- Endocrinology/Diabetes, Pediatric
Honors & Awards
Member, Alpha Omega Alpha (1976)
Member, Phi Beta Kappa (1970)
Boards, Advisory Committees, Professional Organizations
Member, Endocrine Society (1999 - Present)
Member, American Society of Bone and Mineral Research (1999 - Present)
Member, American Academy of Pediatrics (2000 - Present)
member, Pediatric Endocrine Society (2000 - Present)
Board Certification: Pediatrics, American Board of Pediatrics (1981)
Internship:UCSF Medical Center (1977) CA
Medical Education:Tufts University (1976) MA
Residency:UCSF Medical Center (1978) CA
Fellowship:Hospital for Sick Children (1982) Canada
Residency:Stanford University Medical Center (1979) CA
BA, Harvard University, Social Science (1970)
MD, Tufts School of Medicine (1976)
Current Research and Scholarly Interests
Prevention of osteoporosis begins in childhood and adolescence by optimizing acquistion of bone mineral during the critical adolescent years. Body mass, calcium nutriture, physical activity, growth and sex steroid hormones, and genetic factors are all thought to be important determinants of bone mass although the relative contribution of each remains controversial. My research interests are directed at the process of bone mineral acquisition during childhood in healthy young people and patients with disorders that place them at risk for premature osteoporosis. I am also exploring the optimal therapies for children with bone fragility. Finally, I have been comparing the value of newer non-invasive methods for assessing bone fragility in the pediatric population.
Effect of Vitamin D Supplementation on Inflammation and Cardiometabolic Risk Factors in Obese Adolescents
Large studies of children show that over half of the children in the United States of America do not have enough vitamin D stored in their bodies. In children who are overweight or obese, the percentage of children who do not have enough vitamin D is even higher. Vitamin D is essential for the body to maintain normal calcium levels and strong bones. Recent research shows that through the actions of inflammatory markers, levels in the blood that measure inflammation in the body, vitamin D plays many other important roles in the body like helping to regulate the immune system, blood sugar levels, blood pressure, and body fat. The purpose of this study is to determine the effect of vitamin D supplementation on inflammatory markers in obese and overweight adolescents. As a secondary goal, we would like to evaluate cardiometabolic risk factors and the correlation between body mass index, vitamin D stores and inflammatory cytokines. In an observed, randomized controlled trial over 6 months we will provide observed vitamin D supplementation or placebo to healthy obese and overweight adolescents and measure changes in inflammatory markers, lipids, blood pressure, and mean blood sugars. We hypothesize that administration of vitamin D to these patients will improve their inflammatory profile and cardiometabolic risk factors (blood glucose, blood pressure, and lipid profile).
Stanford is currently not accepting patients for this trial. For more information, please contact Sejal Shah, (650) 723 - 5791.
- Independent Studies (5)
A Case Report of Hypoglycemia and Hypogammaglobulinemia: DAVID syndrome in a patient with a novel NFKB2 mutation.
journal of clinical endocrinology and metabolism
DAVID syndrome (Deficient Anterior pituitary with Variable Immune Deficiency) is a rare disorder in which children present with symptomatic ACTH deficiency preceded by hypogammaglobulinemia from B-cell dysfunction with recurrent infections, termed common variable immunodeficiency (CVID). Subsequent whole exome sequencing studies have revealed germline heterozygous C-terminal mutations of NFKB2 as either a cause of DAVID syndrome or of CVID without clinical hypopituitarism. However, to the best of our knowledge there have been no cases in which the endocrinopathy has presented in the absence of a prior clinical history of CVID.A previously healthy 7 year-old boy with no history of clinical immunodeficiency, presented with profound hypoglycemia and seizures. He was found to have secondary adrenal insufficiency and was started on glucocorticoid replacement. An evaluation for autoimmune disease, including for anti-pituitary antibodies, was negative. Evaluation unexpectedly revealed hypogammaglobulinemia (decreased IgG, IgM, and IgA). He had moderately reduced serotype-specific IgG responses following pneumococcal polysaccharide vaccine. Subsequently, he was found to have growth hormone (GH) deficiency. Six years after initial presentation, whole exome sequencing revealed a novel de novo heterozygous NFKB2 missense mutation c.2596A>C (p.Ser866Arg) in the C-terminal region predicted to abrogate the processing of the p100 NFKB2 protein to its active p52 form.Isolated early-onset ACTH deficiency is rare and C-terminal region NFKB2 mutations should be considered as an etiology even in the absence of a clinical history of CVID. Early immunologic evaluation is indicated in the diagnosis and management of isolated ACTH deficiency.
View details for DOI 10.1210/jc.2017-00341
View details for PubMedID 28472507
- Tumor-induced Osteomalacia in a 3-Year-Old With Unresectable Central Giant Cell Lesions JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY 2017; 39 (1): E21-E24
Controlled Pilot Study of High-Impact Low-Frequency Exercise on Bone Loss and Vital-Sign Stabilization in Adolescents With Eating Disorders.
journal of adolescent health
2017; 60 (1): 33-37
Adolescents with anorexia nervosa (AN) face an increased lifetime risk of bone fragility. This randomized controlled study examined the efficacy and safety of a high-impact activity program on markers of bone turnover and stabilization of vital signs (VSS).Forty-one hospitalized adolescents with AN were randomly assigned to routine care or routine care plus 20 jumps twice daily. Bone markers were measured at baseline days 1-3 (T1), days 4-6 (T2), and days 7-9 (T3). The primary outcome was change in bone-specific alkaline phosphatase (BSAP) at T3 adjusted for BSAP and % median body mass index at T1. Secondary outcomes were serum N-telopeptide (NTX) and osteocalcin at T3. Safety was determined by comparing weight gain, time to VSS and length of stay for each group.BSAP, NTX, or osteocalcin did not differ between groups at baseline or at T3. BSAP and NTX at T3 were not associated with group of enrollment or % median body mass index. VSS was significantly reduced in the intervention group compared with the control group (11.6 ± 5.7 days vs. 17 ± 10.5 days, p = .049). There was no significant difference in weight gain or length of stay between groups.Twice-daily jumping activity failed to influence markers of bone turnover in adolescents with AN but was well tolerated, shortened time to vital-sign stabilization and did not slow weight gain.
View details for DOI 10.1016/j.jadohealth.2016.08.028
View details for PubMedID 27836532
Tumor-induced Osteomalacia in a 3-Year-Old With Unresectable Central Giant Cell Lesions.
Journal of pediatric hematology/oncology
Tumor-induced osteomalacia (TIO) is a rare cause of hypophosphatemia involving overproduction of fibroblast growth factor 23. TIO has been described largely in adults with small mesenchymal tumors. We report a case of TIO in a child who presented with knee pain and radiographic findings concerning for rickets, and was found to have maxillomandibular giant cell lesions. The patient was treated with oral phosphorus and calcitriol, surgical debulking, and intralesional corticosteroids, which resulted in tumor regression and normalization of serum fibroblast growth factor 23and phosphorus. This case illustrates the occurrence of this rare paraneoplastic syndrome in children and adds to our knowledge about clinical manifestations and pathologic findings associated with pediatric TIO.
View details for PubMedID 27820122
- The Determinants of Peak Bone Mass. journal of pediatrics 2016
A Multifaceted Mentoring Program for Junior Faculty in Academic Pediatrics
TEACHING AND LEARNING IN MEDICINE
2016; 28 (3): 320-328
The departure of physician-scientists from education and research into clinical practice is a growing challenge for the future of academic medicine. Junior faculty face competing demands for clinical productivity, teaching, research, and work-life integration, which can undermine confidence in the value of an academic career. Mentorship is important to foster career development and satisfaction in junior faculty.The goals of this academic pediatrics department were to develop, implement, and evaluate a multifaceted pediatric mentoring program to promote retention and satisfaction of junior faculty. Program elements included one-on-one mentor-mentee meetings, didactic workshops, grant review assistance, and facilitated peer-group mentoring. Program effectiveness was assessed using annual surveys of mentees and structured mentee exit interviews, as well as retention data for assistant professors.The mentees were instructors and assistant professors in the department of pediatrics.Seventy-nine mentees participated in the program from 2007 through 2014. The response rate from seven annual surveys was 84%. Sixty-nine percent of mentees felt more prepared to advance their careers, 81% had a better understanding of the criteria for advancement, 84% were satisfied with the program, and 95% found mentors accessible. Mentees who exited the program reported they most valued the one-on-one mentoring and viewed the experience positively regardless of promotion. Retention of assistant professors improved after initiation of the program; four of 13 hired from 2002 to 2006 left the institution, whereas 18 of 18 hired from 2007 to 2014 were retained.This multifaceted mentoring program appeared to bolster satisfaction and enhance retention of junior pediatric faculty. Mentees reported increased understanding of the criteria for promotion and viewed the program as a positive experience regardless of career path. Individual mentor-mentee meetings were needed at least twice yearly to establish the mentoring relationship. Identifying "next steps" at the end of individual meetings was helpful to hold both parties accountable for progress. Mentees most valued workshops fostering development of tangible skills (such as scientific writing) and those clarifying the criteria for promotion more transparent. Facilitated peer-group mentoring for mentees at the instructor rank provided valuable peer support.
View details for DOI 10.1080/10401334.2016.1153476
View details for Web of Science ID 000379862600011
View details for PubMedID 27054562
Large Doses of Vitamin D Fail to Increase 25-Hydroxyvitamin D Levels or to Alter Cardiovascular Risk Factors in Obese Adolescents: A Pilot Study.
journal of adolescent health
2015; 57 (1): 19-23
Vitamin D deficiency and cardiometabolic risk factors are common in obese adolescents. Observational studies demonstrate an inverse relationship among serum 25-hydroxyvitamin D (25OHD) and obesity, insulin resistance, and inflammatory cytokines. This pilot study explores if vitamin D supplementation could reduce serum concentrations of inflammatory cytokines (interleukin [IL] 6, IL-10, tumor necrosis factor α), adiponectin, lipids, hemoglobin A1C, and high-sensitivity C-reactive protein (hs-CRP). A secondary aim was to determine the associations between baseline serum 25OHD concentrations and body mass index (BMI), hs-CRP, inflammatory cytokines, and lipids.Overweight and obese adolescents enrolled in this 24-week, randomized, double-blind study were given 150,000 IU ergocalciferol or placebo at baseline and 12 weeks. Outcome measurements included serum 25OHD, inflammatory cytokines, adiponectin, hs-CRP, lipids, hemoglobin A1C, and BMI at baseline, 12, and 24 weeks.Of 40 participants, 31 (78%) completed the study. Mean ± standard error 25OHD levels were similar in vitamin D and placebo groups at baseline (19.6 ± 5.3 vs. 25.8 ± 10.8 ng/mL) and 24 weeks (20.1 ± 3.4 vs. 24.6 ± 8.4 ng/mL). Inflammatory and cardiovascular markers were not significantly different between groups at 24 weeks. Serum 25OHD at baseline was associated with BMI (r = -.44 [95% confidence interval, -.66 to -.15]) but not with other outcome measures.Supplementation with vitamin D at 150,000 IU every 3 months failed to increase serum 25OHD or alter inflammatory markers and lipids in overweight and obese youth. Further studies are needed to establish the dose of vitamin D required to increase 25OHD and determine potential effects on metabolic risk factors in obese teens.
View details for DOI 10.1016/j.jadohealth.2015.02.006
View details for PubMedID 25873553
Primary ovarian insufficiency in adolescents: a case series.
International journal of pediatric endocrinology
2015; 2015 (1): 13-?
Primary ovarian insufficiency (POI) is characterized by 4 to 6 months of amenorrhea and elevated serum FSH and LH in females less than 40 years. Ovarian insufficiency is uncommon in pediatrics and typically results from a chromosomal abnormality or treatment for malignancy. Idiopathic POI in which no apparent precipitant is identified is even rarer. After encountering three teens with idiopathic POI in recent months, we utilized an informatics-enabled search of the electronic medical records from our hospital to identify all cases of idiopathic POI presenting from 1998-2013.15 girls (ages 14.4 to 17.9 years) met criteria for idiopathic POI. At diagnosis, breast development ranged from Tanner stage 1 to 5; 6 of 15 patients had secondary amenorrhea. All patients presented in the past 11 years and 13 of 15 in the past 5 years.In this first case series of POI from the United States, we observed a clustering at our institution in recent years. If an increased incidence of idiopathic POI is identified at other institutions, further investigation into potential environmental and genetic precipitants is warranted.
View details for DOI 10.1186/s13633-015-0009-z
View details for PubMedID 25983758
Diagnosis and treatment of pediatric osteoporosis
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
2014; 21 (6): 454-460
Progress toward identifying and treating disorders of bone fragility in pediatric patients has been considerable in recent years. This article will summarize several key advances in the management of osteoporosis in children and adolescents.Recommendations from the 2013 pediatric Position Development Conference provide expert guidance for evaluating bone health in younger patients. The diagnosis of pediatric osteoporosis can be made in a child with low-trauma vertebral fractures or a combination of low bone mass and long bone fractures. Management of bone fragility includes optimizing nutrition, activity, and treatment of the underlying disease. Pharmacologic agents can be considered if these measures fail to prevent further bone loss or fractures. Although the efficacy and safety of several intravenous and oral bisphosphonates have been examined, there is still no consensus on the optimal drug, dose, or duration of treatment. Observational studies of children with secondary osteoporosis provide insight into risk factors for fracture or the potential for recovery.Despite advances in the diagnosis and treatment of pediatric osteoporosis, more research is needed. Randomized controlled trials of pharmacologic agents should be defined to target those identified at the highest risk by observational studies.http://links.lww.com/COE/A9
View details for DOI 10.1097/MED.0000000000000106
View details for Web of Science ID 000344799000004
View details for PubMedID 25232753
Dual-Energy X-Ray Absorptiometry Interpretation and Reporting in Children and Adolescents: The Revised 2013 ISCD Pediatric Official Positions
JOURNAL OF CLINICAL DENSITOMETRY
2014; 17 (2): 225-242
The International Society for Clinical Densitometry Official Revised Positions on reporting of densitometry results in children represent current expert recommendations to assist health care providers determine which skeletal sites should be measured, which, if any, adjustments should be made, reference databases to be used, and the elements to include in a dual-energy X-ray absorptiometry report. The recommended scanning sites remain the total body less head and the posterior-anterior spine. Other sites such as the proximal femur, lateral distal femur, lateral vertebral assessment, and forearm are discussed but are only recommended for specific pediatric populations. Different methods of interpreting bone density scans in children with short stature or growth delay are presented. The use of bone mineral apparent density and height-adjusted Z-scores are recommended as suitable size adjustment techniques. The validity of appropriate reference databases and technical considerations to consider when upgrading software and hardware remain unchanged. Updated reference data sets for all contemporary bone densitometers are listed. The inclusion of relevant demographic and health information, technical details of the scan, Z-scores, and the wording "low bone mass or bone density" for Z-scores less than or equal to -2.0 standard deviation are still recommended for clinical practice. The rationale and evidence for the development of the Official Positions are provided. Changes in the grading of quality of evidence, strength of recommendation, and worldwide applicability represent a change in current evidence and/or differences in opinion of the expert panelists used to validate the position statements for the 2013 Position Development Conference.
View details for DOI 10.1016/j.jocd.2014.01.003
View details for Web of Science ID 000335933500002
View details for PubMedID 24690232
- Burnout in pediatric residents over a 2-year period: a longitudinal study. Academic pediatrics 2014; 14 (2): 167-172
- Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions. International Society for Clinical Densitometry.J Clin Densitom. 2014;17:225-42. Journal of Clinical Densitometry 2014; 17: 225-242
Cost-effectiveness of Universal Serologic Screening to Prevent Nontraumatic Hip and Vertebral Fractures in Patients With Celiac Disease.
Clinical gastroenterology and hepatology
2013; 11 (6): 645-653
Patients with asymptomatic or poorly managed celiac disease can experience bone loss, placing them at risk for hip and vertebral fractures. We analyzed the cost-effectiveness of universal serologic screening (USS) vs symptomatic at-risk screening (SAS) strategies for celiac disease because of the risk of nontraumatic hip and vertebral fractures if untreated or undiagnosed.We developed a lifetime Markov model of the screening strategies, each with male or female cohorts of 1000 patients who were 12 years old when screening began. We screened serum samples for levels of immunoglobulin A, compared with tissue transglutaminase and total immunoglobulin A, and findings were confirmed by mucosal biopsy. Transition probabilities and quality of life estimates were obtained from the literature. We used generalizable cost estimates and Medicare reimbursement rates and ran deterministic and probabilistic sensitivity analyses.For men, the average lifetime costs were $8532 and $8472 for USS and SAS strategies, respectively, corresponding to average quality-adjusted life year gains of 25.511 and 25.515. Similarly for women, costs were $11,383 and $11,328 for USS and SAS strategies, respectively, corresponding to quality-adjusted life year gains of 25.74 and 25.75. Compared with the current standard of care (SAS), USS produced higher average lifetime costs and lower quality of life for each sex. Deterministic and probabilistic sensitivity analyses showed that the model was robust to realistic changes in all the variables, making USS cost-ineffective on the basis of these outcomes.USS and SAS are similar in lifetime costs and quality of life, although the current SAS strategy was overall more cost-effective in preventing bone loss and fractures among patients with undiagnosed or subclinical disease. On the basis of best available supportive evidence, it is more cost-effective to maintain the standard celiac screening practices, although future robust population-based evidence in other health outcomes could be leveraged to reevaluate current screening guidelines.
View details for DOI 10.1016/j.cgh.2012.12.037
View details for PubMedID 23357490
Correlates of low bone mass in children with generalized forms of epidermolysis bullosa
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
2011; 65 (5): 1001-1009
Epidermolysis bullosa (EB) is a family of rare, heterogeneous, genetic disorders characterized by fragility of the skin and mucous membranes. Reduced bone mass and fractures have been recognized as complications of generalized forms of EB.We sought to describe the range and to estimate the prevalence of low bone mass in children with generalized EB, and to identify correlates of low bone mass in this population.This was a prospective, observational study of 24 patients with generalized EB. Each patient completed a history, physical examination, laboratory studies, bone age, and x-rays of the lumbar spine. Those aged 6 years and older underwent dual energy x-ray absorptiometry scans of the lumbar spine. Primary outcomes were areal bone mineral density (aBMD) based on chronologic age, bone age, and adjusted for height Z-score. Descriptive statistics were used to summarize results, and linear regression was used to determine factors associated with low aBMD.Mean lumbar spine aBMD Z-scores ± SD were: -2.6 ± 1.4 for chronologic age, -1.7 ± 1.3 for bone age, and -1.0 ± 1.2 after adjusting for height Z-score. aBMD Z-scores were less than or equal to -2 in 64% for chronologic age, 50% for bone age, and 28% after adjusting for height Z-score. aBMD correlated with height Z-score, weight Z-score, extensive blistering, immobility, albumin, hemoglobin, iron, erythrocyte sedimentation rate, and c-reactive protein values.Small sample size was a limitation.Children with severe, generalized recessive dystrophic EB have low aBMD for age. Deficits in aBMD were reduced after adjusting for delayed skeletal maturation and small body size.
View details for DOI 10.1016/j.jaad.2010.08.028
View details for Web of Science ID 000296268000011
View details for PubMedID 21550693
Patterns of bone mineral acquisition in children with epidermolysis bullosa: a longitudinal study
BRITISH JOURNAL OF DERMATOLOGY
2011; 165 (5): 1081-1086
Reduced bone mass and fractures are known complications of generalized forms of epidermolysis bullosa (EB). However, the aetiology - inadequate bone acquisition, premature bone loss, or a combination - is unclear.To determine patterns of bone mineral acquisition in children with EB and to identify clinical and laboratory correlates of change in areal bone mineral density (aBMD).Seventeen subjects ≥ 6 years of age with generalized EB were studied at two visits at least 12 months apart with clinical and laboratory evaluations and dual energy X-ray absorptiometry scans of the lumbar spine. Wilcoxon signed-rank tests were used to determine if changes from baseline to follow-up were significant. Wilcoxon rank-sum tests were used to compare subjects with gains in aBMD Z-score with those who experienced no change or decreases to determine if baseline laboratory or clinical characteristics differed between the two groups.Subjects gained height and weight at follow-up, but there was no significant improvement in mean Z-scores for height, weight or body mass index. Laboratory values did not change significantly. Mean bone mineral content and aBMD of the lumbar spine increased significantly at follow-up, but mean aBMD Z-scores remained static. No differences in clinical characteristics or laboratory values were seen between subjects with increased aBMD Z-scores vs. those whose scores decreased or did not change.Low bone mass in children with generalized EB is due primarily to inadequate gains in aBMD. Interventions to improve overall health and to help build bone mass in this patient population are warranted.
View details for DOI 10.1111/j.1365-2133.2011.10517.x
View details for Web of Science ID 000297318700024
View details for PubMedID 21729034
Characterization of low bone mass in young patients with thalassemia by DXA, pQCT and markers of bone turnover
2011; 48 (6): 1305-1312
Previous reports using dual x-ray absorptiometry (DXA) suggest that up to 70% of adults with thalassemia major (Thal) have low bone mass. However, few studies have controlled for body size and pubertal delay, variables known to affect bone mass in this population. In this study, bone mineral content and areal density (BMC, aBMD) of the spine and whole body were assessed by DXA, and volumetric BMD and cortical geometries of the distal tibia by peripheral quantitative computed tomography (pQCT) in subjects with Thal (n = 25, 11 male, 10 to 30 years) and local controls (n=34, 15 male, 7 to 30 years). Z-scores for bone outcomes were calculated from reference data from a large sample of healthy children and young adults. Fasting blood and urine were collected, pubertal status determined by self-assessment and dietary intake and physical activity assessed by written questionnaires. Subjects with Thal were similar in age, but had lower height, weight and lean mass index Z-scores (all p < 0.001) compared to controls. DXA aBMD was significantly lower in Thal compared to controls at all sites. Adult Thal subjects (> 18 years, n = 11) had lower tibial trabecular vBMD (p = 0.03), cortical area, cortical BMC, cortical thickness, periosteal circumference and section modulus Z-scores (all p < 0.01) compared to controls. Cortical area, cortical BMC, cortical thickness, and periosteal circumference Z-scores (p = 0.02) were significantly lower in young Thal (≤ 18 years, n = 14) compared to controls. In separate multivariate models, tibial cortical area, BMC, and thickness and spine aBMD and whole body BMC Z-scores remained lower in Thal compared to controls after adjustment for gender, lean mass and/or growth deficits (all p < 0.01). Tanner stage was not predictive in these models. Osteocalcin, a marker of bone formation, was significantly reduced in Thal compared to controls after adjusting for age, puberty and whole body BMC (p=0.029). In summary, we have found evidence of skeletal deficits that cannot be dismissed as an artifact of small bone size or delayed maturity alone. Given that reduced bone density and strength are associated with increased risk of fracture, therapies focused on increasing bone formation and bone size in younger patients are worthy of further evaluation.
View details for DOI 10.1016/j.bone.2011.03.765
View details for Web of Science ID 000290974200012
View details for PubMedID 21443975
View details for PubMedCentralID PMC3095710
Bone mineral acquisition is meager in children with epidermolysis bullosa
71st Annual Meeting of the Society-for-Investigative-Dermatology
NATURE PUBLISHING GROUP. 2011: S66–S66
View details for Web of Science ID 000289035600393
Biopsychosocial variables associated with substantial bone mineral density loss during the use of depot medroxyprogesterone acetate in adolescents adolescents who lost 5% or more from baseline vs those who lost less than 5%
2010; 82 (6): 503-512
It is unclear why some adolescents experience substantial bone mineral density (BMD) loss, while others experience a minimal decrease during depot medroxyprogesterone acetate (DMPA) use. We examined biopsychosocial factors in adolescents who experienced ≥5% BMD loss from baseline compared with adolescents who experienced <5% BMD loss during DMPA use.A multicenter, prospective, nonrandomized study of 181 female adolescents who initiated DMPA for contraception was conducted. BMD (by dual-energy X-ray absorptiometry) and serum estradiol were measured at initiation and every 6 months for 240 weeks of DMPA use.Half of participants experienced BMD loss of ≥5% from baseline at the hip, and a quarter experienced BMD loss of ≥5% at the lumbar spine (BMD substantial losers, SL). Hip and lumbar spine BMD-SL received a significantly greater number of DMPA injections than non-SL (p<.001). Decreased estradiol levels did not statistically differ between BMD loss subgroups. Hip BMD-SL had significantly lower baseline body mass index (BMI) than non-SL (p=.002), and there was an inverse relationship between weight gain and degree of BMD loss. Mean calcium intake was significantly lower (p<.05) in hip BMD-SL, and reported alcohol use was significantly higher (p<.05) in lumbar spine BMD-SL compared with non-SL.BMD loss of ≥5% was more common at the hip than at the lumbar spine among adolescents using DMPA. Decreased serum estradiol levels did not correlate with magnitude of BMD loss. Lower BMI and calcium intake and greater alcohol use were associated with greater BMD loss in adolescents using DMPA.
View details for DOI 10.1016/j.contraception.2010.04.022
View details for Web of Science ID 000284671100006
View details for PubMedID 21074012
Nutritional factors that influence change in bone density and stress fracture risk among young female cross-country runners.
PM & R : the journal of injury, function, and rehabilitation
2010; 2 (8): 740-750
To identify nutrients, foods, and dietary patterns associated with stress fracture risk and changes in bone density among young female distance runners.Two-year, prospective cohort study. Observational data were collected in the course of a multicenter randomized trial of the effect of oral contraceptives on bone health.One hundred and twenty-five female competitive distance runners ages 18-26 years.Dietary variables were assessed with a food frequency questionnaire.Bone mineral density and content (BMD/BMC) of the spine, hip, and total body were measured annually by dual x-ray absorptiometry (DEXA). Stress fractures were recorded on monthly calendars, and had to be confirmed by radiograph, bone scan, or magnetic resonance imaging.Seventeen participants had at least one stress fracture during follow-up. Higher intakes of calcium, skim milk, and dairy products were associated with lower rates of stress fracture. Each additional cup of skim milk consumed per day was associated with a 62% reduction in stress fracture incidence (P < .05); and a dietary pattern of high dairy and low fat intake was associated with a 68% reduction (P < .05). Higher intakes of skim milk, dairy foods, calcium, animal protein, and potassium were associated with significant (P < .05) gains in whole-body BMD and BMC. Higher intakes of calcium, vitamin D, skim milk, dairy foods, potassium, and a dietary pattern of high dairy and low fat were associated with significant gains in hip BMD.In young female runners, low-fat dairy products and the major nutrients in milk (calcium, vitamin D, and protein) were associated with greater bone gains and a lower stress fracture rate. Potassium intake was also associated with greater gains in hip and whole-body BMD.
View details for DOI 10.1016/j.pmrj.2010.04.020
View details for PubMedID 20709302
- Nutritional Factors That Influence Change in Bone Density and Stress Fracture Risk Among Young Female Cross-Country Runners PM&R 2010; 2 (8): 740-750
Inadequate Vitamin D Status in Adolescents with Substantial Bone Mineral Density Loss During the Use of Depot Medroxyprogesterone Acetate Injectable Contraceptive: A Pilot Study
JOURNAL OF PEDIATRIC AND ADOLESCENT GYNECOLOGY
2010; 23 (4): 209-214
To examine vitamin D and parathormone (PTH) levels in adolescents who experienced substantial bone mineral density (BMD) loss during depot medroxyprogesterone acetate (DMPA) use.A non-randomized, multi-center study, during which DMPA was administered every 12 weeks and evaluation of lumbar spine and hip BMD by dual-energy X-ray absorptiometry (DXA) was conducted every 6 months. A blood sample for vitamin D and PTH measurements was obtained from adolescents who experienced >5% BMD loss. Vitamin D deficiency was defined as 25-hydroxyvitamin D (25OHD) level of <20 ng/mL, insufficiency as 25OHD level of 20-30 ng/mL, and sufficiency as 25OHD level of >30 ng/mL.Evaluation of vitamin D and PTH was carried out in 15 participants who experienced BMD loss of > or = 5% during DMPA use. At initiation of DMPA, participants had mean (+SE) age 17+1 years, gynecologic age 61+4 months, and body mass index 24+1.5 kg/m2. Racial/ethnic distribution was: Caucasian--7 girls, Hispanic--4 girls, African-American--3 girls, and other--1 girl. Six participants had BMD loss of >5% after 2 DMPA injections, five after 3 injections, one after 5 injections, one after 8 injections, one after 10 injections, and one after 13 injections. Only one girl (7%) had sufficient vitamin D. The other participants had vitamin D insufficiency (50%) or deficiency (43%). Participants' mean (+SE) PTH was 22+4 pg/mL (reference range 7-53 pg/mL), and mean (+SE) 1,25-dihydroxyvitamin D was 56+5 pg/mL (reference range 22-67 pg/mL).Inadequate vitamin D status was evident among the majority of female adolescents who experienced a substantial BMD loss while using DMPA.
View details for DOI 10.1016/j.jpag.2009.11.004
View details for Web of Science ID 000279744200004
View details for PubMedID 20471875
Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections
2010; 81 (4): 281-291
Depot medroxyprogesterone acetate (DMPA) is a highly effective progestin-only contraceptive that is widely used by adolescents. We investigated bone mineral density (BMD) changes in female adolescents during and following use of this method.A multicenter, prospective, non-randomized observational study in 98 healthy female adolescents aged 12-18 years who initiated DMPA intramuscular injections for contraception and provided BMD data for up to 240 weeks while receiving DMPA and for up to 300 weeks after DMPA cessation. BMD at the lumbar spine (LS), total hip (TH) and femoral neck (FN) was assessed by dual-energy X-ray absorptiometry. A mixed model analysis of variance was used to examine BMD changes.At the time of their final DMPA injection, participants had mean BMD declines from baseline of 2.7% (LS), 4.1% (TH) and 3.9% (FN) (p<.001 at all three sites). Within 60 weeks of discontinuation of DMPA, mean LS BMD had returned to baseline levels, and 240 weeks after DMPA discontinuation, the mean LS BMD was 4.7% above baseline. Mean TH and FN BMD values recovered to baseline values more slowly: 240 weeks and 180 weeks, respectively, after the last DMPA injection.BMD loss in female adolescents receiving DMPA for contraception is substantially or fully reversible in most girls following discontinuation of DMPA, with faster recovery at the LS than at the hip.
View details for DOI 10.1016/j.contraception.2009.11.003
View details for Web of Science ID 000276599500004
View details for PubMedID 20227543
RECOVERY OF BONE MINERAL DENSITY IN ADOLESCENTS FOLLOWING THE USE OF DEPOT MEDROXYPROGESTERONE ACETATE CONTRACEPTIVE INJECTIONS
ELSEVIER SCIENCE INC. 2010: S54–S54
View details for Web of Science ID 000274101600117
- Nutritional Factors that Influence Change in Bone Density and Stress Fracture Risk Among Young Female Cross-County Runners 7th International Symposium on Nutritional Aspects of Osteoporosis SPRINGER-VERLAG BERLIN. 2010: 145–147
International longitudinal pediatric reference standards for bone mineral content
2010; 46 (1): 208-216
To render a diagnosis pediatricians rely upon reference standards for bone mineral density or bone mineral content, which are based on cross-sectional data from a relatively small sample of children. These standards are unable to adequately represent growth in a diverse pediatric population. Thus, the goal of this study was to develop sex and site-specific standards for BMC using longitudinal data collected from four international sites in Canada and the United States. Data from four studies were combined; Saskatchewan Paediatric Bone Mineral Accrual Study (n=251), UBC Healthy Bones Study (n=382); Penn State Young Women's Health Study (n=112) and Stanford's Bone Mineral Accretion study (n=423). Males and females (8 to 25 years) were measured for whole body (WB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) BMC (g). Data were analyzed using random effects models. Bland-Altman was used to investigate agreement between predicted and actual data. Age, height, weight and ethnicity independently predicted BMC accrual across sites (P<0.05). Compared to White males, Asian males had 31.8 (6.8) g less WB BMC accrual; Hispanic 75.4 (28.2) g less BMC accrual; Blacks 82.8 (26.3) g more BMC accrual with confounders of age, height and weight controlled. We report similar findings for the PF and FN. Models for females for all sites were similar with age, height and weight as independent significant predictors of BMC accrual (P<0.05). We provide a tool to calculate a child's BMC Z-score, accounting for age, size, sex and ethnicity. In conclusion, when interpreting BMC in pediatrics we recommend standards that are sex, age, size and ethnic specific.
View details for DOI 10.1016/j.bone.2009.10.017
View details for Web of Science ID 000274129400026
View details for PubMedID 19854308
Clinical Review: Bisphosphonate Use in Childhood Osteoporosis
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2009; 94 (2): 400-409
As awareness of osteoporosis in childhood has increased, so have pressures to consider use of the pharmacological agents used to treat osteoporosis in adults. This review examines available research on the efficacy and safety of bisphosphonate therapy for pediatric osteoporosis.We reviewed the medical literature for key articles and consensus statements on the use of bisphosphonates in children through June 2008.We compared reports using varying bisphosphonate agents, doses, and duration of therapy to treat osteogenesis imperfecta and a variety of secondary causes of osteoporosis in children. Conclusions drawn from a recently published Cochrane analysis and the consensus statements from experts in the field were considered as well.Use of bisphosphonate therapy in pediatric patients remains controversial because of inadequate long-term efficacy and safety data. For this reason, many experts recommend limiting use of these agents to those children with recurrent extremity fractures, symptomatic vertebral collapse, and reduced bone mass. Current data are inadequate to support the use of bisphosphonates in children to treat reductions in bone mass/density alone. More research is needed to define appropriate indications for bisphosphonate therapy and the optimal agent, dose, and duration of use in pediatric patients.
View details for DOI 10.1210/jc.2008-1531
View details for Web of Science ID 000263072700011
View details for PubMedID 19033370
Use of bone biomarkers as an endpoint in a pediatric study of alendronate
72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals
WILEY-BLACKWELL. 2008: S721–S722
View details for Web of Science ID 000259244202003
Effect of oral contraceptives on weight and body composition in young female runners
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
2008; 40 (7): 1205-1212
To examine the effect of oral contraceptives (OC) on body weight, fat mass, percent body fat, and lean mass in young female distance runners.The study population consisted of 150 female competitive distance runners aged 18-26 yr who had participated in a 2-yr randomized trial of the effect of the OC Lo/Ovral (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) on bone health. Weight and body composition were measured approximately yearly by balance beam scales and dual-energy x-ray absorptiometry, respectively.Women randomized to the OC group tended to gain slightly less weight (adjusted mean difference (AMD) = -0.54 +/- 0.31 kg.yr, P = 0.09) and less fat (AMD = -0.35 +/- 0.25 kg.yr, P = 0.16) than those randomized to the control group. OC assignment was associated with a significant gain in lean mass relative to controls among eumenorrheic women (those who had 10 or more menstrual cycles in the year before baseline; AMD = 0.77 +/- 0.17 kg.yr, P < 0.0001) but not among women with fewer than 10 menstrual cycles in that year (AMD = 0.02 +/- 0.35 kg.yr, P = 0.96). Treatment-received analyses yielded similar results.This randomized trial confirms previous findings that OC use does not cause weight or fat mass gain, at least among young female runners. Our finding that this OC is associated with lean mass gain in eumenorrheic runners, but not in those with irregular menses, warrants examination in other studies.
View details for DOI 10.1249/MSS.0b013e31816a0df6
View details for Web of Science ID 000256981700002
View details for PubMedID 18580398
Longitudinal study of depot medroxyprogesterone acetate (Depo-Provera (R)) effects on bone health in adolescents: study design, population characteristics and baseline bone mineral density
2008; 77 (4): 239-248
This analysis was conducted to assess the baseline data and design methodology within an observational longitudinal comparison of use vs. nonuse of the injectable (intramuscular) contraceptive depot medroxyprogesterone acetate (DMPA-IM) and its effect on bone mass in adolescent women.A prospective, observational, open-label, unmatched-cohort, safety study in females aged 11-18 years. Participants either self-selected DMPA-IM (Depo-Provera) 150 mg to be administered every 12 weeks for up to 240 weeks with a 120-week post-treatment follow-up or were nonusers (users of nonhormonal contraception or sexually abstinent) who were to be followed up for up to 360 weeks. As each participant entered the study, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine, hip and femoral neck regions, along with total body bone mineral content; serum and urine specimens were obtained for assay of bone metabolism markers and participants' histories of parity and tobacco and alcohol use were obtained.A total of 389 participants were enrolled: 169 elected to begin DMPA-IM; 26 chose nonhormonal methods and 194 were abstinent. The baseline characteristics indicated significant disparities between DMPA-IM users and nonusers: compared with the nonusers, DMPA-IM users had more advanced chronologic and gynecologic ages, were more likely to have smoked, been pregnant and included more blacks. These factors would likely influence bone accretion rates independent of DMPA-IM exposure. Comparison of participant BMDs with standard reference data revealed that the study cohorts did not match reference populations closely enough to make a direct between-cohort comparative analysis feasible.The baseline differences in cohort characteristics preclude a meaningful comparison of mean BMD changes over time between DMPA-IM users and nonusers cohorts, and comparisons of changes in Z-scores between cohorts were also not appropriate. Therefore, within-participant BMD decreases from baseline were established as safety thresholds, and the proportion of individuals crossing those thresholds on a persistent or progressive basis was identified as the revised primary end point.
View details for DOI 10.1016/j.contraception.2007.11.002
View details for Web of Science ID 000254502900004
View details for PubMedID 18342646
Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents: The 2007 ISCD Pediatric Official Positions
JOURNAL OF CLINICAL DENSITOMETRY
2008; 11 (1): 43-58
The International Society for Clinical Densitometry Official Positions on reporting of densitometry results in children represent an effort to consolidate opinions to assist healthcare providers determine which skeletal sites should be assessed, which adjustments should be made in these assessments, appropriate pediatric reference databases, and elements to include in a dual energy X-ray absorptiometry (DXA) report. Skeletal sites recommended for assessment are the lumbar spine and total body less head, the latter being valuable as it provides information on soft tissue, as well as bone. Interpretation of DXA findings in children with growth or maturational delay requires special consideration; adjustments are required to prevent erroneous interpretation. Normative databases used as a reference should be based on a large sample of healthy children that characterizes the variability in bone measures relative to gender, age, and race/ethnicity, and should be specific for each manufacturer and model of densitometer and software. Pediatric DXA reports should provide relevant demographic and health information, technical details of the scan, Z-scores, and should not include T-scores. The rationale and evidence for development of the Official Positions are provided. Given the sparse data currently available in many of these areas, it is likely that these positions will change over time as new data become available.
View details for DOI 10.1016/j.jocd.2007.12.005
View details for Web of Science ID 000255568300005
View details for PubMedID 18442752
Pediatric randomized placebo-controlled trial of alendronate for glucocorticoid-associated osteoporosis
71st Annual Scientific Meeting of the American-College-of-Rheumatology/42nd Association-of-Rheumatology-Health-Professionals
WILEY-LISS. 2007: 4311–11
View details for Web of Science ID 000251781200188
Risk factors for stress fracture among young female cross-country runners
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
2007; 39 (9): 1457-1463
To identify risk factors for stress fracture among young female distance runners.Participants were 127 competitive female distance runners, aged 18-26, who provided at least some follow-up data in a randomized trial among 150 runners of the effects of oral contraceptives on bone health. After completing a baseline questionnaire and undergoing bone densitometry, they were followed an average of 1.85 yr.Eighteen participants had at least one stress fracture during follow-up. Baseline characteristics associated (P<0.10) in multivariate analysis with stress fracture occurrence were one or more previous stress fractures (rate ratio [RR] [95% confidence interval]=6.42 (1.80-22.87), lower whole-body bone mineral content (RR=2.70 [1.26-5.88] per 1-SD [293.2 g] decrease), younger chronologic age (RR=1.42 [1.05-1.92] per 1-yr decrease), lower dietary calcium intake (RR=1.11 [0.98-1.25] per 100-mg decrease), and younger age at menarche (RR=1.92 [1.15-3.23] per 1-yr decrease). Although not statistically significant, a history of irregular menstrual periods was also associated with increased risk (RR=3.41 [0.69-16.91]). Training-related factors did not affect risk.The results of this and other studies indicate that risk factors for stress fracture among young female runners include previous stress fractures, lower bone mass, and, although not statistically significant in this study, menstrual irregularity. More study is needed of the associations between stress fracture and age, calcium intake, and age at menarche. Given the importance of stress fractures to runners, identifying preventive measures is of high priority.
View details for DOI 10.1249/mss.0b013e318074e54b
View details for Web of Science ID 000249445700003
View details for PubMedID 17805074
Consensus and controversy regarding osteoporosis in the pediatric population.
2007; 13 (5): 513-520
To review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence.The medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis.Childhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass-variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise-associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients.Bone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood.
View details for PubMedID 17872354
The effect of oral contraceptives on bone mass and stress fractures in female runners
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
2007; 39 (9): 1464-1473
To determine the effect of oral contraceptives (OC) on bone mass and stress fracture incidence in young female distance runners.One hundred fifty competitive female runners ages 18-26 yr were randomly assigned to OC (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) or control (no intervention) for 2 yr. Bone mineral density (BMD) and content (BMC) were measured yearly by dual x-ray absorptiometry. Stress fractures were confirmed by x-ray, magnetic resonance imaging, or bone scan.Randomization to OC was unrelated to changes in BMD or BMC in oligo/amenorrheic (N=50) or eumenorrheic runners (N=100). However, treatment-received analyses (which considered actual OC use) showed that oligo/amenorrheic runners who used OC gained about 1% per year in spine BMD (P<0.005) and whole-body BMC (P<0.005), amounts similar to those for runners who regained periods spontaneously and significantly greater than those for runners who remained oligo/amenorrheic (P<0.05). Dietary calcium intake and weight gain independently predicted bone mass gains in oligo/amenorrheic runners. Randomization to OC was not significantly related to stress fracture incidence, but the direction of the effect was protective in both menstrual groups (hazard ratio [95% CI]: 0.57 [0.18, 1.83]), and the effect became stronger in treatment-received analyses. The trial's statistical power was reduced by higher-than-anticipated noncompliance.OC may reduce the risk for stress fractures in female runners, but our data are inconclusive. Oligo/amenorrheic athletes with low bone mass should be advised to increase dietary calcium and take steps to resume normal menses, including weight gain; they may benefit from OC, but the evidence is inconclusive.
View details for DOI 10.1249/mss.0b013e318074e352
View details for Web of Science ID 000249445700004
View details for PubMedID 17805075
Bone mineral density in postmenarchal adolescent girls in the United States: Associated biopsychosocial variables and bone turnover markers
27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
ELSEVIER SCIENCE INC. 2007: 44–53
During adolescence, bone formation prevails over resorption, resulting in accumulation of 40% of peak bone mass throughout this time period. Although multiple studies have explored bone mass accrual during the early stages of puberty, less is known about factors that may influence bone accrual during later years of adolescence. In the present cross-sectional study we examined relationships among bone mineral density (BMD) and demographic factors, behavioral variables, and bone metabolism markers in postmenarchal adolescent girls.The population was comprised of 389 healthy postmenarchal adolescent girls aged 11-18 years, who were recruited into a prospective study of the effect of depot medroxyprogesterone acetate (DMPA) on bone health in adolescents. At the baseline visit, investigators collected demographic, reproductive health, and lifestyle data, and performed a complete physical examination. Body mass index (BMI) was calculated. Before study initiation, BMD at the lumbar spine, total hip, and femoral neck was measured by dual-energy X-ray absorptiometry (DXA), and markers of bone metabolism (serum bone-specific alkaline phosphatase [BAP], serum osteocalcin, and urinary N-telopeptide [uNTX]) were measured. The baseline data from this study were analyzed to evaluate possible correlates of BMD in postmenarchal adolescent girls. Potential associations between BMD values and other parameters were assessed by analysis of variance and Pearson's correlation coefficient.Participants enrolled in the study had a mean (+/- SD) chronological age of 14.9 +/-1.7 years (range 11-18), mean gynecologic age of 39.9 +/-23.0 months (range 1-120) postmenarche, and mean BMI of 23.5 +/-4.6 kg/m(2) (range 16.0-42.2). Racial/ethnic distribution was 46% African American, 35% Caucasian, and 19% other races; 9% had previously been pregnant. Positive correlations were observed between lumbar spine BMD and chronological age (r = .301, p < .0001), gynecologic age (r = .349, p < .0001), and BMI (r = .371, p < .0001). Total hip and femoral neck BMD values were significantly higher (p < .05 and p < .05, respectively) in African American participants compared with non-African American participants. Previous history of pregnancy was significantly associated with a lower BMD at the lumbar spine (p < .0001) and the total hip (p < .01) when compared with the BMD of adolescents who had never been pregnant. Cigarette smoking and alcohol use were not associated with significant differences in BMD. Negative correlations were observed between gynecologic age and the levels of BAP (r = -.564, p < .0001), osteocalcin (r = -.349, p < .0001), and uNTX (r = -.281, p < .0001), and between lumbar spine BMD and BAP (r = -.363, p < .0001), osteocalcin (r = -.129, p < .05), and uNTX (r = -.202, p < .001) levels.Our data demonstrate that chronological age, gynecologic age, race/ethnicity, BMI, and previous history of pregnancy are markedly associated with BMD in postmenarchal adolescent girls. Bone accretion in the postmenarchal years continues in the face of a slowdown in bone turnover during this time period.
View details for DOI 10.1016/j.jadohealth.2006.08.013
View details for Web of Science ID 000243183000006
View details for PubMedID 17185205
Variable deficits of bone mineral despite chronic glucocorticoid therapy in pediatric patients with inflammatory diseases: A glaser pediatric research network study
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
2006; 19 (6): 821-830
To evaluate the relationship between chronic glucocorticoid (GC) exposure and bone mineral density (BMD) in children with rheumatic diseases and inflammatory bowel disease.Lumbar spine BMD was measured by DXA in 86 GC-treated children (66% female, age 8-20 years, mixed ethnicity) screened for a multi-center intervention trial. Predictors of spine BMD z-score and vitamin D [25(OH)D] were examined by multivariable linear regression.Mean prior year and lifetime cumulative GC exposure was 77.8 mg/kg and 224.6 mg/kg, respectively. BMD z-scores ranged from -3.7 to 2.2 SD (-1.1 +/- 1.2, mean +/- SD). Lower BMD z-scores were associated with increased prior year average daily GC dose (p = 0.03), decreased height z-score (p = 0.003), and decreased 25(OH)D concentrations (p = 0.03), but explained only a small proportion of BMD variability (adjusted R2 = 0.29). The 25(OH)D levels were <20 ng/ml in 45% of patients, and low 25(OH)D was associated with non-Caucasian ethnicity (p <0.001), increased age (p = 0.004), increased parathyroid hormone (p = 0.03), and residing in the Boston area (p <0.001).Although GC exposure is significantly associated with BMD z-score, the association is too variable to serve as a consistent predictor of reduced BMD in children. Vitamin D insufficiency is common and may contribute to skeletal deficits in this population.
View details for Web of Science ID 000239138500006
View details for PubMedID 16886590
Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2006; 91 (5): 1862-1867
Dosing of monthly depot leuprolide (DL) in central precocious puberty (CPP) varies considerably. U.S. practitioners use 7.5-15 mg, in contrast with the international standard of 3.75 mg. Pubertal suppression using the newer 3-month DL also has been reported from Europe. To date there have been no direct comparisons of these different DL doses.In an open 12-month protocol, we tested the efficacy of three DL doses (7.5 mg- and 3.75 mg-1 month and 11.25 mg-3 month) given sequentially to subjects treated for CPP. Primary outcome measures were stimulated gonadotropin (Gn) levels at 12-wk intervals. The null hypothesis was no difference among doses.Both existing and new patients with CPP received our standard therapy (DL 7.5 mg every 4 wk) for a minimum of 24 wk. In subjects with DL-stimulated LH 2 IU/liter or less, the dose was changed to 3.75 mg every 4 wk and evaluated 12 wk later. Subjects who met LH criteria (<4.5 IU/liter) on 3.75 mg then received a single dose of 11.25 mg-3 month and were reevaluated 12 wk later. Serum LH/FSH and sex steroids were obtained 40 min after DL injection.Thirty subjects were enrolled (20 naive; 24 girls, 6 boys), and 21 were evaluated on all three DL doses. DL-stimulated LH levels (mean +/- sd) were 1.30 +/- 0.74, 1.73 +/- 0.99, and 2.13 +/- 1.41 on 7.5 mg, 3.75 mg, and 11.25 mg-3 month, respectively (7.5 vs. 3.75 mg, P = 0.019; 7.5 mg vs. 11.25 mg-3 month, P = 0.004, Wilcoxon ranked sign test). Mean FSH levels were 2.86 +/- 1.91, 3.91 +/- 1.98, and 3.96 +/- 1.34, respectively (7.5 vs. 3.75 mg, P = 0.017; 7.5 mg vs. 11.25 mg-3 month, P = 0.020). No differences were detected in mean sex steroid levels.Stimulated LH and FSH levels were significantly higher during therapy with both the 3.75 mg and 11.25 mg-3 month depot leuprolide doses, compared with 7.5 mg, contradicting the null hypothesis of no difference. These data suggest that low-dose 1- and 3-month DL preparations are associated with persistently greater gonadal stimulation in most CPP patients, but the LH/FSH results were not corroborated by differences in sex steroid levels. Whether various DL doses lead to long-term therapeutic differences remains to be determined.
View details for DOI 10.1210/jc.2005-1500
View details for Web of Science ID 000237330000037
View details for PubMedID 16449344
Measuring bone mass in children: Can we really do it?
Symposium on Pubertal Growth - The Critical State for the Attainment and Maintenance of Skeletal Health
KARGER. 2006: 11–16
Bone densitometry is used to assess skeletal health in clinical and research settings, with the goal of achieving reproducible measurements of bone mass that help to identify individuals predisposed to fracture. The search is now on for better methods of capturing additional factors that contribute to bone strength, including bone size, geometry, microarchitecture, and turnover rates. This has proved particularly challenging in growing children, whose bones continually change in size, shape, and mass. Dual energy X-ray absorptiometry is the preferred method for measuring bone mass in children, but the technique has several limitations, and interpreting the findings can be problematic. Peripheral quantitative computed tomography is a promising method for assessing bone mass and other indices correlating with bone strength, but a lack of precision and paediatric norms currently restricts its clinical utility. Although bone mineral density is predictive of future fracture risk in adults, the evidence in children is less conclusive, and a diagnosis of osteoporosis in a child should not be made on densitometric findings alone. Developing a clearer understanding of how measures of bone mass and strength correlate with bone fracture in children will help target preventive strategies for those in greatest need.
View details for DOI 10.1159/000091749
View details for Web of Science ID 000237970500003
View details for PubMedID 16707904
The relative contributions of lean tissue mass and fat mass to bone density in young women
17th International Congress of Nutrition
ELSEVIER SCIENCE INC. 2005: 474–81
Although obesity is associated with increased risk of many chronic diseases including cardiovascular disease, diabetes, hypertension, and cancer, there is little evidence to suggest that obesity increases risk of osteoporosis. In fact, both weight and body mass index (BMI) are positive predictors of bone mass in adults, suggesting that those who are overweight or obese may be at lower risk of osteoporosis. However, recent evidence suggests that in children and adolescents, obesity may be associated with lower rather than higher bone mass. To understand the relation of fat mass to bone mass, we examined data gathered from an ethnically diverse group of 921 young women, aged 20-25 years (317 African Americans, 154 Asians, 322 Caucasians, and 128 Latinas) to determine how fat mass (FM) as well as lean tissue mass (LTM) is associated with bone mass. Bone mass, FM, and LTM were measured using dual energy X-ray absorptiometry (GE Lunar Corp, Madison, WI). Bone mass was expressed as bone mineral density (BMD; g/cm2) and bone mineral apparent density (BMAD; g/cm3) for the spine and femoral neck, and as BMD and bone mineral content (BMC; g) for the whole body. Regression techniques were used to examine the following: (1) in separate equations, the associations of LTM and FM with each bone mass parameter; and (2) in the same equation, the independent contributions of LTM and FM to bone mass. LTM and FM were positively correlated with BMD at all skeletal sites. When the contributions of FM and LTM were examined simultaneously, both FM and LTM continued to be positively associated with bone mass parameters but the effect of FM was noted to be smaller than that of LTM. We conclude that in young women, LTM has a greater effect than fat mass on bone density per kg of tissue mass.
View details for DOI 10.1016/j.bone.2005.04.038
View details for Web of Science ID 000232264800006
View details for PubMedID 16040285
Determinants of bone mineral density in female adolescents.
27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
WILEY-BLACKWELL. 2005: S106–S106
View details for Web of Science ID 000233503801134
Osteoporosis and measurement of bone mass in children and adolescents
ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
2005; 34 (3): 521-?
Osteoporosis increasingly is recognized as a pediatric concern. Fragility fractures occur in children and adolescents with genetic disorders and those with a variety of chronic diseases. Others may not fracture in childhood but reach adulthood with a reduced peak bone mass and increased lifelong risk of osteoporosis. This article reviews the indications for pediatric bone density testing, the strengths and limitations of densitometry methods, and the challenges of interpreting the results. The goals are to demystify the densitometry report and to clarify the role of bone density tests in assessing and managing skeletal health in children.
View details for DOI 10.1016/j.ecl.2005.04.001
View details for Web of Science ID 000231677400003
View details for PubMedID 16085157
Depot medroxyprogesterone acetate (Depo-Provera (R) 150 mg; DMPA-IM) and bone mineral density in adolescents: Study design, population characteristics, and baseline bone mineral density
3rd International Conference on Childrens Bone Health
ELSEVIER SCIENCE INC. 2005: S62–S63
View details for Web of Science ID 000229249300138
- Consensus statement: Guide to bone health and disease in cystic fibrosis JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 2005; 90 (3): 1888-1896
Assessing bone health in children: who to test and what does it mean?
Pediatric endocrinology reviews : PER
2005; 2: 332-336
The foundation of bone health is established during childhood and adolescence. Unfortunately, pediatric bone health may be threatened in a variety of genetic and acquired disorders. Low bone mineral density (BMD) and/or fragility fractures may result. This paper addresses the pediatric indications for bone densitometry testing in children at risk for poor bone health and the challenges of interpreting the results. Dual energy x-ray absorptiometry (DXA) is the most commonly used of the bone densitometry methods. Most DXA software programs report BMD in terms of a T-score, which compares the results to adult norms. Z-scores, based upon age- and gender-matched reference data, should be used instead to avoid the mislabeling of a child as "osteoporotic." Delayed growth and maturation also complicate the interpretation of DXA findings in chronically ill patients. Although children with low BMD values may have an increased risk of fracture, a pediatric "fracture threshold" has not been established. Further research is needed to refine the indications for bone density testing in children and to aid in the interpreting the results.
View details for PubMedID 16456501
- Taking steps towards reducing osteoporosis in Duchenne Muscular Dystrophy NEUROMUSCULAR DISORDERS 2005; 15 (1): 86-87
Predicting low bone mineral density in childhood inflammatory diseases: Experience from a glaser pediatric research network alendronate trial.
26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
WILEY-BLACKWELL. 2004: S470–S470
View details for Web of Science ID 000224326802599
Normal bone geometry but reduced bone mineral at the femoral neck with cystic fibrosis.
26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
WILEY-BLACKWELL. 2004: S237–S237
View details for Web of Science ID 000224326801303
Vitamin D insufficiency is common among pediatric subjects participating in an osteoporosis treatment trial: A glaser pediatric research network study.
68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals
WILEY-BLACKWELL. 2004: S538–S538
View details for Web of Science ID 000223799001468
Predicting low bone mineral density (BMD) in childhood inflammatory diseases: Experience from a giaser pediatric research network alendronate treatment trial.
68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals
WILEY-BLACKWELL. 2004: S537–S537
View details for Web of Science ID 000223799001467
Official positions of the International Society for Clinical Densitometry
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2004; 89 (8): 3651-3655
The International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences for the purpose of establishing standards and guidelines for indications, acquisition, and interpretation of bone density tests. Topics are selected for consideration by the ISCD Scientific Advisory Committee, reviewed by scientific working groups, and presented to an international panel of experts. Topic categories addressed to date include indications for bone density testing, selection of reference databases for T-scores and Z-scores, clinical applications for central and peripheral bone densitometry, serial bone density testing, instrument precision assessment, phantom scanning and calibration testing, requirements for a bone density report, nomenclature, and diagnosis of osteoporosis in postmenopausal women, premenopausal women, men, and children. After an open session for public comment and discussion, the panel convenes for consideration of each topic and makes recommendations for positions to the ISCD Board of Directors. Recommendations that are accepted become the Official Positions of the ISCD. This Special Report summarizes the methodology of the ISCD Position Development Conferences and presents selected Official Positions of general interest.
View details for DOI 10.1210/jc.2004-0124
View details for Web of Science ID 000223072400003
View details for PubMedID 15292281
Bone health in children and adolescents: a symposium at the annual meeting of the Pediatric Academic Societies/Lawson Wilkins Pediatric Endocrine Society, May 2003.
Current problems in pediatric and adolescent health care
2004; 34 (6): 226-242
View details for PubMedID 15232554
Standards and guidelines for performing central dual-energy X-ray absorptiometry in premenopausal women, men, and children - A report from the Canadian panel of the International Society of Clinical Densitometry
Conference of the International-Society-for-Clinical-Densitometry-Position-Development
ELSEVIER SCIENCE INC. 2004: 51–63
View details for Web of Science ID 000235562000008
Patients with cystic fibrosis have normal bone geometry but reduced bone mineral.
25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
WILEY-BLACKWELL. 2003: S320–S320
View details for Web of Science ID 000186080501284
Bone mineral density in pediatric transplant recipients
2003; 76 (4): 673-678
Reduced bone mass and fragility fractures are known complications after transplantation in adults. Far less is known about the skeletal effects of transplantation in children and adolescents.This cross-sectional study examined the skeletal status of children (ages 9-18 years) who were at least 1 year post-cardiac (n=13), post-renal (n=8), or post-bone marrow (BMT; n=15) transplantation. Bone mass at total hip, femoral neck, spine (L2-4), and whole body (WB) was determined by dual energy x-ray absorptiometry and compared with age, sex, and ethnic-specific reference data. Standard deviations (z-scores) were calculated for both areal bone mineral density (BMD) and estimated volumetric bone density (bone mineral apparent density [BMAD]).Cardiac transplant patients had significantly lower BMD z-scores compared with the reference population at all skeletal sites. BMT recipients had significantly reduced BMD z-scores at total hip, spine, and WB. Kidney transplant patients had a significantly reduced WB BMD z-score only. Spine BMAD z-scores remained significantly reduced in cardiac and BMT subjects. Three of 36 patients had radiographic evidence of spinal fracture after transplantation. No correlation between steroid dosage and any measure of bone mass was observed.Cardiac and BMT recipients had reduced BMD at multiple skeletal sites, and renal transplant recipients had reduced WB BMD for age. Deficits in spine bone density persisted after correcting for small bone size using BMAD. Low bone density and the occurrence of vertebral fractures indicate that cardiac, renal, and bone marrow transplantation in children is associated with reduced bone health.
View details for DOI 10.1097/01.TP.0000076627.70050.53
View details for Web of Science ID 000185135100011
View details for PubMedID 12973107
Low-dose intravenous pamidronate reduces fractures in childhood osteoporosis
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
2003; 16 (6): 887-892
Despite the proven efficacy of low-dose pamidronate in adults with osteoporosis, the efficacy of the low-dose regimen in children has not been studied. Pamidronate (1 mg/kg) was administered intravenously once every 3 months to 11 children with osteoporosis. Treatment was associated with reduced fracture rates and increased areal (BMD) and volumetric (BMAD) bone mineral density measured by dual energy X-ray absorptiometry (DXA). The mean annualized percent gain was 20.1 +/- 16.9 (4.7 to 59.1, n = 9) for spinal BMD and 15.1 +/- 18.1 (-11.0 to 40.2, n = 9) for spinal BMAD. Common adverse effects including fever, muscle aches, nausea and fatigue were self-limited and generally occurred only after the first infusion. Clinically significant hypocalcemia did not occur. Low-dose pamidronate appears promising in the treatment of childhood osteoporosis.
View details for Web of Science ID 000186609700011
View details for PubMedID 12948302
Disordered eating, menstrual irregularity, and bone mineral density in female runners
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
2003; 35 (5): 711-719
To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners.Subjects were 91 competitive female distance runners aged 18-26 yr. Disordered eating was measured by the Eating Disorder Inventory (EDI). Menstrual irregularity was defined as oligo/amenorrhea (0-9 menses per year). BMD was measured by dual x-ray absorptiometry.An elevated score on the EDI (highest quartile) was associated with oligo/amenorrhea, after adjusting for percent body fat, age, miles run per week, age at menarche, and dietary fat, (OR [95% CI]: 4.6 [1.1-18.6]). Oligo/amenorrheic runners had lower BMD than eumenorrheic runners at the spine (-5%), hip (-6%), and whole body (-3%), even after accounting for weight, percent body fat, EDI score, and age at menarche. Eumenorrheic runners with elevated EDI scores had lower BMD than eumenorrheic runners with normal EDI scores at the spine (-11%), with trends at the hip (-5%), and whole body (-5%), after adjusting for differences in weight and percent body fat. Runners with both an elevated EDI score and oligo/amenorrhea had no further reduction in BMD than runners with only one of these risk factors.In young competitive female distance runners, (i) disordered eating is strongly related to menstrual irregularity, (ii) menstrual irregularity is associated with low BMD, and (iii) disordered eating is associated with low BMD in the absence of menstrual irregularity.
View details for DOI 10.1249/01.MSS.0000064935.68277.E7
View details for Web of Science ID 000182714200001
View details for PubMedID 12750578
Comparison of calcaneus ultrasound and dual X-ray absorptiometry in children at risk of osteopenia
JOURNAL OF CLINICAL DENSITOMETRY
2003; 6 (1): 7-15
The optimal method to assess pediatric bone mass remains controversial. Dual X-ray absorptiometry (DXA) is used most commonly for clinical assessments in children, but calcaneus ultrasound (CUS) is less costly, is free of ionizing radiation, and predicts fracture as well as DXA in adults. This study was designed to compare CUS and DXA in 42 young patients (ages 9-21) with chronic disease and/or fragility fractures. Zscores for broadband ultrasound attenuation (BUA) and speed of sound (SOS) determined using the Lunar Achilles Plus ultrasonometer were compared with Z-scores for areal bone mineral density (BMD) and volumetric BMD using DXA (Hologic). Logistic regression was employed to predict low bone density measured by DXA (defined as spinal BMD Z-score < -2) from CUS measurements. Sensitivity/specificity analysis was performed to compare CUS and spinal DXA Z-scores as predictors of previous low-impact fracture. Correlations between CUS and DXA Z-scores were in the range of r = 0.3-0.6. Areas under the receiver operator characteristic (ROC) curves for BUA and SOS predicting low bone density by DXA were similar: 0.81 and 0.82, respectively. ROC curve areas for spinal DXA, BUA, and SOS predicting previous fracture were also similar: 0.85, 0.84, and 0.84, respectively. While CUS correlates only modestly with DXA, ROC curve areas indicate that CUS detects low bone mineral in children with fragility fractures as well as DXA and may be a viable initial screen for osteopenia.
View details for Web of Science ID 000180842000002
View details for PubMedID 12665697
Diet in midpuberty and sedentary activity in prepuberty predict peak bone mass
17th International Congress of Nutrition
AMER SOC NUTRITION-ASN. 2003: 495–503
An average daily calcium intake of 1300 mg is recommended for North American adolescents aged 9-18 y. However, questions remain about these recommendations.We assessed whether there is a stage of puberty when dietary calcium is more strongly related to peak bone mass, as indicated by young adult bone mass (YABM); whether dietary calcium intake > 1000 mg/d in adolescence is associated with higher YABM; and whether race affects any of these associations between dietary calcium and YABM. Secondarily, we evaluated relations between sedentariness and YABM.In a retrospective cohort study, we recruited 693 black and white women aged 21-24 y who had participated in the 10-y National Heart, Lung, and Blood Institute Growth and Health Study and measured YABM with the use of dual-energy X-ray absorptiometry. Dietary calcium and sedentary activity data, gathered through 3-d food records and self-reports of television-video viewing at 8 annual examinations, were averaged over 3 pubertal stages. Complete data were available from 161 black and 180 white females. Multiple regression, controlling for race, weight, and height, was applied to assess diet and activity relations with YABM.Dietary calcium was most strongly associated with YABM in midpuberty. Calcium intake > 1000 mg/d was associated with higher YABM, but this association was not significant at all skeletal sites. Race did not affect the observed relations between calcium and YABM. Sedentary activity in prepuberty was inversely associated with YABM.Interventions should focus on ensuring adequate calcium intake in midpuberty and on minimizing sedentariness in prepuberty.
View details for Web of Science ID 000180512200032
View details for PubMedID 12540413
Ethnic differences in bone mass of young women vary with method of assessment
JOURNAL OF CLINICAL DENSITOMETRY
2002; 5 (3): 229-238
To examine ethnic differences in bone mass measured by calcaneus ultrasound (CUS) and dual energy X-ray absorptiometry (DXA), and to compare the two methodologies, CUS was performed in 904 healthy Asian, African American, Latina, and Caucasian women 20-26 yr old using the Lunar Achilles Plus ultrasonometer. CUS measurements (broadband ultrasound attenuation [BUA] and speed of sound [SOS]) were made following standard methodology (standard CUS) and repeated adjusting for foot size using shims (with-shim CUS). Areal bone mineral density (BMD) and estimated volumetric bone density (BMAD) at the spine, femoral neck, and whole body were determined using the Lunar DPX-IQ. African Americans had greater height- and weight-adjusted BUA than Caucasians, while Asians and African Americans had greater SOS than Caucasians and Latinas. Additionally, African Americans had greater height- and weight-adjusted BMD and BMAD than all other groups. CUS and DXA measurements correlated moderately (r = 0.2-0.5). With-shim CUS values were 0.9-7.8% lower than standard CUS values. In conclusion, African American women had greater DXA measurements than all others and greater CUS measurements than Caucasians. In contrast to DXA, CUS measurements in Asians and Latinas were not significantly lower than those in African Americans. Most notably, Asians had greater values for SOS than Caucasians and Latinas. Discrepancies in ethnic comparisons and modest correlations suggest that CUS and DXA methods may capture different bone qualities.
View details for Web of Science ID 000178747500002
View details for PubMedID 12357060
Calcaneus ultrasound measurements in a convenience sample of healthy youth
JOURNAL OF CLINICAL DENSITOMETRY
2001; 4 (2): 111-120
We examined age-related changes in quantitative ultrasound of the calcaneus in 311 healthy males and females ages 6.6-20 yr using the Lunar Achilles ultrasound device. This equipment has been adapted for pediatric use with the provision of shims designed to properly position smaller feet relative to the transducers. Broadband ultrasound attenuation (BUA) (decibels/megahertz), speed of sound (SOS) (meters/second), and stiffness index (SI) (percent) increased across the age range until a plateau was reached at 16-18 yr. BUA increased by 40%, SOS by 4%, and SI by 80% across this age range. There was no gender difference in age-related gains. Age, weight, height, and hours of weight-bearing physical activity were all significantly associated with BUA, SOS, and SI. After controlling for age and weight, hours of weight-bearing physical activity showed little to no additional effect on these parameters. Short-term in vivo precision using this device was similar in children to that observed in adults in our laboratory; coefficients of variation for between-day measurements were 1.8, 0.6, and 3.2% for BUA, SOS, and SI, respectively. These data support the feasibility of using the Lunar Achilles in evaluating pediatric bone mass. The ability of this technique to discriminate between osteopenic and normal children remains to be determined.
View details for Web of Science ID 000169903600004
View details for PubMedID 11477304
Acquisition of optimal bane mass in childhood and adolescence
TRENDS IN ENDOCRINOLOGY AND METABOLISM
2001; 12 (1): 22-28
Peak bone mass (PBM), which is achieved by early adulthood, is a key determinant of the lifetime risk of osteoporosis. Because the foundation for skeletal health is established so early in life, osteoporosis prevention begins by optimizing gains in bone mineral throughout childhood and adolescence. Heritable factors account for an estimated 60-80% of the variability in PBM, with diet, physical activity and hormonal status serving as important modifiers of bone accrual. Recent pediatric studies have clarified the tempo and magnitude of gains in bone mineral and the modulating effects of diet, activity and sex steroids. The challenge lies in designing effective means to reverse trends of decreased calcium consumption, increased sodium intake and diminished physical activity among children and adolescents. Equally important is raising the awareness of health care providers to recognize children at risk for suboptimal acquisition of PBM.
View details for Web of Science ID 000168720500005
View details for PubMedID 11137037
- Depot medroxyprogesterone acetate in teens: A risk for bone health? PEDIATRICS 2000; 106 (5): 1137-1138
Dual energy X-ray absorptiometry (DEXA) measurements of bone density and body composition: Promise and pitfalls
13th Annual Meeting of the National Cooperative Growth Study (NCGS)
FREUND PUBLISHING HOUSE LTD. 2000: 983–988
Dual energy X-ray absorptiometry (DEXA) is widely viewed as the preferred method to assess pediatric bone mineral content because of its speed, precision, and minimal radiation exposure, and the availability of pediatric reference data. DEXA can also be used to estimate body composition precisely with minimal patient cooperation. Accurate interpretation of DEXA data in children requires consideration of bone size, pubertal stage, skeletal maturation, ethnicity and body composition. Bone mineral content may be underestimated in smaller children and overestimated in larger ones. Corrections for skeletal age or sexual maturity may also be needed in children with advanced or delayed growth. Errors in body composition measurement occur because body fat and fat-free mass are not distributed uniformly. In addition, fat mass present adjacent to bone will influence the measurement of bone mineral content. In conclusion, DEXA is a valuable tool for assessing pediatric bone health, but accurate interpretation of densitometry results requires recognition of a myriad of pitfalls.
View details for Web of Science ID 000090130500003
View details for PubMedID 11086651
Use of hormone replacement therapy to reduce the risk of osteopenia in adolescent girls with anorexia nervosa
JOURNAL OF ADOLESCENT HEALTH
2000; 26 (5): 343-348
To assess how commonly hormone replacement therapy (HRT) and other measures are prescribed for the treatment of osteopenia in children and adolescents with anorexia nervosa (AN).A self-administered questionnaire was distributed and completed by allopathic and osteopathic physician members of the Society for Adolescent Medicine at its 1998 annual meeting. The questionnaire was also mailed and E-mailed between March 1998 and February 1999. Descriptive statistics included percentages and measures of central tendency.The questionnaire was completed by 394 of the 1029 physicians surveyed (38.3%). Of the 268 respondents who treated patients with AN under the age of 18 years, 77.6% prescribed HRT. The decision to prescribe HRT was influenced by patient's age but not by bone mineral status. Among those who prescribed HRT, additional therapies included increased caloric intake (89.4%), weight gain (82.2%), increased calcium intake (84.1%), a change in exercise patterns (59.1%), and vitamin D supplementation (37.0%). Only 59 (22.0%) did not use HRT as a treatment modality. One-third of nonprescribers cited the lack of evidence of efficacy of HRT in preventing osteopenia. More recent medical graduates were less likely to prescribe HRT.This survey suggests that practitioners caring for adolescent females with AN commonly prescribe HRT for the treatment of osteopenia despite the paucity of evidence demonstrating that it effectively prevents or reverses bone loss associated with this disorder.
View details for Web of Science ID 000086593200007
View details for PubMedID 10775827
Mechanobiology of femoral neck structure during adolescence
JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT
2000; 37 (2): 201-208
Understanding femoral neck structure may be critical to preventing fractures at this site. We examined the correlates of changes in the femoral neck during adolescence. Dual energy x-ray absorptiometry measurements of proximal femora were made in 101 Caucasian youths (ages 9 to 26 years). Relationships were examined between developmental parameters (age, pubertal stage, height, body mass, lean mass, and fat mass) and femoral structure (bone mineral content, bone mineral density, neck width, cross-sectional area, and cross-sectional strength). Lean body mass was the best predictor of femoral neck structure, explaining 53-87 percent of the variance, and was independent of gender. Body mass only explained 51-79 percent of the variance. Previously we found body mass to be the strongest predictor of femoral mid-diaphyseal cross-sectional properties. These findings suggest that trabecular bone of the femoral neck may be more responsive to its mechanical environment than the cortical diaphysis. In addition, lean body mass may be a more reliable predictor of muscle loading than body mass.
View details for Web of Science ID 000165733400013
View details for PubMedID 10850826
Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth: A longitudinal study
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
1999; 84 (12): 4702-4712
Ethnic and gender differences in bone mineral acquisition were examined in a longitudinal study of 423 healthy Asian, black, Hispanic, and white males and females (aged 9-25 yr). Bone mass of the spine, femoral neck, total hip, and whole body was measured annually for up to 4 yr by dual energy x-ray absorptiometry. Age-adjusted mean bone mineral curves for areal (BMD) and volumetric (BMAD) bone mineral density were compared for the 4 ethnic groups. Consistent differences in areal and volumetric bone density were observed only between black and nonblack subjects. Among females, blacks had greater mean levels of BMD and BMAD at all skeletal sites. Differences among Asians, Hispanics, and white females were significant for femoral neck BMD, whole body BMD, and whole body bone mineral content/height ratio, for which Asians had significantly lower values; femoral neck BMAD in Asian and white females was lower than that in Hispanics. Like the females, black males had consistently greater mean values than nonblacks for all BMD and BMAD measurements. A few differences were also observed among nonblack male subjects. Whites had greater mean total hip BMD, whole body BMD, and whole body bone mineral content/height ratio than Asian and Hispanic males; Hispanics had lower spine BMD than white and Asian males. The tempo of gains in BMD varied by gender and skeletal site. In females, total hip, spine, and whole body BMD reached a plateau at 14.1, 15.7, and 16.4 yr, respectively. For males, gains in BMD leveled off at 15.7 yr for total hip and at age 17.6 yr for spine and whole body. Black and Asian females and Asian males tended to reach a plateau in BMD earlier than the other ethnic groups. The use of gender- and ethnic-specific standards is recommended when interpreting pediatric bone densitometry data.
View details for Web of Science ID 000084134100065
View details for PubMedID 10599739
Natural history of growth hormone receptor deficiency
25th International Symposium on Growth Hormone and Growth Factors in Endocrinology and Metabolism/3rd International Workshop on Growth Hormone Insensitivity
BLACKWELL PUBLISHING. 1999: 153–156
This review discusses the natural history of growth hormone receptor deficiency (GHRD) in relation to epidemiology, mortality, growth, certain aspects of body composition, and intellectual development. The majority of affected individuals are of Semitic origin and 90% come from the Indian peninsula, the Middle East, or elsewhere in the Mediterranean. There is a twofold increased mortality before the age of 7 years for children with GHRD. Affected adults may have increased cardiovascular risk resulting from increased total cholesterol and low-density lipoprotein cholesterol, unrelated to adiposity or insulin resistance. Intrauterine growth is affected minimally, if at all. Within a genetically homogeneous population in Ecuador, postnatal growth effects are as variable as in a large genetically heterogeneous population. There is no influence of parental heights. Areal bone mineral density is reduced in adults with GHRD, but estimated volumetric bone density (bone mineral apparent density) is normal. Intellectual development is unaffected by GHRD.
View details for Web of Science ID 000079031600033
View details for PubMedID 10102072
A comparison of calcaneus ultrasound and dual X-ray absorptiometry in healthy north American youths and young adults
JOURNAL OF CLINICAL DENSITOMETRY
1999; 2 (4): 403-411
Quantitative ultrasound is the newest noninvasive method to be accepted for assessing bone mineral in adults. Heel ultrasound measurements correlate with bone density measurements by dual X-ray absorptiometry (DXA) and predict fracture risk in adults. Far less is known about the value of calcaneus ultrasound (CUS) in children. We determine spine, femoral neck, and whole-body bone mineral by DXA and heel bone mass by CUS in 125 youths (69 females, 56 males) ages 9-25 yr. CUS and DXA measurements of bone mass increased with age and pubertal development during adolescence in a parallel fashion. Among females, Tanner stage was a stronger predictor than age for all CUS and DXA measurements, and among males, pubertal stage was a stronger predictor for spine bone mineral apparent density (BMAD) and femoral bone mineral density (BMD). CUS measurements correlated moderately well with DXA measurements of the spine, femoral neck, and whole-body BMD and spine BMAD (r = 0.23-0.58, p < 0. 008). CUS warrants further study as a tool for assessing bone mineral acquisition in children.
View details for Web of Science ID 000085084200007
View details for PubMedID 10677794
Influence of pre-adolescent diet on quantitative ultrasound measurements of the calcaneus in young adult women
1999; 9 (6): 532-535
Nongenetic determinants of quantitative ultrasound (QUS) properties of the bone remain to be identified. The purpose of this study was to determine relationships between early adolescent diet and QUS bone measurements taken in young adulthood. Subjects were participants in the 10-year longitudinal National Heart, Lung, and Blood Institute Growth and Health Study (NGHS). QUS parameters measured at the calcaneus in a convenience subsample of 63 18- to 19-year-old black and white women were correlated with dietary data collected when the subjects were aged 9-11 years. We hypothesized that pre-adolescent intake of calcium, magnesium, vitamin C and protein, nutrients known to be associated with bone development, would be associated with QUS measurements in young women. Stepwise multiple regression analysis, controlling for race, height and weight, demonstrated that pre-adolescent intake of calcium and magnesium were positively related to QUS parameters (calcium with broadband ultrasound attenuation, and magnesium with speed of sound and bone velocity). Our findings suggest that pre-adolescent diet may be associated with bone properties as measured by ultrasound. Further investigations of this relationship may yield a deeper understanding of the impact of diet on skeletal development. The small size of the convenience sample used for the analysis precludes stronger inferences at this time.
View details for Web of Science ID 000081773200010
View details for PubMedID 10624461
Two measures of physical activity as predictors of bone mass in a young cohort
CLINICAL JOURNAL OF SPORT MEDICINE
1998; 8 (3): 201-208
To compare the association of two measures of physical activity with bone mass in healthy children and young adults, as part of a larger study on bone mineral acquisition in youth.Cross-sectional observation study.General community, outpatient study.Subjects included 103 non-Hispanic white female (n = 54) and male (n = 49) healthy volunteers aged 9 to 25 years.Self-reported physical activity was measured by a 3-day activity diary of all activities and a questionnaire designed to capture recreational activities throughout the year. Activity was expressed as hours per week of weight-bearing and non-weight-bearing activity. Bone mass at the hip, spine, and whole body was measured by dual x-ray absorptiometry.The activity measures were not well correlated with each other. In males, weight-bearing and non-weight-bearing activity reported in 3-day diaries was positively associated with bone mass at the hip, spine, and whole body (p < 0.05). Among females, only weight-bearing activity measured by the yearly questionnaires was significantly positively associated with bone mass (p < 0.05). In males and females, weight-bearing activity was more highly correlated with bone mineral than was non-weight-bearing activity. In addition, the associations between activity and bone mass varied by skeletal site.The association between physical activity and bone mass varied both in direction and in significance depending on the physical activity instrument used. Gender differences were observed in the associations between specific activity instruments, type of activity (weight-bearing and non-weight-bearing), and bone mass at different skeletal sites. Variability associated with the two physical activity measures may contribute to discrepant findings in this study and in the literature.
View details for Web of Science ID 000078968600007
View details for PubMedID 9762479
Bone acquisition and loss in children and adults with cystic fibrosis: A longitudinal study
JOURNAL OF PEDIATRICS
1998; 133 (1): 18-27
To determine patterns of bone mineral acquisition in children and young adults with cystic fibrosis (CF) and to identify clinical and laboratory correlates of change in bone mineral density (BMD).Bone mineral and clinical status were assessed in 41 patients with CF (26 female, aged 9 to 50 years) at baseline and 1.5 years later. Bone mineral content of the lumber spine, femoral neck, and whole body was determined by dual-energy x-ray absorptiometry and expressed as BMD and bone mineral apparent density (BMAD). Changes in weight, height, pubertal status, glucocorticoid use, physical activity, disease severity, and biochemical markers of bone turnover were examined for associations with changes BMD and BMAD.Mean BMD Z-scores (adjusted for age and sex) were reduced at the spine, hip, and whole body at baseline in both adults and youths, and decreased further at all sites among youths at follow-up (-0.4 at spine, p < 0.05; -0.3 at hip, p < 0.10; -0.5 for whole body, p < 0.0005). These data indicate failure to gain bone mineral at the expected rate. BMAD was also reduced at follow-up, suggesting that the observed osteopenia could not be explained by small bone size. Bone loss at multiple sites was observed in four youths and two adults. In general glucocorticoid use, change in body mass, physical activity, and disease severity were the most significant correlates for change in BMD and in BMD Z-score.Osteopenia in CF generally reflects inadequate gains in bone mineral, although bone loss may occur, particularly in patients requiring glucoc therapy. Late gains in bone mineral may accompany weight gain and pubertal development, but the catch-up appears to be incomplete.
View details for Web of Science ID 000074728700006
View details for PubMedID 9672505
Bone mass and hip axis length in healthy Asian, black, Hispanic, and white American youths
JOURNAL OF BONE AND MINERAL RESEARCH
1997; 12 (11): 1922-1935
The primary objective of this study was to examine the associations of ethnicity, diet (calcium, protein, energy), and weight-bearing activity with dual-energy X-ray absorptiometry (DXA)-measured bone mass and hip axis length (HAL) in 423 Asians, blacks, Hispanics, and non-Hispanic Caucasians, aged 9-25 years. Bone mass was expressed as bone mineral content (BMC), bone mineral density (BMD), and bone mineral apparent density (BMAD). The data were analyzed using multiple linear regression, after stratifying for gender and pubertal stage and adjusting for height and weight. With few exceptions, Asians and Hispanics had comparable bone mass to whites at all pubertal stages. Greater femoral neck BMAD in black than white females was observed at all pubertal stages. Black males displayed greater BMD and BMAD than white males at all sites in early puberty and at the femoral neck in maturity. Calcium was positively and protein negatively related to BMAD at the femoral neck in early pubertal females. Among males, calcium was negatively associated with whole body BMC and BMD and spine BMD and BMAD in midpuberty. Weight-bearing activity was not associated with bone mass in females; in males, it was positively related only to femoral neck BMC in early puberty. There was an absence of evidence for ethnic differences in HAL among females. In males, we observed shorter HAL in mature Asians and blacks than whites. Neither diet nor activity was associated with HAL.
View details for Web of Science ID A1997YE19400019
View details for PubMedID 9383697
- Intakes of nutrients and foods relevant to bone health in ethnically diverse youths JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION 1997; 97 (9): 1010-1013
Determinants of femoral neck structure during adolescence.
AMER SOC BONE & MINERAL RES. 1997: T603–T603
View details for Web of Science ID A1997XP62700596
- Velocardiofacial syndrome presenting as hypocalcemia in early adolescence ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE 1997; 151 (7): 745-747
Correspondence between theoretical models and dual energy x-ray absorptiometry measurements of femoral cross-sectional growth during adolescence
JOURNAL OF ORTHOPAEDIC RESEARCH
1997; 15 (3): 473-476
We have developed an analytical model of long bone cross-sectional ontogeny in which appositional growth of the diaphysis is primarily driven by mechanical stimuli associated with increasing body mass during growth and development. In this study, our goal was to compare theoretical predictions of femoral diaphyseal structure from this model with measurements of femoral bone mineral and geometry by dual energy x-ray absorptiometry. Measurements of mid-diaphyseal femoral geometry and structure were made previously in 101 Caucasian adolescents and young adults 9-26 years of age. The data on measured bone mineral content and calculated section modulus were compared with the results of our analytical model of cross-sectional development of the human femur over the same age range. Both bone mineral content and section modulus showed good correspondence with experimental measurements when the relationships with age and body mass were examined. Strong linear relationships were evident for both parameters when examined as a function of body mass.
View details for Web of Science ID A1997XN54600022
View details for PubMedID 9246096
Body mass is the primary determinant of midfemoral bone acquisition during adolescent growth
1996; 19 (5): 519-526
To study the determinants of bone mass and structure during adolescence, we analyzed the femoral mid-diaphysis of 375 healthy adolescents and young adults, ages 9-26 years, from four ethnic cohorts (African-American, Asian-American, Caucasian, and Hispanic). Whole-body dual-energy X-ray absorptiometry (DXA) scans were used to determine diaphyseal length and mid-diaphyseal diameter of the left femur, as well as linear bone mineral content (BMCL) of a region at the mid-diaphysis. Cross-sectional geometric properties were estimated and used to calculate two structural strength indicators: the section modulus and the whole bone strength index. When the relationships between the bone measurements and age, pubertal group, height, or body mass were evaluated, all cross-sectional femoral measures correlated most strongly with body mass. Multiple regressions accounting for gender and ethnicity provided little additional predictive value over the simple regressions with body mass alone. Furthermore, accounting for all developmental parameters (age, pubertal group, body mass, lean body mass, calcium intake, physical activity level) as well as ethnicity and gender in a single saturated model also did not generally significantly improve the predictive results achieved using only body mass. Our results indicate that increases in midfemoral bone mass and cross-sectional properties during adolescence are primarily related to increases in mechanical loading as reflected by body mass.
View details for Web of Science ID A1996VR34700014
View details for PubMedID 8922652
Differences in bone mineral in young Asian and Caucasian Americans may reflect differences in bone size
JOURNAL OF BONE AND MINERAL RESEARCH
1996; 11 (10): 1545-1556
Bone mineral content (BMC) and areal bone mineral density (BMD) have been reported to be lower in Asian than in Caucasian adults. To determine if racial differences in bone mass are present in younger subjects and whether they reflect differences in estimated volumetric bone density or in bone size, we compared measurements of bone mineral in healthy young Asian- and Caucasian-American males and females. Bone mineral was measured at the lumbar spine (L2-L4), femoral neck (FN), and whole body (WB) by dual-energy X-ray absorptiometry (DXA) in 99 Asians (49 females, 50 males) and 103 Caucasians (54 females, 49 males) ages 9-26 years. Results were expressed as BMC, BMD, and apparent density (BMAD), an estimate of volumetric bone density that reduces the effect of bone size. Subjects were compared on the basis of chronological age as well as by Tanner stage to correct for potential differences in the timing of puberty. Habitual dietary intake and physical activity were also assessed and correlated with bone mineral. The Asian and Caucasian cohorts differed in body size, diet, and physical activity. Asian females were shorter than the Caucasian females at all stages of puberty and weighed less at pre-/early puberty (p < 0.05). Asian males were older than Caucasians at midpuberty (p < 0.01) and weighed less than the Caucasian males at pubertal maturity (p = 0.001). Asian youths also consumed less calcium and reported less weight-bearing activity. Racial differences were most apparent when comparing BMC data. Asian males had greater spine BMC at midpuberty and lower WB BMC at maturity (p < 0.05). Asian females had lower FN BMC through midpuberty and lower WB BMC in pre-/early puberty (p < 0.05). WB BMD and WB BMC/height values were significantly lower in mature Asian versus Caucasian males. No significant racial differences in BMAD were observed. Multivariate regression analysis indicated that the differences in BMD and BMAD between Asian and Caucasian subjects were largely attributable to differences in weight and pubertal stage, and, at the FN, in weight-bearing activity. Further, the explanatory variables were less strongly associated with BMAD than with BMD. In summary, no significant differences in BMD were found between Asian and Caucasian youths through midpuberty; however, WB BMD and WB BMC/height values were lower in Asian males at sexual maturity. We conclude that observed differences in bone mineral between Asians and Caucasians may be partially attributed to the smaller bone size of Asians.
View details for Web of Science ID A1996VK50000022
View details for PubMedID 8889856
Determinants of femoral geometry and structure during adolescent growth
JOURNAL OF ORTHOPAEDIC RESEARCH
1996; 14 (1): 22-29
Our goal was to understand developmental determinants of femoral structure during growth and sexual maturation by relating femoral measurements to gender and developmental factors (age, pubertal stage, height, and body mass). The bone mineral content of the femur was measured by dual energy x-ray absorptiometry in 101 healthy Caucasian adolescents and young adults, 9-26 years of age. After some simplifying assumptions had been made, cross-sectional geometric properties of the femoral midshaft were estimated. Two geometry-based structural indicators, the section modulus and whole bone strength index, were calculated to assess the structural characteristics of the femur. Femoral strength, as described by these structural indicators, increased dramatically from childhood through young adulthood. Regressions were performed between these femoral measurements and the developmental factors. Our data show that of age, pubertal stage, body mass, and height, body mass is the strongest predictor of femoral cross-sectional properties, and the correlation of body mass with femoral cross-sectional structure is independent of gender. A model including all four developmental factors and gender did not substantially increase the accuracy of predictions compared with the model with body mass alone. In light of previous research, we hypothesize that body mass is an indicator of in vivo loading and that this in vivo loading influences the cross-sectional growth of the long bones.
View details for Web of Science ID A1996UA58800005
View details for PubMedID 8618162
Validity of the body mass index as an indicator of adiposity in an ethnically diverse population of youths
AMERICAN JOURNAL OF HUMAN BIOLOGY
1996; 8 (5): 641-651
View details for Web of Science ID A1996VP96200009
Correlates of osteopenia in patients with cystic fibrosis
1996; 97 (1): 103-111
As the expected survival improves for individuals with cystic fibrosis, these individuals face myriad medical complications. The goals of this study were to examine the prevalence of osteopenia in children and adults with cystic fibrosis and to elucidate the risk factors associated with deficits in bone mineral.We compared bone mineral levels in 49 patients (30 female and 19 male) ages 8 through 48 years with those of age- and sex-matched control subjects. Lumbar spine, femoral neck, and whole-body bone mineral were measured by dual-energy radiographic absorptiometry and expressed in terms of bone mineral content, areal bone density (BMD), and bone mineral apparent density (BMAD), which corrects for differences in bone size. Clinical variables were evaluated as potential correlates of bone mineral.Patients with cystic fibrosis had significantly less bone mineral than did control subjects at all sites using all expressions of bone mass. Mean BMD z scores were -1.7 (lumbar spine), -1.9 (femoral neck), and -1.2 (whole body). BMAD z scores also were significantly low for age and gender. Twenty-six of the 49 patients (8 adolescents) had significant osteopenia according to their BMD z scores; 14 of the 45 patients (5 adolescents) with available BMAD z scores had significantly low values at one or more sites. Age, pubertal stage, body mass, caloric expenditure, illness severity, glucocorticoid therapy, and gonadal function predicted bone mineral status. Serum parathyroid hormone and calcium, carbohydrate intake, and weight-bearing activity had limited predictive value. Daily calcium intake and cystic fibrosis transmembrane regulator genotype did not predict bone mineral status.Osteopenia is common at all ages in cystic fibrosis, suggesting that inadequate bone mineral accretion as well as increased bone loss contribute to the deficits in bone mineral observed. Several clinical factors seem to contribute to these deficits.
View details for Web of Science ID A1996TQ42400019
View details for PubMedID 8545201
BONE-MINERAL DENSITY DURING TREATMENT OF CENTRAL PRECOCIOUS PUBERTY
JOURNAL OF PEDIATRICS
1995; 127 (5): 819-822
Treatment of adults with gonadotropin releasing hormone analogs has resulted in rapid loss in bone mineral density (BMD). We measured lumbar and femoral neck BMD by dual-energy x-ray absorptiometry during 2 years of depot leuprolide therapy in 13 girls (mean age, 7.5 years; mean bone age, 10.9 years). At baseline, BMD was elevated for age and concordant with the advanced skeletal age. During therapy with gonadotropin releasing hormone analog, BMD values increased and BMD standard deviation scores for age and skeletal age did not change.
View details for Web of Science ID A1995TD93100031
View details for PubMedID 7472845
THE BONE-MINERAL STATUS OF PATIENTS WITH MARFAN-SYNDROME
JOURNAL OF BONE AND MINERAL RESEARCH
1995; 10 (10): 1550-1555
Osteopenia at the hip and low total body calcium content have been reported in women with Marfan syndrome. Using dual X-ray absorptiometry (DXA), we evaluated the lumbar spine L2-L4 and proximal femur bone mineral density (BMD,/cm2) in 32 women and 16 children with Marfan syndrome. The women were 38 +/- 10 (SD) years old (23-58 years); their mean height was 178.7 +/- 8 cm. The children (9 boys and girls were 9.9-17.5 years old. Children were tall for their ages but of normal weight. All subjects were moderately active, without previous nontraumatic fracture. In the women, BMD was reduced at L2-L4, femoral neck (fnk), trochanter (tr), and intertrochanter (intr) (p < 0.0001-0.006), compared with age-predicted values. Z scores for L2-L4 and for the fnk, tr, and intr, were -0.59 +/- 1.06,-1.25 +/- 0.99,-1.03 +/- 0.91, respectively. The average hip axis length (HAL) of 11.5 +/- 0.093 cm was at the 80th percentile for women. No significant change was observed in 1 year follow-up BMD measurements in 13 women (fnk = -0.23 +/- 2.3%/year; L2-L4 = -0.43 +/- 1.57%/year). In Marfan children, BMD correlated with age, height, and pubertal development. Femoral neck BMG was reduced (Z = -0.74 +/- 1.22,p < 0.05) with a nonsignificant trend toward decreased BMD at L2-L4 (Z = 33 +/- 1.48). Resorption markers in Marfan women were normal and did not correlate with bone status. We conclude that women with Marfan syndrome have both axial and peripheral osteopenia as well as an increased HAL. This combination of findings likely increases substantially their long-term risk for hip fracture. Presence of osteopenia in Marfan children indicates that the skeletal deficits of Marfan syndrome may reflect inadequate bone acquisition.
View details for Web of Science ID A1995RX78000016
View details for PubMedID 8686512
A PHYSICIAN SURVEY OF THERAPY FOR EXERCISE-ASSOCIATED AMENORRHEA - A BRIEF REPORT
CLINICAL JOURNAL OF SPORT MEDICINE
1995; 5 (4): 246-250
Amenorrheic athletes face an increased risk of osteopenia and stress fractures. Optimal treatment for exercise-associated amenorrhea remains controversial, reflecting limited data on the therapeutic effects of hormonal or nutritional intervention in the prevention of osteopenia. To determine physician opinions regarding preferred management of amenorrheic athletes, members of the American Medical Society for Sports Medicine (AMSSM) were surveyed by questionnaire. Practitioners were asked if they prescribed sex steroid replacement, calcium supplementation, weight gain, or decreased physical activity for amenorrheic athletes. The 159 respondents included predominantly sports medicine (56%) and family medicine (32%) physicians. Sex steroid replacement was endorsed by 92%, calcium supplementation by 87%, increased caloric intake by 64%, decreased exercise intensity by 57%, weight gain by 43%, and vitamin supplementation by 26%. These findings suggest that sex steroids are used commonly to treat amenorrheic athletes, despite the paucity of data demonstrating their efficacy in preserving bone mass in this disorder. Further research is needed to define the benefits of estrogen alone or in combination with nutritional intervention for preserving bone mass in female athletes.
View details for Web of Science ID A1995RW78300006
View details for PubMedID 7496850
LOADING FROM BODY-MASS DETERMINES BONE MASS AND STRUCTURE DURING ADOLESCENCE
WILEY-BLACKWELL. 1995: S235–S235
View details for Web of Science ID A1995RN48400385
Osteopenia in Turner girls
4th International Symposium on Turner Syndrome
ELSEVIER SCIENCE PUBL B V. 1995: 233–240
View details for Web of Science ID A1995BE78L00033
OCCULT CELIAC-DISEASE - NOT A CAUSE OF SHORT STATURE
NATURE PUBLISHING GROUP. 1994: A109–A109
View details for Web of Science ID A1994NG77900636
BODY CHANGES IN ADOLESCENT PATIENTS WITH GROWTH-HORMONE RECEPTOR DEFICIENCY RECEIVING RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I AND LUTEINIZING-HORMONE-RELEASING HORMONE ANALOG - PRELIMINARY-RESULTS
2nd International Workshop on Growth Hormone Insensitivity
WILEY-BLACKWELL PUBLISHING, INC. 1994: 133–136
View details for Web of Science ID A1994PC97600023
COMPARISON OF A RAPID, SINGLE-SAMPLE SUBCUTANEOUS GNRH STIMULATION TEST WITH STANDARD-IV GNRH TESTING IN THE EVALUATION OF PRECOCIOUS PUBERTY
NATURE PUBLISHING GROUP. 1994: A98–A98
View details for Web of Science ID A1994NG77900572
A PROSPECTIVE RANDOMIZED TRIAL OF GROWTH-RESPONSE TO 2 DOSAGES OF RHGH
NATURE PUBLISHING GROUP. 1994: A93–A93
View details for Web of Science ID A1994NG77900545
OSTEOPENIA IN ADULTS WITH CYSTIC-FIBROSIS
AMERICAN JOURNAL OF MEDICINE
1994; 96 (1): 27-34
To examine the frequency and severity of osteopenia in adults with cystic fibrosis and the clinical variables associated with reduced bone mineral.The bone mineral status of 22 white adults (14 women) with cystic fibrosis was compared with normative data from healthy white control subjects in a university medical center. Lumbar spine, femoral neck, and whole-body bone mineral was determined by dual energy x-ray absorptiometry and expressed as bone mineral content (g), bone mineral density (g/cm2), and bone mineral apparent density (g/cm3). Bone mass was related to age, body mass, gonadal function, pulmonary status, and glucocorticoid exposure to identify variables associated with reduced bone mineral in cystic fibrosis.Bone mineral in adults with cystic fibrosis was significantly below expected values for age and sex at all sites using all expressions of bone mass. The mean Z-score was -2.8 for the lumbar spine bone density, -2.5 for the femoral neck, and -2.0 for the whole body. Bone mineral apparent density (a term that minimizes the influence of bone dimensions) was also significantly reduced in patients at the lumbar spine (p < 0.0001) and femoral neck (p < 0.001 to p < 0.0001), indicating that the bone mineral deficit seen in adults with cystic fibrosis could not be attributed to differences in bone size. Age, weight, height, and body mass index were significantly correlated with bone mineral. Pulmonary status, glucocorticoid use, and gonadal function failed to predict bone mineral status.Osteopenia and osteoporosis occur commonly in young adults with cystic fibrosis. Age and body mass are predictive of bone mineral, although the pathogenesis of this bone mineral deficit is likely multifactorial.
View details for Web of Science ID A1994MU31300006
View details for PubMedID 8304359
LOW BONE-MINERAL DENSITY AT AXIAL AND APPENDICULAR SITES IN AMENORRHEIC ATHLETES
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
1993; 25 (11): 1197-1202
Amenorrheic athletes have low axial bone-mineral density (BMD, g.cm-2). We compared 12 amenorrheic and 9 eumenorrheic women athletes to determine whether athletes with amenorrhea have lower BMD in other skeletal regions, including weight-bearing lower limbs. BMD was measured by dual energy x-ray and single photon absorptiometry. Both groups had similar age, body mass, and exercise quantity. Women with amenorrhea missed 86.3 +/- 58.3 menstrual periods since menarche. BMD was lower in the amenorrheic vs eumenorrheic subjects for the lumbar spine (0.928 +/- 0.056 vs 1.050 +/- 0.110, P < 0.005), whole body (1.032 +/- 0.05 vs 1.09 +/- 0.06, P < 0.05), most regions of the whole body (P < 0.05-0.001), all areas of the proximal femur (P < 0.005), and at the femoral mid-shaft (1.333 +/- 0.109 vs 1.491 +/- 0.088, P < 0.005). No significant differences were detected at the mid-radius and tibial shaft. The best predictors of BMD were years of regular menstruation for lumbar spine; and years of amenorrhea for hip, femoral mid-shaft, and whole body. We conclude that low BMD in athletes with amenorrhea is not limited to the axial skeleton but is also present in other regions including appendicular weight-bearing bones.
View details for Web of Science ID A1993MF56400001
View details for PubMedID 8289605
TURNER SYNDROME ADOLESCENTS RECEIVING GROWTH-HORMONE ARE NOT OSTEOPENIC
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
1993; 76 (4): 861-866
Deficits in bone mineral have been widely reported in Turner syndrome. The bone mineral status of 19 adolescents with Turner syndrome (16 receiving GH therapy) was evaluated by dual photon absorptiometry of the lumbar spine and whole body and compared with a normal female control group (n = 45) with the same mean age (14.3 yr). The conventional measurements of bone mass, bone mineral content (BMC = g), and bone mineral density (BMD = g/cm2), as well as bone mineral apparent density (BMAD = g/cm3), an expression of bone mineral adjusted for bone volume, were determined for both sites. Although mean BMC was decreased in Turner females, mean BMD and BMAD in the two groups were not significantly different. Analyzed in relation to chronologic age, bone age, height, and pubertal status, mean BMD and BMAD values in Turner subjects were equal to or greater than that of controls. BMD and BMAD were elevated in the Turner group vs. controls matched for height. In subjects with bone age less than or equal to 12.5 yr, mean spinal BMAD was unexpectedly greater in Turner patients compared with controls (0.148 +/- 0.011 vs. 0.134 +/- 0.013, P = 0.009). When data were analyzed by pubertal status, mean spinal BMD and BMAD in subjects with Tanner breast stages 1-2 were higher in the Turner group than in the controls (BMAD 0.146 +/- 0.011 vs. 0.132 +/- 0.015, P = 0.015). No differences were seen in mid- to late pubertal females. Bone mineral properties were additionally reassessed after a mean interval of 1.3 yr in 10 of the subjects with Turner syndrome. Percentage increases in mean follow-up spinal BMD and BMAD were greater in 5 subjects begun on estrogen replacement than in 5 untreated patients. We conclude that: 1) bone mineral values in adolescents with Turner syndrome on GH therapy are not abnormal, 2) lumbar bone mineral is greater in younger Turner adolescents matched with controls for bone age or pubertal status, a difference which could relate to GH therapy, and 3) estrogen therapy may augment bone mineral accretion in Turner syndrome, but early estrogen replacement cannot be justified on the basis of bone mineral status.
View details for Web of Science ID A1993KW77300012
View details for PubMedID 8473397
2-YEAR RESULTS OF TREATMENT WITH DEPOT LEUPROLIDE ACETATE FOR CENTRAL PRECOCIOUS PUBERTY
JOURNAL OF PEDIATRICS
1992; 121 (4): 634-640
We report results from 2 years of therapy with the long-acting form of the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate, which was previously reported in short-term trials to be efficacious in the treatment of central precocious puberty. Thirteen girls and two boys, aged 1.9 to 9.7 years, who satisfied clinical criteria including GnRH-stimulated luteinizing hormone (LH) greater than 10 IU/L (mean radioimmunoassay LH, 29.1 +/- 5.54 IU/L), received depot leuprolide, 6 to 15 mg intramuscularly every 4 weeks. Estradiol (or testosterone), insulin-like growth factor I, and GnRH-stimulated gonadotropins were obtained at baseline, at 2 months, and at 6-month intervals with bone age determinations. Pubertal progression ceased in all patients, and menses did not occur. Mean increase in height during therapy was 5.77 +/- 2.0 cm/yr. Predicted adult height increased over baseline by 5.52 +/- 1.16 cm at 18 months. Mean estradiol values in the girls declined from 3.3 +/- 0.6 to 0.60 +/- 0.03 ng/dl, with no overlap of baseline and treatment values. The mean basal LH value was unchanged by therapy; mean basal and peak LH values for all follow-up GnRH stimulation tests were 4.05 +/- 0.57 and 4.95 +/- 0.70 IU/L, respectively. Basal and peak follicle-stimulating hormone (FSH) values were suppressed from 4.10 +/- 0.62 and 10.06 +/- 1.34 IU/L, respectively, to generally undetectable levels (< 1). Comparison with untreated control patients suggested that basal LH did not completely return to prepubertal levels, whereas FSH levels were suppressed below prepubertal levels. Estradiol, FSH, and LH levels reached their nadir by 2 months; in contrast, mean serum levels of insulin-like growth factor I progressively declined from +0.57 +/- 0.19 SD score to -0.06 +/- 0.22 SD score at 24 months. Two girls were withdrawn from the study because of reactions at injection sites, with apparent sterile abscess formation in one patient. This study provides evidence that (1) long-term treatment with depot leuprolide is characterized by immediate and sustained laboratory and clinical suppression, (2) GnRH-stimulated LH and random FSH and estradiol concentrations are useful laboratory measures of efficacy, and (3) the progressive increase in predicted adult height is temporally associated with decreased serum levels of insulin-like growth factor I and striking deceleration of bone age advancement.
View details for Web of Science ID A1992JR92000026
View details for PubMedID 1403402
OSTEOPOROSIS IN YOUNG-ADULTS WITH CYSTIC-FIBROSIS
AMER SOC BONE & MINERAL RES. 1992: S183–S183
View details for Web of Science ID A1992JL59500361
CLINICAL AND ANTHROPOMETRIC CORRELATES OF BONE-MINERAL ACQUISITION IN HEALTHY ADOLESCENT GIRLS
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
1991; 73 (6): 1332-1339
We studied the acquisition of bone mineral in 45 healthy prepubertal and pubertal girls and related changes in bone mass to age, body mass, pubertal status, calcium intake, and exercise. A subgroup of 12 girls was followed longitudinally. Bone mineral content (BMC) of the lumbar spine, whole body, and femoral neck was measured by dual energy x-ray absorptiometry and that at the midradius by single photon absorptiometry. For comparison, spine and whole body mineral contents were also measured by dual photon absorptiometry. Bone mass was expressed in conventional terms of BMC and area density (BMD). However, we show that BMD fails to account for differences in bone thickness. Since bone size increases during adolescence, we present a new expression, bone mineral apparent density (BMAD), which is BMC normalized to a derived bone reference volume. This term minimizes the effect of bone geometry and allows comparisons of mineral status among bones of similar shape but different size. BMC increased with age at all sites. These increases were most rapid in the early teens and plateaued after 16 yr of age. When bone mineral values at all sites were regressed against age, height, weight, or pubertal stage, consistent relationships emerged, in which BMC was most strongly correlated, BMD was correlated to an intermediate degree, and BMAD correlated only modestly or without significance. Dietary calcium and exercise level did not correlate significantly with bone mass. From these relationships, we attribute 50% of the pubertal increase in spine mineral and 99% of the change in whole body mineral to bone expansion rather than to an increase in bone mineral per unit volume. In multiple regressions, pubertal stage most consistently predicted mineral status. This study emphasizes the importance of pubertal development and body size as determinants of bone acquisition in girls. BMAD may prove to be particularly useful in studies of bone acquisition during periods of rapid skeletal growth.
View details for Web of Science ID A1991GW87900028
View details for PubMedID 1955516
EFFICACY OF DEPOT LEUPROLIDE ACETATE IN THE TREATMENT OF CENTRAL PRECOCIOUS PUBERTY
NATURE PUBLISHING GROUP. 1991: A83–A83
View details for Web of Science ID A1991FE03800480
RECOVERY FROM OSTEOPENIA IN ADOLESCENT GIRLS WITH ANOREXIA-NERVOSA
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
1991; 72 (3): 602-606
Osteopenia is a frequent complication of anorexia nervosa (AN). To determine whether the deficit in bone mineral changes during the course of this illness, we studied 15 adolescent patients prospectively for 12-16 months using dual photon absorptiometry of the spine and whole body. At follow-up, mean weight, height, and body mass index (BMI) had increased significantly, although 6 girls had further weight loss or minimal gain (less than 1.2 kg). Spontaneous menses occurred in 2 girls, and 3 others were given estrogen replacement. Bone mineral density of the lumbar spine did not change significantly (mean +/- SD, 0.836 +/- 0.137 vs. 0.855 +/- 0.096 g/cm2), while whole body bone mineral density increased (0.710 +/- 0.118 vs. 0.773 +/- 0.105; P less than 0.05). Despite gains in bone mineral, 8 patients had osteopenia of the spine and/or whole body. Changes in weight, height, and BMI were significant predictors of change in bone mineral density. Increased bone mass occurred with weight gain before return of menses; conversely, weight loss was associated with further decreases in bone density. In 1 patient who failed to gain weight, estrogen therapy resulted in increased spinal, but not whole body, bone mineral. We also studied a second group of 9 women who had recovered from AN during adolescence. All 9 had normal whole body bone mineral for age, but 3 had osteopenia of the lumbar spine. We conclude that osteopenia in adolescents with AN reflects bone loss, perhaps combined with decreased bone accretion. Weight rehabilitation results in increased bone mineral before the return of menses. Estrogen may have an independent effect on bone mass. The persistence of osteopenia after recovery indicates that deficits in bone mineral acquired during adolescence may not be completely reversible.
View details for Web of Science ID A1991FA52300012
View details for PubMedID 1997514
Thyrotropin inhibits while insulin, epidermal growth factor and tetradecanoyl phorbol acetate stimulate insulin-like growth factor binding protein secretion from sheep thyroid cells.
1991; 4 (3): 221-230
Six insulin-like growth factor binding proteins (IGFBP) have been identified in the conditioned medium from sheep thyroid cells cultured under serum-free conditions. IGFBPs of 32, 28, 23 and 19 kDa were secreted by cells cultured for 14 days in serum-free and hormone-free medium. The constitutive secretion of IGFBP was inhibited by thyrotropin (TSH, 0.3 mU per mL). The effect was most marked on the secretion of the 28 kDa BP. High insulin concentrations stimulated the secretion of this IGFBP. The stimulatory effects of insulin were inhibited by TSH. Growth hormone treatment decreased the secretion of the 28 kDa protein. Tetradecanoylphorbol-13 acetate (TPA) and epidermal growth factor (EGF) both of which stimulate thyroid cell growth but inhibit differentiated function, markedly stimulated IGFBP secretion and induced the appearance of a 46 and a 150 kDa IGFBP. The effects of EGF and TPA were not identical. A rat IGFBP-2 cDNA reacted with sheep thyroid RNA of approximate size 1.6 kb. TPA treatment increased IGFBP-2 mRNA. Other hormones used to enhance differentiation and growth in thyroid cells in culture i.e. transferrin, somatostatin, cortisol and glycyl-histidyl-lysine acetate had no marked effects on IGFBP secretion nor on TSH-dependent, insulin-mediated iodide uptake and organification and cell growth. We show a correlation between secretion of high molecular weight IGFBP with enhanced growth but decreased function. Conversely, we find a correlation between decreased secretion of the 28 kDa BP and increased growth and function.
View details for PubMedID 1722684
DECREASED BONE-DENSITY IN ADOLESCENT GIRLS WITH ANOREXIA-NERVOSA
1990; 86 (3): 440-447
Osteoporosis develops in women with chronic anorexia nervosa. To determine whether bone mass is reduced in younger patients as well, bone density was studied in a group of adolescent patients with anorexia nervosa. With single- and dual-photon absorptiometry, a comparison was made of bone mineral density of midradius, lumbar spine, and whole body in 18 girls (12 to 20 years of age) with anorexia nervosa and 25 healthy control subjects of comparable age. Patients had significantly lower lumbar vertebral bone density than did control subjects (0.830 +/- 0.140 vs 1.054 +/- 0.139 g/cm2) and significantly lower whole body bone mass (0.700 +/- 0.130 vs 0.955 +/- 0.130 g/cm2). Midradius bone density was not significantly reduced. Of 18 patients, 12 had bone density greater than 2 standard deviations less than normal values for age. The diagnosis of anorexia nervosa had been made less than 1 year earlier for half of these girls. Body mass index correlated significantly with bone mass in girls who were not anorexic (P less than .05, .005, and .0001 for lumbar, radius, and whole body, respectively). Bone mineral correlated significantly with body mass index in patients with anorexia nervosa as well. In addition, age at onset and duration of anorexia nervosa, but not calcium intake, activity level, or duration of amenorrhea correlated significantly with bone mineral density. It was concluded that important deficits of bone mass occur as a frequent and often early complication of anorexia nervosa in adolescence. Whole body is considerably more sensitive than midradius bone density as a measure of cortical bone loss in this illness.(ABSTRACT TRUNCATED AT 250 WORDS)
View details for Web of Science ID A1990DW64600018
View details for PubMedID 2388792
EFFECT OF ESTROGEN ON GROWTH-HORMONE CONCENTRATIONS FOLLOWING STIMULATION WITH CLONIDINE
NATURE PUBLISHING GROUP. 1990: A88–A88
View details for Web of Science ID A1990CW36200512
LONG-ACTING LUTEINIZING RELEASING-FACTOR (LRF) ANALOG FOR CENTRAL PRECOCIOUS PUBERTY
NATURE PUBLISHING GROUP. 1990: A82–A82
View details for Web of Science ID A1990CW36200473
Interaction of TSH, insulin and insulin-like growth factors in regulating thyroid growth and function.
1990; 2 (2-3): 99-109
Primary cultures of sheep thyroid cells have been used to study regulation of thyroid growth and function by growth factors and TSH. Cells were plated at low density to minimize contributions from the endogenously produced insulin-like growth factors and their binding proteins and other proteins or hormones secreted by thyroid cells in culture. Growth of the cells was followed for 7-11 days in medium without serum. We found that TSH by itself was unable to stimulate thyroid growth. However, the ability of insulin and IGF-I to stimulate thyroid cell growth was markedly potentiated by TSH. Thyroid function was assayed by measurement of uptake of pertechnetate and organification of iodide and also by synthesis of thyroglobulin mRNA. TSH alone was unable to stimulate thyroid function appreciably. Insulin and IGF-I were ineffective by themselves at stimulating thyroid differentiated function, but in the presence of TSH, all indices were stimulated markedly. We conclude that TSH by itself is not a growth factor for thyroid cells. However, in the presence of insulin or IGF-I, TSH potentiates the growth-stimulating properties of this hormone. Similarly, TSH by itself does not stimulate thyroid function but requires the presence of insulin or IGF-I. These data show the cooperative interactions between growth factors and TSH in regulating both thyroid growth and function.
View details for PubMedID 2160262
INDUCTION OF ORNITHINE DECARBOXYLASE ACTIVITY BY GROWTH AND DIFFERENTIATION FACTORS IN FRTL-5 CELLS
YALE JOURNAL OF BIOLOGY AND MEDICINE
1989; 62 (5): 435-444
Induction of ornithine decarboxylase has been correlated with the onset of cellular proliferation and cAMP production. Whether the resulting increases in polyamine levels are essential mediators of growth and/or differentiation or are merely incidental remains controversial. We have used FRTL-5 thyroid cells in culture to study the effects of three growth factors on ornithine decarboxylase activity. These factors [TSH, bovine calf serum, and 12-O-tetradecanoylphorbol-13-acetate (TPA)] are thought to act through different intracellular pathways. TSH stimulates cAMP production in thyroid cells, calf serum acts through ill-defined pathways to stimulate growth, and TPA is known to activate protein kinase C. Bovine calf serum and TSH acted synergistically to induce ornithine decarboxylase activity. Activity was maximal when the phosphodiesterase inhibitor, methyl isobutyl xanthine, was included. Individually, neither serum nor TSH was a potent stimulator of the enzyme. Ornithine decarboxylase mRNA was apparent on Northern blots as a doublet following one hour of exposure to these agents. TPA did not stimulate ornithine decarboxylase activity and had an inhibitory effect on enzyme induction by TSH and serum. Difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, inhibited growth induced by both TPA and TSH in putrescine-free medium. This effect was not apparent in medium containing 10(-5) M putrescine. The data indicate that, although intracellular levels of cyclic AMP regulate ornithine decarboxylase activity, a component in serum is necessary for significant induction of this enzyme. Factors stimulating growth by non-cyclic AMP-dependent pathways may act without apparently stimulating this enzyme, although polyamines appear to be essential for their growth stimulatory effects.
View details for Web of Science ID A1989CP89400003
View details for PubMedID 2483473
REGULATION OF THYROPEROXIDASE, THYROGLOBULIN AND IODIDE LEVELS IN SHEEP THYROID-CELLS BY TSH, TUMOR PROMOTERS AND EPIDERMAL GROWTH-FACTOR
1989; 71 (2): 227-235
Using sheep thyroid cells in culture, we have studied the effects of thyroid stimulating hormone (TSH), epidermal growth factor (EGF) and the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) on the activity and expression of both thyroglobulin (Tg) and thyroid peroxidase (TPO) and on the ability of cells to trap and organify iodide. Using Western blotting techniques, we found that TSH increased the absolute cellular levels of Tg. The optimum TSH concentration for Tg mRNA production was between 0.1-1.0 mU/ml. Thyroglobulin mRNA levels were stimulated by TSH but detectable levels were also present in cultures grown in its absence containing cortisol, insulin, transferrin, somatostatin and glycyl-lysyl-histidyl acetate. Unlike Tg, TPO protein levels were found to be completely dependent upon TSH. A time course of TSH stimulation of TPO mRNA showed increases after 8 h of TSH stimulation, whereas induction of Tg mRNA by TSH was seen at 24 h. Iodide trapping and organification were also TSH-dependent processes, showing maximum activities at 300-500 muU/ml of TSH. The addition of 10 nM TPA caused a biphasic decrease in radiolabeled pertechnetate uptake, with complete inhibition being seen at 14 h. Inhibition of iodide organification occurred more rapidly. TPA and EGF (1 nM) reduced the amount of newly synthesized Tg in TSH-stimulated cells by 50% but the absolute amount of Tg within the cells was not markedly inhibited at these early times.(ABSTRACT TRUNCATED AT 250 WORDS)
View details for Web of Science ID A1989T845000005
View details for PubMedID 2495823
HYPOTHYROXINEMIA ASSOCIATED WITH PARADOXICAL HYPERTRIIODOTHYRONINEMIA IN CHILDREN WITH GRAVES-DISEASE TREATED WITH PROPYLTHIOURACIL
SLACK INC. 1988: A203–A203
View details for Web of Science ID A1988L516801183
- EFFECTS OF AMIODARONE DURING PREGNANCY CANADIAN MEDICAL ASSOCIATION JOURNAL 1987; 136 (9): 959-960
ENDOCRINE FUNCTION IN MALNOURISHED PATIENTS WITH CYSTIC-FIBROSIS (CF)
WILLIAMS & WILKINS. 1987: A499–A499
View details for Web of Science ID A1987G700501952
Role of non-TSH factors in thyroid cell growth.
Acta endocrinologica. Supplementum
1987; 281: 231-237
The effects of insulin, the tumour promotor tetradecanoyl phorbol acetate (TPA), TSH and combinations of these factors on growth and DNA synthesis have been examined in the FRTL-5 cell strain and in sheep thyroid cells. In addition the regulation of the production by sheep thyroid cells of the insulin-like growth factors (IGF) by TSH and their possible autocrine roles have been investigated. We found that insulin and the IGF's stimulated DNA synthesis in both rat FRTL-5 cells and sheep cells. TPA also stimulated growth in both cell types, and its effects were additive to those of insulin. In the FRTL-5 cells, TPA was a less potent stimulator of growth than TSH, but the effects of TPA and TSH were not additive which may imply growth stimulation through a common pathway. In sheep cells TSH was not mitogenic and did not appear to activate protein kinase C, the receptor for TPA. Sheep cells, unlike FRTL-5 cells, were found to produce IGF-I and IGF-II, and their syntheses were regulated by TSH. Sheep cells were also found to produce IGF-binding proteins which may modulate the biologic effects of the IGF's. Sheep thyroid IGF binding proteins were found to copurify with urokinase-like plasminogen activator on immunoaffinity chromatography. The production of this serine protease has also been shown to be regulated by TSH.
View details for PubMedID 3475906
ROLE OF NON-TSH FACTORS IN THYROID CELL-GROWTH
1987; 115: 231-237
View details for Web of Science ID A1987J547600041
DISPARATE UPTAKE OF (TCO4)-TC-99M AND I-125 IN THYROID-CELLS IN CULTURE
HORMONE AND METABOLIC RESEARCH
1986; 18 (3): 167-172
Pertechnetate (99mTcO4-) is a large anion that is thought to be trapped but not organified by the thyroid. In order to determine its usefulness in discriminating trapping from organification in thyroid cell culture, the uptake of 99mTcO4- has been compared to that of 125I- both in sheep thyroid cells and in FRTL5 cells, a functional rat thyroid cell line. We found that uptake of both isotopes was dependent on TSH or agents that raised intracellular cAMP levels and was displaceable with iodide in both cell types. However in rat cell line 99mTcO4- uptake was up to eight-fold higher than 125I- uptake, and 99mTcO4- but not 125I- uptake was doubled by methimazole treatment. A considerable proportion of 99mTcO4- but not 125I- taken up by the FRTL5 cell but not the sheep cells was precipitable with TCA. This proportion was increased by methimazole treatment. We also found marked differences in sensitivity to ouabain between the two cell types. These results illustrate the differences between species in 125I- and 99mTcO4- transport and support the concerns expressed by Socolow and Ingbar (1967) in using 99mTcO4- as a direct and precise indicator of iodide transport activity.
View details for Web of Science ID A1986A796200006
View details for PubMedID 3009293
PHORBOL ESTERS STIMULATE GROWTH AND INHIBIT DIFFERENTIATION IN CULTURED THYROID-CELLS
1985; 116 (4): 1603-1609
The potent tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) has biological effects on cell growth and differentiation similar to the effects of epidermal growth factor (EGF) on a variety of cells. Since EGF has been shown recently to stimulate thyroid cell proliferation and inhibit iodine metabolism, we examined the effects of phorbol esters on primary ovine thyroid cultures. TPA stimulated cell growth in a manner similar to EGF. The growth effects of EGF and TPA in combination were not additive. In contrast, TPA (1.6 X 10(-7) M) was a more potent inhibitor of iodine uptake and incorporation than EGF (10(-9) M) at their maximally effective concentrations. The inhibitory effects of TPA were also more rapid and less reversible than those of EGF. TPA and EGF in combination inhibited iodine metabolism more than either agent alone at its maximally effective concentration. Both TPA and EGF reduced the accumulation of cAMP in TSH-stimulated cells, but (Bu)2cAMP and stimulators of adenylate cyclase failed to overcome TPA's inhibition of iodine metabolism. TPA interacted with EGF by reducing the affinity of membrane receptors for [125I]iodo-EGF. Although the alteration in EGF-receptor interaction induced by TPA may play a role in mediating TPA's biological effects, the additive effects of TPA and EGF on iodine metabolism suggest that TPA does not act solely through the EGF receptor-effector system. Agents other than TSH, including phorbol esters and EGF, are potent modulators of thyroid growth and differentiated function. Despite several similarities in biological activity, TPA and EGF do not modulate differentiated function in an identical manner. Both factors act at least partially through a non-cAMP-dependent pathway, providing indirect evidence of another second messenger(s) in the control of thyroid function.
View details for Web of Science ID A1985AEG2300052
View details for PubMedID 2982592
THE EFFECTS OF GROWTH-FACTORS AND SERUM ON DNA-SYNTHESIS AND DIFFERENTIATION IN THYROID-CELLS IN CULTURE
MOLECULAR AND CELLULAR ENDOCRINOLOGY
1984; 38 (2-3): 141-150
The effects of three putative growth factors and serum on [Me-3H]thymidine and Na125I incorporation into thyroid cell cultures have been examined. We found that serum and EGF could stimulate radioactively labelled thymidine incorporation into confluent cultures. However, both factors completely inhibited iodine uptake and organification at low concentrations. Insulin also stimulated [Me-3H]thymidine incorporation but had no adverse effect on thyroid differentiated function. TSH examined under the same conditions was not a growth factor but was essential to maintain differentiated functions. We conclude that thyroid growth and differentiation are not mutually exclusive processes. However, EGF and serum inhibit thyroid differentiated function at very low concentrations. Elucidation of the physiological role of these factors and their mechanism of action may lead to a greater understanding of thyroid hormone biosynthesis.
View details for Web of Science ID A1984TY52500006
View details for PubMedID 6391978
TRANS-PLACENTAL EFFECTS OF 3,5-DIMETHYL-3'-ISOPROPYL-L-THYRONINE ON FETAL HYPOTHYROIDISM IN PRIMATES
1983; 112 (6): 2021-2024
Pregnant Rhesus monkeys treated with 131I at midgestation become hypothyroid and produce fetuses without demonstrable thyroid tissue. In an effort to prevent both maternal and fetal hypothyroidism, we treated 131I-treated pregnant monkeys with 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), a thyroid hormone analog with structural changes which facilitate placental transfer. Five pregnant monkeys were treated with 131I (mCi/kg) at 83-87 days of gestation. One week later, three monkeys were started on treatment with DIMIT (10 micrograms kg-1 day-1, im) and two on im L-T4 (2 micrograms kg-1 day-1). Treatment was continued until delivery by Caesarian section at 152-157 days of gestation. None of the DIMIT-treated mothers became clinically hypothyroid, nor did they have elevated serum TSH concentrations despite low serum levels of T3 and T4. T4-treated mothers were also maintained clinically and biochemically euthyroid. At delivery, infants of DIMIT-treated mothers had normal respiratory function and skeletal maturation. Basal and TRH-stimulated TSH concentrations were suppressed in two of the three infants. By contrast, both T4-treated infants resembled untreated cretinous newborns and died soon after delivery from respiratory failure. Serum TSH concentrations were elevated and skeletal maturation was markedly delayed in these animals. We conclude that DIMIT administration to 131I-treated monkeys prevents clinical and biochemical hypothyroidism in the mother and prevents the major clinical manifestations of cretinism in the fetus.
View details for Web of Science ID A1983QR79600020
View details for PubMedID 6851937
TREATMENT OF OVINE CRETINISM INUTERO WITH 3,5-DIMETHYL-3'-ISOPROPYL-L-THYRONINE
1982; 111 (1): 132-135
Placental transfer of iodothyronines is minimal in most species. The nonhalogenated thyroid hormone analog 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) was administered to pregnant ewes to determine if this compound could prevent cretinism in the thyroidectomized fetal lamb. Pharmacokinetic studies comparing [125I]T3 and [3H]DIMIT resulted in fetal-maternal ratios for [3H]DIMIT which were 5- to 10-fold higher than the ratios for [125I]T3, suggestive of preferential transport of DIMIT across the placenta. Subsequently, DIMIT was administered to three pregnant ewes after hysterotomy and fetal thyroidectomy at 95-98 days gestation. Intramuscular DIMIT (1200-2000 micrograms/day) caused suppression of maternal T4 concentrations from a mean of 4.9 micrograms/dl before hysterotomy to less than 1 micrograms/dl within 1-2 weeks. All three thyroidectomized lambs had clinical signs of cretinism at birth and died. Skeletal and lung maturation were delayed in these animals, all of whom had undetectable serum T4 concentrations. In contrast to DIMIT's proven thyromimetic activity in other fetal animal models, this thyroid hormone analog failed to prevent cretinism in thyroidectomized fetal lambs even when administered to the ewe at a dose that suppressed maternal thyroid function.
View details for Web of Science ID A1982NU99900019
View details for PubMedID 7084108