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* Abbreviations: aBMD — : areal bone mineral density BMAD — : bone mineral apparent density DXA — : dual energy radiograph absorptiometry GnRHa — : gonadotropin hormone releasing hormone agonists Recognition and support are growing for the estimated 0.7% of American teenagers who identify as transgender or gender fluid.1 Many children’s hospitals now offer multidisciplinary care to patients to assist them in transitioning from their designated sex at birth (natal sex or sex assigned at birth) to their affirmed gender. Therapy can begin in early puberty with suppression of sex steroid hormone production followed by supplementation with sex steroids appropriate for their gender identity. The duration of pubertal suppression with gonadotropin hormone releasing hormone agonists (GnRHa) varies but can be as long as 4 years for younger patients who must wait until age 16 to consent for receipt of gender-affirming sex steroid replacement. Much remains unknown about how these manipulations in sex steroids will impact bone geometry, turnover, mass, and strength, all of which contribute to peak bone mass and strength in early adulthood. Peak bone mass and strength attained by early adulthood reflects the culmination of genetic and modifiable influences on bone density and microstructure.2 Sex steroids have differing effects on bone geometry during puberty, with testosterone fostering apposition of bone on the outer cortical surface and estrogen modifying the internal, endocortical area of bone.3 Research into the skeletal effects of hormone therapy for transgender youth is a high priority. The treatment protocols provide a valuable opportunity to distinguish the relative influence of sex steroids versus genetic preprogramming in determining bone development. Beyond the academic questions to be addressed, the onus is on providers to determine if their patients will sustain any adverse effects with respect to their long-term bone health. The influence of this treatment on the skeleton can be assessed noninvasively with dual energy radiograph absorptiometry (DXA), standard or high-resolution peripheral computed tomography, and/or MRI. These tools … Address correspondence to Laura K. Bachrach MD, Department of Pediatrics, Stanford University, 453 Quarry Road, Stanford, CA 94305-5660. E-mail: lkbach{at}stanford.edu

Hormonal contraception is prescribed commonly to adolescents for myriad indications from pregnancy prevention to treatment for acne, hirsutism or dysmenorrhea. Although use of these hormones generally has no effect or benefits bone health in mature premenopausal women, the same may not be true for adolescents. The teen years are a critical period for acquiring peak bone strength. Sex hormones, growth hormone, and insulin-like growth factors (IGFs) interact to modulate the changes in bone size, geometry, mineral content, and microarchitecture that determine skeletal strength. Combined oral contraceptives (COCs) and intramuscular depo medroxyprogesterone (DMPA) can compromise the expected gains in adolescence by altering estrogen and IGF concentrations. Use of these medications has been associated with slower accrual of bone mineral density (BMD) and increased fracture risk in some studies. Far less is known about the skeletal effects of the newer long acting reversible contraceptives (LARCs). This review takes a critical look at the gaps in current knowledge of the skeletal effects of COCs, DMPA, and LARCs and underscores the need for additional research.

Osteoporosis is an under-recognized complication of chronic illness in childhood. This review will summarize recent literature addressing the risk factors, evaluation, and treatment for early bone fragility. Criteria for the diagnosis of pediatric osteoporosis include the presence of low trauma vertebral fractures alone or the combination of low bone mineral density and several long bone fractures. Monitoring for bone health may include screening for vertebral fractures that are common but often asymptomatic. Pharmacologic agents should be offered to those with fragility fractures especially when spontaneous recovery is unlikely. Controversies persist about the optimal bisphosphonate agent, dose, and duration. Newer osteoporosis drugs have not yet been adequately tested in pediatrics, though clinical trials are underway. The prevalence of osteoporosis is increased in children with chronic illness. To reduce the frequency of fragility fractures requires increased attention to risk factors, early intervention, and additional research to optimize therapy and potentially prevent their occurrence.

Purpose 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). Methods 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. Results 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. Conclusions 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.

Concerns about bone health and potential fragility in children and adolescents have led to a high interest in bone densitometry. Pediatric patients with genetic and acquired chronic diseases, immobility, and inadequate nutrition may fail to achieve expected gains in bone size, mass, and strength, leaving them vulnerable to fracture. In older adults, bone densitometry has been shown to predict fracture risk and reflect response to therapy. The role of densitometry in the management of children at risk of bone fragility is less clear. This clinical report summarizes current knowledge about bone densitometry in the pediatric population, including indications for its use, interpretation of results, and risks and costs. The report emphasizes updated consensus statements generated at the 2013 Pediatric Position Development Conference of the International Society of Clinical Densitometry by an international panel of bone experts. Some of these recommendations are evidence-based, whereas others reflect expert opinion, because data are sparse on many topics. The statements from this and other expert panels provide general guidance to the pediatrician, but decisions about ordering and interpreting bone densitometry still require clinical judgment. The interpretation of bone densitometry results in children differs from that in older adults. The terms “osteopenia” and “osteoporosis” based on bone densitometry findings alone should not be used in younger patients; instead, bone mineral content or density that falls >2 SDs below expected is labeled “low for age.” Pediatric osteoporosis is defined by the Pediatric Position Development Conference by using 1 of the following criteria: ≥1 vertebral fractures occurring in the absence of local disease or high-energy trauma (without or with densitometry measurements) or low bone density for age and a significant fracture history (defined as ≥2 long bone fractures before 10 years of age or ≥3 long bone fractures before 19 years of age). Ongoing research will help define the indications and best methods for assessing bone strength in children and the clinical factors that contribute to fracture risk. The Pediatric Endocrine Society affirms the educational value of this publication.

Summary Background 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. Objectives 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). Methods 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. Results 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. Conclusions 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.

Concern for bone fragility in children and adolescents has led to increased interest in bone densitometry. Pediatric patients with genetic and acquired chronic diseases, immobility, and inadequate nutrition may fail to achieve the expected gains in bone size, mass, and strength, which leaves them vulnerable to fracture. In older adults, bone densitometry has been shown to predict fracture risk and reflect response to therapy. The role of densitometry in the management of children at risk of bone fragility is less certain. This clinical report summarizes the current knowledge about bone densitometry in the pediatric population, including indications for its use, interpretation of results, and its risks and costs. This report emphasizes consensus statements generated at the 2007 Pediatric Position Development Conference of the International Society of Clinical Densitometry by an international panel of bone experts. Some of these recommendations are evidence-based, and others reflect expert opinion, because the available data are inadequate. The statements from this and other expert panels have provided general guidance to the pediatrician, but decisions about ordering and interpreting bone densitometry still require clinical judgment. Ongoing studies will help to better define the indications and best methods for assessing bone strength in children and the clinical factors that contribute to fracture risk.

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 experienced5% 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.

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.

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.

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.

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.

Background 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. Study Design 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. Results 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. Conclusions 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.

KELSEY, J. L., L. K. BACHRACH, E. PROCTER-GRAY, J. NIEVES, G. A. GREENDALE, M. SOWERS, B. W. BROWN JR., K. A. MATHESON, S. L. CRAWFORD, and K. L. COBB. Risk Factors for Stress Fracture among Young Female Cross-Country Runners. Med. Sci. Sports Exerc., Vol. 39, No. 9, pp. 1457–1463, 2007. Purpose: To identify risk factors for stress fracture among young female distance runners. Methods: Participants were 127 competitive female distance runners, aged 18–26, who provided at least some followup 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. Results: Eighteen participants had at least one stress fracture during follow-up. Baseline characteristics associated (P G 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 wholebody 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. Conclusion: 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

On April 14, 2005, a workshop on the skeletal effects of pharmacologic agents in children was held at the National Institutes of Health. Jointly sponsored by the American Society for Bone and Mineral Research (ASBMR) and the National Institute of Child Health and Human Development, the meeting was organized in response to suggestions from the Pediatric Bone Initiative of the ASBMR.1 Previous discussions at the 2003 ASBMR symposium on the state of pediatric bone research1 led to the conclusion that there was a lack of information on the effects of Food and Drug Administration–approved therapeutic agents on bone in children. Advances in pediatric medicine have produced a new population of children who are able to live into adulthood with chronic illnesses and were previously thought to have a poor prognosis for survival beyond their childhood years. Medications and direct effects of illness may compromise normal bone mineralization, leading to skeletal deformities and osteopenia at a relatively young age. Several topics discussed at the 2003 ASBMR symposium were further examined and developed in the recent National Institutes of Health workshop, such as the limitations of currently available pediatric bone density–reference data, the challenges of measuring bone mass and strength in children, clinical-trial design, chronic drug effects on growing bone, and therapeutic agents for pediatric bone disorders. The following is a summary of all the presentations from the National Institutes of Health workshop on pediatric bone. Detailed summaries of selected talks are provided as well. The first session provided basic background on normal bone accrual in children, the regulation of skeletal growth, and the effects of calcium, phosphorus, and vitamin D on growing bone. Dr Jeffrey Baron and his co-workers2,3 reviewed the role of the growth plate in linear skeletal growth and work from his own laboratory … Address correspondence to Gordon L. Klein, MD, MPH, University of Texas Medical Branch, Department of Pediatrics, 301 University Blvd, Galveston, TX 77555-0352. E-mail: gklein{at}utmb.edu

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.

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.

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.

The Canadian Panel of the International Society for Clinical Densitometry has developed standards in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. Previously, this group addressed the performance of densitometry in postmenopausal women. This report addresses the use of densitometry in men, premenopausal women, and children with a focus on dual-energy X-ray absorptiometry.

BACKGROUND 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. METHODS 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]). RESULTS 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. CONCLUSIONS 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.

COBB, K. L., L. K. BACHRACH, G. GREENDALE, R. MARCUS, R. M. NEER, J. NIEVES, M. F. SOWERS, B. W. BROWN, JR., G. GOPALAKRISHNAN, C. LUETTERS, H. K. TANNER, B. WARD, and J. L. KELSEY. Disordered Eating, Menstrual Irregularity, and Bone Mineral Density in Female Runners. Med. Sci. Sports Exerc., Vol. 35, No. 5, pp. 711–719, 2003. Purpose: To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners. Methods: 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. Results: 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. Conclusion: 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. Key Words: FEMALE ATHLETES, LONG DISTANCE, OSTEOPENIA, OSTEOPOROSIS, AMENORRHEA, OLIGOMENORRHEA, EATING ATTITUDES, EATING DISORDER INVENTORY, FEMALE ATHLETE TRIAD

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.

Background An average daily calcium intake of 1300 mg is recommended for North American adolescents aged 9-18 y. However, questions remain about these recommendations. Objective 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. Design 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. Results 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. Conclusions Interventions should focus on ensuring adequate calcium intake in midpuberty and on minimizing sedentariness in prepuberty.

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

Pediatric renal transplantation recipients have numerous risk factors for decreased bone mass, including the underlying renal disease, nutritional deficits, decreased physical activity, inflammation and exposure to steroid therapy. The assessment of bone mineralization in children following renal transplantation is fraught with difficulty. Dual energy x-ray absorptiometry (DXA) is the most commonly employed tool to assess bone mineralization. However, DXA has important limitations in children and in individuals with renal disease. This brief review will examine the expected gains in bone size and bone mass during growth and the mechanisms by which renal failure and steroid therapy interrupt these process. In addition, the limitations of DXA for detecting impaired bone mineralization in children with renal disease are reviewed and alternative approaches explored.

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.

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.

Purpose: 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). Methods: 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. Results: 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. Conclusions: 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.

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.

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, p0. 008). CUS warrants further study as a tool for assessing bone mineral acquisition in children.

Rosenbloom AL, Martinez V, Kranzier JH, Bachrach LK, Rosenfeld RG, Guevara-Aguirre J. Natural history of growth hormone receptor deficiency. Acta Paediatr 1999; Suppl 428: 153–6. Stockholm. ISSN 0803–5326 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. □Body composition, growth, growth hormone receptor deficiency, insulinlike growth factor I deficiency, intellectual development, Laron syndrome, natural history

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, p0.05; -0.3 at hip, p0.10; -0.5 for whole body, p0.0005). 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.

Growth hormone (GH) and insulin-like growth factor I (IGF-I) deficiencies have been associated with osteopenia in both children and adults. To examine the effects of growth hormone resistance on bone mineral and body composition, we studied 11 adults (mean age 30 years) with growth hormone receptor deficiency (GHRD, Laron syndrome) and 11 age- and gender-matched controls from Southern Ecuador. Bone mineral and body composition were determined by dual-energy X-ray absorptiometry. Bone physiology was assessed with biochemical markers of bone turnover and dynamic bone histomorphometry. Bone size and body composition differed markedly between subjects with GHRD and controls. Affected adults were 40 cm shorter than controls, had significantly less lean body mass, and had increased percent body fat. Bone mineral content and density (BMD) at the spine, femoral neck, and whole body were significantly lower in adults with GHRD than in controls. Mean BMD Z scores were -1.5 to -1.6 at all sites in affected women and -2.2 to -2.3 in men with GHRD. Estimated volumetric bone density (BMAD) at the spine and femoral neck, however, was not reduced in GHRD. Spine BMAD was 0.210 +/- 0.025 versus 0.177 +/- 0.021 for affected women versus controls (p0.05) and 0.173 +/- 0.018 versus 0.191 +/- 0.025 for men with GHRD versus normals (p = 0.31). Urinary pyridinoline concentrations were significantly greater in adults with GHRD than in controls, while type I collagen C-telopeptide breakdown products and markers of bone formation did not differ. Differences in histomorphometry were limited to a reduction in trabecular connectivity; bone volume and formation rate were similar to controls. These data confirm the importance of the GH/IGF axis in regulating bone size and body composition. The contribution of these peptides to the acquisition and maintenance of bone mineral is less certain since volumetric bone density was preserved despite low levels of IGF-I and IGFBP-3 associated with GH resistance.

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.

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.

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). Wbole-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.

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.

OBJECTIVE: The objective of this study was to compare sex differences in bone deficits among adolescents with anorexia nervosa (AN) and to identify other correlates of bone health. METHOD: Electronic medical records of all patients 9–20 years of age with a DSM-5 diagnosis of AN who underwent dual-energy x-ray absorptiometry (DXA) scans within three months of initial evaluation by the eating disorders program at Stanford between March 1997 and February 2011 were retrospectively reviewed. Whole body bone mineral content Z-scores and bone mineral density (BMD) Z-scores at multiple sites were recorded using the Bone Mineral Density in Childhood Study (BMDCS) reference data. RESULTS: A total of 25 males and 253 females with AN were included, with median age 15 years (interquartile range [IQR] 14–17) and median duration of illness 9 months (IQR 5–13). Using linear regression analyses, no significant sex differences in bone deficits were found at the lumbar spine, total hip, femoral neck, or whole body when controlling for age, %mBMI, and duration of illness. Lower %mBMI was significantly associated with bone deficits at all sites in adjusted models. DISCUSSION: This is the first study to evaluate sex differences in bone health among adolescents with AN, using novel DSM-5 criteria for AN and robust BMDCS reference data. We find no significant sex differences in bone deficits among adolescents with AN except for a higher proportion of females with femoral neck BMD Z-scores

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 p0.001) 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 p0.01) 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 p0.01). 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.

Concern for bone fragility in children and adolescents has led to increased interest in bone densitometry. Pediatric patients with genetic and acquired chronic diseases, immobility, and inadequate nutrition may fail to achieve the expected gains in bone size, mass, and strength, which leaves them vulnerable to fracture. In older adults, bone densitometry has been shown to predict fracture risk and reflect response to therapy. The role of densitometry in the management of children at risk of bone fragility is less certain. This clinical report summarizes the current knowledge about bone densitometry in the pediatric population, including indications for its use, interpretation of results, and its risks and costs. This report emphasizes consensus statements generated at the 2007 Pediatric Position Development Conference of the International Society of Clinical Densitometry by an international panel of bone experts. Some of these recommendations are evidence-based, and others reflect expert opinion, because the available data are inadequate. The statements from this and other expert panels have provided general guidance to the pediatrician, but decisions about ordering and interpreting bone densitometry still require clinical judgment. Ongoing studies will help to better define the indications and best methods for assessing bone strength in children and the clinical factors that contribute to fracture risk.

Background 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. Objectives 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. Methods 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. Results 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. Limitations Small sample size was a limitation. Conclusions 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.

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 experienced5% BMD loss. Vitamin D deficiency was defined as 25-hydroxyvitamin D (25OHD) level of20 ng/mL, insufficiency as 25OHD level of 20-30 ng/mL, and sufficiency as 25OHD level of30 ng/mL.Evaluation of vitamin D and PTH was carried out in 15 participants who experienced BMD loss ofor = 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 of5% 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.

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.

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 < .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. Low body mass index is an important predictor of this reduction in bone mass.

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.

Purpose: To determine the effect of oral contraceptives (OC) on bone mass and stress fracture incidence in young female distance runners. Methods: One hundred fifty competitive female runners ages 18-26 yr were randomly assigned to OC (30 µg 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. Results: 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. Conclusion: 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.

Objective: To evaluate the relationship between chronic glucocorticoid (GC) exposure and bone mineral density (BMD) in children with rheumatic diseases and inflammatory bowel disease. Study design: 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. Results: 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 R 2 = 0.29). The 25(OH)D levels were