decline. The authors analyzed the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotype, a correlate of plasma homocysteine levels, among 6,653 participants in the Study of Osteoporotic Fractures, a community-based, prospective cohort study of older women in four US states. During the years 1986-1998, the authors assessed whether the distribution of MTHFR C677T genotypes was independent of potential confounders and whether persons with the TT genotype had lower baseline performance or showed greater longitudinal declines on standard cognitive tests. Although ethnicity was associated with MTHFR genotype distribution within the entire cohort (p < 0.001), all measured confounders appeared independent of MTHFR genotype within the largest ethnically homogenous subgroup, persons of Northern and/or Central European ancestry (n = 5,668) (Kolmogorov-Smirnov p = 0.97). In this subgroup, the TT genotype was associated with lower scores on the Digit Symbol Substitution Test (p = 0.034) and the Trails B test (p = 0.020) and with a small excess annual decline on a modified version of the Mini-Mental State Examination (p = 0.035). Although the strength of the observed associations was modest, these results lend some support to the theory that an elevated homocysteine level contributes to cognitive decline.

  View details for DOI 10.1093/aje/kwm140

  View details for PubMedID 17638709

• Hyperkyphotic posture and risk of injurious falls in older persons: the Rancho Bernardo Study. The journals of gerontology. Series A, Biological sciences and medical sciences Kado, D. M., Huang, M. H., Nguyen, C. B., Barrett-Connor, E., Greendale, G. A. 2007; 62 (6): 652-7

  Abstract

  Falls among older adults can have serious physical and emotional consequences, ultimately leading to a loss of independence. Improved identification of those at risk for falls could lead to effective interventions. Because hyperkyphotic posture is associated with impaired physical functioning, we hypothesized that kyphosis may also be associated with falls.Participants were 1883 older adults from the Rancho Bernardo Study. Between 1988 and 1991, kyphosis was measured using a system of 1.7-cm blocks placed under the participants' heads if they were unable to lie flat without neck hyperextension. Data on falls including injurious falls, demographics, health, and habits were obtained from a self-administered questionnaire completed at the same visit.Hyperkyphosis was defined as requiring the use of > or = 1 blocks (n = 595, 31.6%). In this cohort, men were more likely to be hyperkyphotic than were women (p <.0001). Of those who fell, 36.3% were hyperkyphotic, versus 30.2% among those who did not fall (p =.015). Those who fell were older, more likely to be women, had lower body mass index, did not exercise, did not drink alcohol, and had poor self-reported physical and emotional health. In age- and sex-adjusted models, those with hyperkyphosis were at 1.38-fold increased odds of experiencing an injurious fall (95% confidence interval [CI], 1.05-1.91; p =.02) that increased to 1.48 using a cutoff of > or = 2 blocks versus < or = 1 blocks (95% CI, 1.10-2.00; p =.01). Although women were more likely to fall, after adjustment for possible confounders, men with moderate hyperkyphosis were at greatest fall risk.Moderate hyperkyphotic posture may signify an easily identifiable independent risk factor for injurious falls in older men, with the association being less pronounced in older women.

  View details for DOI 10.1093/gerona/62.6.652

  View details for PubMedID 17595423

• Lymphomatosis cerebri presenting as rapidly progressive dementia. The neurologist Weaver, J. D., Vinters, H. V., Koretz, B., Xiong, Z., Mischel, P., Kado, D. 2007; 13 (3): 150-3

  Abstract

  As the population ages, the incidence of dementing illness is increasing. Accurate and timely diagnosis provides the best hope for instituting appropriate treatment and educating the patient and family members as to prognosis based upon likely etiology in a given patient.We present a case of an elderly patient referred to our tertiary-care center for further evaluation of a rapidly progressive dementia, whose definitive diagnosis was delayed by nonspecific MRI findings, presence of 14-3-3 protein in the CSF, and nonspecific cutaneous lesions. At brain biopsy, he was thought to have a diffusely infiltrating lymphoma, with distinctive immunohistochemical features.This case is notable in that it presents a patient with progressive dementia whose diagnosis of primary central nervous system lymphoma (PCNSL) was delayed because of the lymphoma's atypical diffusely infiltrating nature. Awareness of this unique presentation may hasten the time between clinical presentation, diagnosis, and subsequent treatment.

  View details for DOI 10.1097/01.nrl.0000254706.85609.95

  View details for PubMedID 17495760

• Depressive symptoms as a predictor of cognitive decline: MacArthur Studies of Successful Aging. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Chodosh, J., Kado, D. M., Seeman, T. E., Karlamangla, A. S. 2007; 15 (5): 406-15

  Abstract

  The prevalence of dementia continues to rise, and yet, there are few known modifiable risk factors. Depression, as a treatable condition, may be important in the development of dementia. Our objective was to examine the association between depressive symptoms and longitudinal cognitive changes in older adults who were high-functioning at baseline.The authors analyzed data from a community-based cohort (aged 70-79 at baseline), who, at study entry, scored 7 or more (out of 9) on the Short Portable Mental Status Questionnaire (SPMSQ). Depressive symptoms were assessed at baseline using the depression subscale of the Hopkins Symptom Check List. Cognitive performance was measured at baseline and at seven-year follow up by the SPMSQ and by summary scores from standard tests of naming, construction, spatial recognition, abstraction, and delayed recall.After adjusting for potential confounders, including age, education, and chronic health conditions such as diabetes, heart attack, stroke, and hypertension, a higher number of baseline depressive symptoms were strongly associated with greater seven-year decline in cognitive performance and with higher odds of incident cognitive impairment, i.e., decline in SPMSQ score to < or = 6 (adjusted odds ratio per quartile of depressive symptoms score: 1.34, 95% confidence interval: 1.10-1.68).Depressive symptomatology independently predicts cognitive decline and incident cognitive impairment in previously high-functioning older persons.

  View details for DOI 10.1097/01.JGP.0b013e31802c0c63

  View details for PubMedID 17353297

• Sex steroid hormone gene polymorphisms and depressive symptoms in women at midlife. The American journal of medicine Kravitz, H. M., Janssen, I., Lotrich, F. E., Kado, D. M., Bromberger, J. T. 2006; 119 (9 Suppl 1): S87-93

  Abstract

  Single nucleotide polymorphism (SNP) genotype frequencies were examined to determine whether variation in 6 estrogen-related genes was associated with differences in self-reported depressive symptoms in women. In this substudy of the Study of Women's Health Across the Nation (SWAN), DNA from a multiracial/multiethnic sample of 1,538 African American, Caucasian, Chinese, and Japanese women aged 42 to 52 years participating in SWAN was genotyped. Depressive symptoms were measured with the Center for Epidemiologic Studies-Depression (CES-D) scale. After excluding data from women taking antidepressants (n=103), statistical models were fit using multivariate logistic regression to predict the association of estrogen-related polymorphisms with the dichotomized CES-D score. Among Caucasian women, those with the CYP1A1 rs2606345 CC and AC genotypes had approximately 2-fold greater odds of having depressive symptoms than did those with the AA genotype (95% confidence intervals [CIs], 1.33 to 4.66 and 1.25 to 3.14, respectively). African American women with the CC genotype of the same SNP had 10-fold greater odds of having more depressive symptoms than did women with the AA genotype (95% CI, 1.20 to 86.20). In Japanese women, the odds of depressive symptoms were nearly 5-fold higher among those with CYP 19 rs936306 TT genotype (95% CI, 1.10 to 22.17) than in women with the CC genotype and 9.6-fold higher (95% CI, 2.01 to 45.81) than in women with the CT genotype. The odds of depressive symptoms among Chinese women with the 17HSD rs615942 TT genotype were nearly 11-fold higher than in those with the GT genotype (95% CI, 1.94 to 60.84) and >7-fold higher than in those with the GG genotype (95% CI, 1.13 to 51.82). These data provide evidence that selected genes involved in estrogen synthesis and metabolism increase the odds of more depressive symptoms in women who are premenopausal or perimenopausal.

  View details for DOI 10.1016/j.amjmed.2006.07.010

  View details for PubMedID 16949393

• Hyperkyphotic posture and risk of future osteoporotic fractures: the Rancho Bernardo study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Huang, M. H., Barrett-Connor, E., Greendale, G. A., Kado, D. M. 2006; 21 (3): 419-23

  Abstract

  It is unknown whether kyphosis of the thoracic spine is an independent risk factor for future osteoporotic fractures. In 596 community-dwelling women, we found that with increasing kyphosis, there was a significant trend of increasing fracture risk that was independent of previous history of fractures or BMD.It is unknown whether kyphosis of the thoracic spine is an independent risk factor for future osteoporotic fractures.We conducted a prospective cohort study of 596 community-dwelling women, 47-92 years of age. Between 1988 and 1991, BMD of the hip and spine and kyphosis were measured. Kyphosis was measured by counting the number of 1.7-cm blocks necessary to place under the occiput so participants could lie flat without neck hyperextension. New fractures were reported over an average follow-up of 4 years.Using a cut-off of at least one block, 18% of the participants had hyperkyphotic posture (range, one to nine blocks). There were 107 women who reported at least one new fracture (hip, spine, wrist, clavicle, shoulder, arm, hand, rib, pelvis, leg, or ankle). In logistic regression analyses, older women with hyperkyphotic posture (defined as at least one block) had a 1.7-fold increased risk of having a future fracture independent of age, prior fracture, and spine or hip BMD (95% CI: 1.00-2.97; p = 0.049). There was a significant trend of increasing fracture risk with increasing number of blocks, with ORs ranging from 1.5 to 2.6 as the number of blocks increased from one to at least three blocks compared with those with zero blocks (trend p = 0.03; models adjusted for age, baseline fracture, spine or hip BMD). Stratification by baseline fracture status and controlling for other possible confounders or past year falls did not change the results.Whereas hyperkyphosis may often result from vertebral fractures, our study findings suggest that hyperkyphotic posture itself may be an important risk factor for future fractures, independent of low BMD or fracture history.

  View details for DOI 10.1359/JBMR.051201

  View details for PubMedID 16491290

  View details for PubMedCentralID PMC4964958

• Comparing a supine radiologic versus standing clinical measurement of kyphosis in older women: the Fracture Intervention Trial. Spine Kado, D. M., Christianson, L., Palermo, L., Smith-Bindman, R., Cummings, S. R., Greendale, G. A. 2006; 31 (4): 463-7

  Abstract

  A study of agreement between different measures of kyphosis, a clinical standing measure (Debrunner kyphometer; Protek AG, Bern, Switzerland) versus a supine radiologic measure (Cobb angle).To determine whether a supine radiologic measure of kyphosis in older women is a reasonable estimate of clinical kyphosis determined in the standing position, and to investigate a computerized assessment of the Cobb angle.Few studies have investigated kyphosis measurement agreement involving older adults.Using data from the Fracture Intervention Trial, we randomly selected 120 women, aged 55-80 years, who had a Debrunner kyphometer measure of kyphosis and supine lateral spine radiographs from which we measured the Cobb angle (either manually or by digitization). We calculated the intraclass correlation coefficient (ICC) from repeated measures analysis of variance to assess the agreement among the: (1) manual Cobb angle and Debrunner kyphometer, (2) digitized Cobb angle and Debrunner kyphometer, and (3) manual and digitized Cobb angle.The mean of both the manual and digitized Cobb angle was 45 degrees (range 18 degrees-83 degrees), and the mean Debrunner kyphometer reading was 48 degrees (range 17 degrees-83 degrees). The ICC between either of the 2 measures of the Cobb angle and Debrunner measurement was 0.68, indicating reasonable agreement. The ICC between the manual and digitized Cobb angle was 0.99, indicating excellent agreement.There is reasonable agreement between a supine radiologic and standing clinical measurement of kyphosis in older women.

  View details for DOI 10.1097/01.brs.0000200131.01313.a9

  View details for PubMedID 16481959

  View details for PubMedCentralID PMC4964957

• Hyperkyphotic posture and poor physical functional ability in older community-dwelling men and women: the Rancho Bernardo study. The journals of gerontology. Series A, Biological sciences and medical sciences Kado, D. M., Huang, M. H., Barrett-Connor, E., Greendale, G. A. 2005; 60 (5): 633-7

  Abstract

  Physical functional decline is often the determining factor that leads to loss of independence in older persons. Identifying risk factors for physical disability may lead to interventions that may prevent or delay the onset of functional decline. Our study objective was to determine the association between hyperkyphotic posture and physical functional limitations.Participants were 1578 older men and women from the Rancho Bernardo Study who had kyphotic posture measured as the distance from the occiput to table (units = 1.7-cm blocks, placed under the participant's head when lying supine on a radiology table). Self-reported difficulty in bending, walking, and climbing was assessed by standard questionnaires. Physical performance was assessed by measuring grip strength and ability to rise from a chair without the use of the arms.Men were more likely to be hyperkyphotic than were women (p <.0001). In multiply adjusted comparisons, there was a graded stepwise increase in difficulty in bending, walking and climbing, measured grip strength, and ability to rise from a chair. For example, the odds ratio (OR) of having to use the arms to stand up from a chair increased from 1.6 (95% confidence interval [CI]: 0.9-3.0) for individuals defined as hyperkyphotic by 1 block to 2.9 (95% CI: 1.7-5.1) for individuals defined as hyperkyphotic by 2 blocks to 3.7 (95% CI: 2.1-6.3) for individuals defined as hyperkyphotic by > or = 3 blocks compared to those who were not hyperkyphotic (p for trend < .0001).Older persons with hyperkyphotic posture are more likely to have physical functional difficulties.

  View details for DOI 10.1093/gerona/60.5.633

  View details for PubMedID 15972617

  View details for PubMedCentralID PMC1360196

• Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. The American journal of medicine Kado, D. M., Karlamangla, A. S., Huang, M. H., Troen, A., Rowe, J. W., Selhub, J., Seeman, T. E. 2005; 118 (2): 161-7

  Abstract

  Elevated plasma total homocysteine concentration may be a risk factor for cognitive decline and Alzheimer disease, but data from prospective studies are limited. Further, high homocysteine levels are associated with low vitamin status, and it is unknown whether it is homocysteine toxicity or vitamin insufficiency that is responsible for the observed cognitive dysfunction.We performed cross-sectional and longitudinal analyses of a cohort of 499 high-functioning community-dwelling persons aged 70 to 79 years to determine the effect of homocysteine and related vitamin plasma concentrations on cognitive function and cognitive decline. Nonfasting plasma concentrations of homocysteine, folate, vitamin B(6), and vitamin B(12) were measured at baseline. Summary measures of cognitive function were created from tests of multiple cognitive domains administered at baseline and again after 7 years.In cross-sectional analyses investigating each variable separately, subjects with elevated homocysteine levels, or low levels of folate or vitamin B(6), demonstrated worse baseline cognitive function. In longitudinal analyses, after adjusting for multiple covariates, including homocysteine, those in the bottom quartile of folate had a 1.6-fold increased risk (95% confidence interval: 1.01 to 2.31; P =0.04) of being in the worst quartile of 7-year cognitive decline. Low folate levels largely accounted for a trend towards greater cognitive decline with elevated homocysteine level.In high-functioning older adults, low folate levels appear to be a risk factor for cognitive decline. The risk of developing cognitive decline might be reduced through dietary folate intake.

  View details for DOI 10.1016/j.amjmed.2004.08.019

  View details for PubMedID 15694902

• Hyperkyphotic posture predicts mortality in older community-dwelling men and women: a prospective study. Journal of the American Geriatrics Society Kado, D. M., Huang, M. H., Karlamangla, A. S., Barrett-Connor, E., Greendale, G. A. 2004; 52 (10): 1662-7

  Abstract

  To determine the association between hyperkyphotic posture and rate of mortality and cause-specific mortality in older persons.Prospective cohort study.Rancho Bernardo, California.Subjects were 1,353 participants from the Rancho Bernardo Study who had measurements of kyphotic posture made at an osteoporosis visit between 1988 and 1991.Kyphotic posture was measured as the number of 1.7-cm blocks that needed to be placed under the participant's head to achieve a neutral head position when lying supine on a radiology table. Demographic and clinical characteristics and health behaviors were assessed at a clinic visit using standard questionnaires. Participants were followed for an average of 4.2 years, with mortality and cause of death confirmed using review of death certificates.Hyperkyphotic posture, defined as requiring one or more blocks under the occiput to achieve a neutral head position while lying supine, was more common in men than women (44% in men, 22% of women, P<.0001). In age- and sex-adjusted analyses, persons with hyperkyphotic posture had a 1.44 greater rate of mortality (95% confidence interval (CI)=1.12-1.86, P=.005). In multiply adjusted models, the increased rate of death associated with hyperkyphotic posture remained significant (relative hazard=1.40, 95% CI=1.08-1.81, P=.012). In cause-specific mortality analyses, hyperkyphotic posture was specifically associated with an increased rate of death due to atherosclerosis.Older men and women with hyperkyphotic posture have higher mortality rates.

  View details for DOI 10.1111/j.1532-5415.2004.52458.x

  View details for PubMedID 15450042

• A cure for all ills. Journal of the American Geriatrics Society Kado, D. M. 2004; 52 (8): 1399

  View details for DOI 10.1111/j.1532-5415.2004.52377.x

  View details for PubMedID 15271135

• Incident vertebral fractures and mortality in older women: a prospective study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA Kado, D. M., Duong, T., Stone, K. L., Ensrud, K. E., Nevitt, M. C., Greendale, G. A., Cummings, S. R. 2003; 14 (7): 589-94

  Abstract

  Older persons who have prevalent vertebral fractures have an increased risk of mortality. It is not known whether incident vertebral fractures are also associated with an increased risk of mortality. To determine whether older women with incident vertebral fractures have an increased risk of mortality, we conducted a prospective cohort study of 7233 community-dwelling older women aged 65 years or older who were enrolled in the Study of Osteoporotic Fractures. We measured incident vertebral fractures by radiographic morphometry of paired lateral spine X-rays taken an average of 3.7 years apart. We also collected information on baseline prevalent vertebral fractures; calcaneal bone density; anthropometric measures; and demographic, medical history, and lifestyle variables. Overall mortality was assessed and confirmed by receipt of death certificates. Over an average of 3.7 years, 389 (5.4%) women developed at least one incident vertebral fracture. During an additional 8 years of follow-up, 1617 (22%) women died. Women with at least one new fracture had an age-adjusted 32% increased risk of mortality (RH=1.32; 95% CI=1.10-1.58, P=0.003) compared to those without incident vertebral fractures. After adjustment for weight loss, physical frailty markers, and nine other predictors of mortality, there was no longer an independent association between incident vertebral fractures and mortality (RH=1.06; 95% CI=0.88 1.28). Older women with incident vertebral fractures have an increased risk of mortality that may be explained by weight loss and physical frailty.

  View details for DOI 10.1007/s00198-003-1412-5

  View details for PubMedID 12827222

• Homocysteine levels and decline in physical function: MacArthur Studies of Successful Aging. The American journal of medicine Kado, D. M., Bucur, A., Selhub, J., Rowe, J. W., Seeman, T. 2002; 113 (7): 537-42

  Abstract

  To test whether elevated homocysteine levels are associated with an increased risk of decline in physical function in older persons.We performed a prospective cohort study of 499 highly functioning men and women aged 70 to 79 years who were enrolled in the MacArthur Studies of Successful Aging. We measured total homocysteine levels and performance-based physical function at baseline; physical function measures were repeated an average of 28 months later. A summary measure of physical performance from tests of balance, gait, lower body strength and coordination, and manual dexterity was developed, and a change score was calculated as the difference in scores from 1988 to 1991.The mean (+/-SD) homocysteine level was 11.6 +/- 4.3 micromol/L. With each SD increase in homocysteine, there was an increased risk of being in the worst quartile of decline in physical function (odds ratio = 1.5; 95% confidence interval: 1.2 to 1.9) in analyses that adjusted for age, sex, baseline physical performance, smoking status, vitamin B(12) levels, and incident stroke. Similar results were seen when change in physical performance was treated as a continuous variable.Older persons with elevated plasma homocysteine levels are at an increased risk of decline in physical function.

  View details for DOI 10.1016/s0002-9343(02)01269-x

  View details for PubMedID 12459398

• Rapid resting heart rate: a simple and powerful predictor of osteoporotic fractures and mortality in older women. Journal of the American Geriatrics Society Kado, D. M., Lui, L. L., Cummings, S. R. 2002; 50 (3): 455-60

  Abstract

  To determine whether resting heart rate is associated with several types of osteoporotic fractures, mortality, and cause-specific mortality in older women.A prospective cohort study.Four communities across the United States.We prospectively assessed resting pulse rate in 9,702 women aged 65 and older enrolled in the Study of Osteoporotic Fractures.Resting pulse was measured in the supine position. Hip, humerus, pelvis, rib, ankle, and wrist fractures were identified by self-report and validated by radiographs. Incident vertebral fractures were assessed by quantitative morphometry. Cause-specific mortality was assessed from death certificates and hospital discharge summaries.Women with resting heart rates of greater than 80 beats per minute (bpm) (n = 1,140 (12%)) had an adjusted 1.6-fold (95% confidence interval (CI) = 1.2-2.0) increased risk of either a hip, pelvis, or rib fracture and a 1.9-fold (95% CI = 1.4-2.5) increased risk of vertebral fracture. A heart rate of 80 bpm or greater was also associated with 1.4-fold (95% Cl = 1.2-1.5) increased all-cause mortality and 1.5-fold (95% CI = 1.2-2.1) increased coronary heart disease mortality. Investigating resting heart rate as a continuous variable, we detected a general pattern of increasing risks with higher heart rate that could not be explained by age, weight, poor health, physical activity, hyperthyroidism, or smoking.Older women with resting heart rates of 80 bpm or more have an increased risk of several osteoporotic fractures and of mortality that is not explained by other risk factors. Heart rate may be a simple tool for assessing risk of fracture and of death from coronary heart disease in older women.

  View details for DOI 10.1046/j.1532-5415.2002.50110.x

  View details for PubMedID 11943040

• Prevalent vertebral deformities predict mortality and hospitalization in older women with low bone mass. Fracture Intervention Trial Research Group. Journal of the American Geriatrics Society Ensrud, K. E., Thompson, D. E., Cauley, J. A., Nevitt, M. C., Kado, D. M., Hochberg, M. C., Santora, A. C., Black, D. M. 2000; 48 (3): 241-9

  Abstract

  To determine the relationship between prevalent vertebral deformities and the risk of mortality and hospitalization in older women with low bone mass.A prospective cohort study.Eleven clinical centers in the United States.A total of 6459 community-dwelling women with low bone mass aged 55 to 81 participated in the Fracture Intervention Trial (FIT), a multicenter clinical trial of alendronate that enrolled women into one of two study arms based solely on the presence or absence of existing radiographic vertebral deformities. There were 2027 women with at least one vertebral deformity enrolled in the vertebral fracture arm of FIT and followed prospectively for an average of 2.9 years, whereas 4432 women with no vertebral deformity were enrolled in the clinical fracture arm of FIT and followed prospectively for an average of 4.2 years.Determination of prevalent vertebral deformities on baseline lateral thoracic and lumbar spine radiographs was made at the coordinating center using a combination of radiographic morphometry by digitization and semiquantitative radiologic interpretation. Deaths were confirmed by obtaining copies of original death certificates of all participants who died. Episodes of hospitalization were captured through adverse event reporting; hospitalizations resulting solely from adverse events containing the words "fracture" or "trauma" were excluded from the analyses.During the follow-up period, 122 women died, and 1676 women were hospitalized on at least one occasion for reasons not related solely to fracture. Compared with women without prevalent vertebral deformities, those women with prevalent deformities had higher risks of mortality (age- and treatment assignment-adjusted relative risk 1.60, 95% confidence interval (CI), 1.10-2.32) and hospitalization (age- and treatment assignment-adjusted relative risk 1.18, 95% CI, 1.06-1.31). In addition, further adjustment for other factors, including smoking status, physical activity, hypertension, coronary heart disease, obstructive lung disease, any fracture since the age of 50, health status, total hip BMD, and body mass index did not alter the association between prevalent vertebral deformities and risk of mortality substantially (multivariate relative risk 1.49, 95% CI, 1.05-2.21). Adjustment for all these factors and diabetes also did not change the relationship between prevalent vertebral deformities and hospitalization (multivariate relative risk 1.14, 95% CI, 1.02-1.27). Rates of mortality and hospitalization increased with increasing number of prevalent vertebral deformities (tests for trend P < .01).Prevalent vertebral deformities in older women with low bone mass are associated with increased risks of mortality and hospitalization. Only a portion of this increased risk was explained by other known predictors of these outcomes.

  View details for DOI 10.1111/j.1532-5415.2000.tb02641.x

  View details for PubMedID 10733048

• Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Archives of internal medicine Kado, D. M., Browner, W. S., Palermo, L., Nevitt, M. C., Genant, H. K., Cummings, S. R. 1999; 159 (11): 1215-20

  Abstract

  Osteoporotic fractures, including clinically detected vertebral fractures, are associated with increased mortality. However, only one third of vertebral fractures are diagnosed. It is unknown whether vertebral fractures, whether clinically apparent or not, are associated with greater mortality.To test the hypothesis that women with prevalent vertebral fractures have greater mortality than those without fractures and to describe causes of death associated with vertebral fractures.Prospective cohort study with mean follow-up of 8.3 years.Four clinical centers in the United States.A total of 9575 women aged 65 years or older and enrolled in the Study of Osteoporotic Fractures.Vertebral fractures by radiographic morphometry; calcaneal bone mineral density; demographic, medical history, and lifestyle variables; blood pressure; and anthropometric measures. In a subset of 606 participants, thoracic curvature was measured during a second clinic visit.Hazard ratios for mortality and cause-specific mortality.At baseline, 1915 women (20.0%) were diagnosed as having vertebral fractures. Compared with women who did not have a vertebral fracture, women with 1 or more fractures had a 1.23-fold greater age-adjusted mortality rate (95% confidence interval, 1.10-1.37). Mortality rose with greater numbers of vertebral fractures, from 19 per 1000 woman-years in women with no fractures to 44 per 1000 woman-years in those with 5 or more fractures (P for trend, <.001). In particular, vertebral fractures were related to the risk of subsequent cancer (hazard ratio, 1.4;95% confidence interval, 1.1-1.7) and pulmonary death (hazard ratio, 2.1;95% confidence interval, 1.4-3.0). In the subset of women who underwent thoracic curvature measurements, severe kyphosis was also related to pulmonary deaths (hazard ratio, 2.6;95% confidence interval, 1.3-5.1).Women with radiographic evidence of vertebral fractures have an increased mortality rate, particularly from pulmonary disease and cancer.

  View details for DOI 10.1001/archinte.159.11.1215

  View details for PubMedID 10371229

• Clinical characterization of thrombotic microangiopathy in HIV infection. AIDS (London, England) Kado, D. M., Korotzer, B. S., Brass, E. P. 1996; 10 (14): 1747-9

  View details for DOI 10.1097/00002030-199612000-00028

  View details for PubMedID 8970704