High Bone Mineral Density Osteogenesis Imperfecta in a Family with a Novel Pathogenic Variant in COL1A2.

Osteogenesis imperfecta (OI) is a heterogenous group of heritable bone dysplasias characterized by bone fragility, typically low bone mass, joint laxity, easy bruising, and variable short stature. Classical OI is caused by autosomal dominant pathogenic variants in COL1A1 or COL1A2 that result in either reduced production of normal type 1 collagen or structurally abnormal collagen molecules. Pathogenic variants in these genes generally result in low bone mass. Here, we report a family that had 2 affected individuals who presented with minimal trauma fractures and were found to have elevated bone mineral density (BMD) and a previously unreported variant in COL1A2 c.3356C>T p.(Ala1119Val). We report the change in BMD using dual-energy X-ray and peripheral quantitative computed tomography over a 2.3-year period in the proband. This case report highlights the importance of BMD studies and genetic testing in the diagnostic process for brittle bone disorders.

ABCD: Anthropometry, Body Composition, and Crohn Disease.

BACKGROUND: Young individuals with Crohn disease (CD) are at risk of poor bone mineral density (BMD) and reduced lean tissue mass (LTM). The importance of LTM for maintaining skeletal health, in both incident and established CD, is evidenced. We used dual-energy x-ray absorptiometry assessment to identify areal BMD and LTM in individuals with CD. METHODS: In 57 patients with CD (15F; 12.99-14.16 years) anthropometric, disease activity, bone age assessment, and total body dual-energy x-ray absorptiometry measurements were acquired. A 4-step algorithm was used to assess simultaneous bone and body composition data: areal BMD and height z scores, and LTM for height and bone mineral content (BMC) for LTM z scores were calculated. Low z score cut-off values were defined as ≤1 standard deviations below the population means. RESULTS: The CD cohort showed: low areal BMD z scores (P = 0.00); and low LTM for height (P = 0.00) according to defined cut-off values. BMC appeared to be adapting for the lower amount of LTM. Correcting for bone age eliminated the low areal BMD z scores. As expected, LTM for height and BMC for LTM z scores remained unchanged. CONCLUSIONS: We present a useful clinical algorithm to show significant LTM for height deficits, regardless of chronological or bone age, in this CD cohort. BMC seemed to adapt to the reduced LTM, indicating clinically "normal" areal BMD for age when considered for height. The ongoing deficits in LTM may, however, create chronic long-term consequences for bone health. Improving LTM should be a focus of clinical treatment in individuals with CD.

Cystic fibrosis-related bone disease in children: Examination of peripheral quantitative computed tomography (pQCT) data.

BACKGROUND: The investigation of skeletal health data beyond dual X-ray absorptiometry (DXA) is limited in young individuals with CF. We assessed volumetric bone mineral densities (BMD), and bone and muscle parameters using peripheral quantitative computed tomography (pQCT) in individuals with CF and controls, 7.00-17.99 years. METHODS: Peripheral QCT (XCT 3000, Stratec) measurements were made in 53 individuals with CF and 53 controls. Bone mineral content (BMC), total volumetric BMD (vBMD) and cross sectional area (CSA) of the bone were measured at the 4% and 66% sites of the non-dominant tibia and radius. Additionally, trabecular vBMD and bone strength index (BSIc) were measured at the 4% sites, and cortical vBMD, muscle CSA (mCSA) and strength strain index (SSI) were measured at the 66% sites. RESULTS: Pre-pubertal males with CF had greater trabecular vBMD (p=0.01) and total vBMD (p=0.00) at 4% tibia, and greater total vBMD (p=0.02) at 4% radius. Pre-pubertal females with CF had greater total vBMD at 66% tibia (p=0.02) and radius (p=0.04), and cortical vBMD (p=0.04) at the radius. At puberty, the CF cohort had less BMC at 4% tibia (males, p=0.02; females, p=0.01), and smaller mCSA at 66% tibia (males, p=0.02; females, p=0.01). Pubertal CF females had a smaller bone CSA (p=0.01) at 4% tibia, and lower bone strength (SSI) at the tibia (p=0.00) and radius (p=0.05) sites. CONCLUSIONS: Bone strength parameters were not compromised prior to puberty in this CF cohort. At puberty, the bone phenotype changed for this CF cohort, showing several deficits compared to the controls. However, bone strength was adapting to the mechanical demands of the muscle. Altered bone parameters and their implications for lowered bone strength with increased age may be greatly influenced by: the CF cohort remaining smaller for age and/or a reduced bone strain, secondary to reduced muscle force.

The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

BACKGROUND/AIMS: Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. METHODS: A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate <4 mg/kg/year). RESULTS: There was a significant reduction in mean fracture rate from 1.5 ± 1.1 fractures/year at baseline to 0.7 ± 0.7 fractures/year on active treatment. Z-scores for lumbar spine bone mineral density, bone mineral content, volumetric bone mineral density and bone mineral content for lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. CONCLUSION: Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI.

Cystic fibrosis-related bone disease explored using a four step algorithm.

BACKGROUND: A suboptimal bone accrual in young individuals with cystic fibrosis (CF) may be related to the development of a premature CF-related bone disease. Dual energy X-ray absorptiometry (DXA) is the mainstream measure of bone health; however, the influence of body size and lean tissue mass (LTM) on bone data is poorly interpreted. METHODS: Total body dual-energy X-ray absorptiometry (DXA) measurements of bone mineral content (BMC) and LTM in 53 individuals with CF (7.00-17.99years) were compared to 53 sex-matched controls. BMC, height, and LTM in relation to height and BMC Z-scores were calculated and used in a 4-step algorithm. RESULTS: Pubertal females with CF had less total body BMC for age (p=0.02); pre-pubertal males (p=0.05) and pubertal females with CF (p=0.03) were shorter; and pubertal females with CF showed less total body BMC for LTM (p=0.01). CONCLUSIONS: The algorithm showed the following: (1) prior to puberty lowered total body BMC was primarily due to short stature, (2) LTM was appropriate for body size, and (3) pubertal females with CF had significantly less total body BMC for their LTM. Longer controlled trials are needed to clinically interpret CF-related bone disease using DXA derived data that considers patient size and body composition.

Bioelectrical impedance analysis to estimate body composition, and change in adiposity, in overweight and obese adolescents: comparison with dual-energy x-ray absorptiometry.

BACKGROUND: There is a need for a practical, inexpensive method to assess body composition in obese adolescents. This study aimed to 1) compare body composition parameters estimated by a stand-on, multi-frequency bioelectrical impendence (BIA) device, using a) the manufacturers' equations, and b) published and derived equations with body composition measured by dual-energy x-ray absorptiometry (DXA) and 2) assess percentage body fat (%BF) change after a weight loss intervention. METHODS: Participants were 66 obese adolescents, mean age (SD) 12.9 (2.0) years. Body composition was measured by Tanita BIA MC-180MA (Tanita BIA8) and DXA (GE-Lunar Prodigy). BIA resistance and reactance data at frequencies of 5, 50, 250 and 500 kHz, were used in published equations, and to generate a new prediction equation for fat-free mass (FFM) using a split-sample method. Approximately half (n = 34) of the adolescents had their body composition measured by DXA and BIA on two occasions, three to nine months apart. RESULTS: The correlations between FFM (kg), fat mass (kg) and %BF measured by BIA and DXA were 0.92, 0.93 and 0.78, respectively. The Tanita BIA8 manufacturers equations significantly (P < 0.001) overestimated FFM (4.3 kg [-5.3 to 13.9]) and underestimated %BF (-5.0% [-15 to 5.0]) compared to DXA. The mean differences between BIA derived equations and DXA measured body composition parameters were small (0.4 to 2.1%), not significant, but had large limits of agreements (~ ±15% for FFM). After the intervention mean %BF loss was similar by both methods (~1.5%), but with wide limits of agreement. CONCLUSION: The Tanita BIA8 could be a valuable clinical tool to measure body composition at the group level, but is inaccurate for the individual obese adolescent.

Fracture during intravenous bisphosphonate treatment in a child with osteogenesis imperfecta: an argument for a more frequent, low-dose treatment regimen.

BACKGROUND/AIMS: Intravenous bisphosphonate therapy is the mainstay of medical treatment in osteogenesis imperfecta (OI) and has been shown to increase bone mass, decrease bone pain, improve mobility, and reduce the incidence of fractures. Sclerotic metaphyseal lines parallel to the growth plate are seen on long bone radiographs following cyclical intravenous therapy. These areas create stress risers within the bone that may act as foci for subsequent fractures as exemplified in this clinical case. METHODS: An 8-year-old girl with OI sustained a distal radial fracture following 3 years of treatment with 6-monthly intravenous zoledronate. Her diagnosis, response to treatment, and subsequent fracture at a sclerotic metaphyseal line is described. RESULTS: Peripheral quantitative computer tomography was used to characterise the presence of multiple stress risers at the distal forearm. Trabecular bone mineral density fluctuated from 34 to 126% compared to neighbouring 2-mm regions. CONCLUSION: There remain many unanswered questions about optimal bisphosphonate treatment regimens in children with OI. The formation of stress risers following intravenous bisphosphonate treatment raises the hypothesis that a more frequent and low-dose bisphosphonate regimen would provide more uniform dosing of bone in the growing child and reduce the likelihood of fractures compared to current treatment practices.

Evaluation of bone mineral density and morphology using pQCT in children after spinal cord injury.

OBJECTIVE: To evaluate the effects of spinal cord injury (SCI) on bone density and morphology in children using peripheral quantitative computer tomography (pQCT). DESIGN: Retrospective cohort study of 19 paediatric patients with SCI (9 paraplegics and 10 tetraplegics). RESULTS: There was significant reduction in tibial metaphysial volumetric bone mineral density (vBMD), diaphysial cortical cross-sectional area (CSA), cortical thickness and polar strength-strain index. There was a significant loss of calf muscle CSA. Those who were able to stand had greater trabecular vBMD, tibial cortical thickness and tibial muscle CSA Z-scores. Lower limb fractures did not occur if tibial trabecular vBMD was greater than 100 mg/cm³. Tibial geometry following SCI was more circular compared to controls. CONCLUSIONS: pQCT provides a valuable insight into the regional changes in bone and muscle development in children following SCI. Residual muscle function with the ability to weight bear provides a significant benefit to bone development.

Regional changes in bone mineral density following spinal cord injury in children.

OBJECTIVE: To document the serial changes in bone mineral density (BMD) following paediatric spinal cord injury (SCI). DESIGN: Retrospective case series. SETTING: Paediatric tertiary care hospital. PATIENTS: Eighteen children (nine males) followed in an outpatient spinal cord injury service. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Serial bone mineral density (BMD) measurements using dual energy X-ray absorptiometry (DXA). RESULTS: Mean follow-up was 5.0 +/- 3.6 years (range 0.4-12.4 years). Three children sustained minimal trauma fractures, all femoral. For the cohort, BMD Z-scores were significantly less than zero in the legs (-2.7 +/- 2.0, p < 0.001), femoral neck (-2.1 +/- 1.4, p < 0.001), total body (-0.8 +/- 1.3, p=0.02) and lumbar spine (-0.8 +/- 1.6, p=0.04), but not in the arms (-0.2 +/- 1.0, p=0.5). Lean tissue mass (LTM) Z-scores were reduced in the legs (-1.9 +/- 1.3, p < 0.001). Longitudinal data showed an initial decline in lower extremity BMD, BMC and LTM aged-matched Z-scores in the 12 months following SCI, followed by an age appropriate increase thereafter. CONCLUSIONS: Lower extremity osteopenia and sarcopenia develop rapidly in the first 12 months following the SCI. The reduced bone strength increases the risk of low trauma fracture.

Total body protein in healthy adolescent girls: validation of estimates derived from simpler measures with neutron activation analysis.

BACKGROUND: Little recent and accurate information about body protein content in healthy adolescent girls is available. OBJECTIVE: The objective was to assess the total body nitrogen (TBN) and total body protein (TBPr) contents of fat-free mass (P:FFM) in a group of healthy adolescent girls and to validate previously published TBN prediction equations. DESIGN: TBN was measured with in vivo neutron activation analysis (TBNNAA). Bone mineral density and FFM were measured with dual-energy X-ray absorptiometry (FFMDXA), total body water and FFM were measured with bioimpedance analysis, and FFM was assessed by measuring skinfold thicknesses in 51 girls with a mean (+/- SD) age of 14.7 +/- 0.7 y. The validity of the TBN prediction equations was assessed with Bland-Altman analysis. RESULTS: TBNNAA in our adolescent group was higher (1.49 kg) than values reported in earlier studies of women (1.25 and 1.31 kg), and P:FFM was slightly higher (23%) than that documented in adults (19-21%). Previously published TBN equations showed either systematic bias or wide limits of agreement. CONCLUSION: A predictive equation derived from the present study population based on FFMDXA improves the prediction of TBN for groups of young girls but may not be helpful for individuals in clinical settings.

Reduced body protein in children with spastic quadriplegic cerebral palsy.

BACKGROUND: No studies have directly measured body protein or validated skinfold-thickness anthropometry and dual-energy X-ray absorptiometry (DXA) to assess body protein in children with spastic quadriplegic cerebral palsy (SQCP). OBJECTIVE: We aimed to measure and evaluate body protein and to determine whether skinfold-thickness anthropometry and DXA can predict body protein in children with SQCP. DESIGN: This was a cross-sectional study of 59 children (22 girls, 37 boys) aged 3.9-19.5 y with SQCP. The children underwent measurements of anthropometric indexes, lean tissue mass by DXA (LTM(DXA)), and total body protein by neutron activation analysis (TBP(NAA)). In addition, TBP was estimated from both skinfold-thickness anthropometry (TBP(SKIN)) and DXA (TBP(DXA)). The agreement of TBP(SKIN) and TBP(DXA) was tested against TBP(NAA) by using Bland and Altman plot analysis. RESULTS: Height and weight SD scores (x +/- SD: -3.1 +/- 1.6 and -4.8 +/- 5.3, respectively) were significantly lower than reference data in the children with SQCP (P < 0.001). TBP(NAA) for age and height was low in the children with SQCP (P < 0.001): 56.1 +/- 17.3% and 81.5 +/- 15.7%, respectively, of the values predicted from control data. TBP(SKIN) and TBP(DXA) were both highly correlated with TBP(NAA): r = 0.90, P < 0.001, and r = 0.91, P < 0.001, respectively. Despite these significant correlations, agreement analyses showed wide variation of up to 33.3% of the mean for both methods. CONCLUSIONS: Body protein in children with SQCP is significantly reduced for age and height. Skinfold anthropometry and DXA show wide variation in estimation of body protein compared with NAA in this group of children.

Transient disturbance in physeal morphology is associated with long-term effects of nitrogen-containing bisphosphonates in growing rabbits.

UNLABELLED: Bisphosphonates have clinical benefit in children with severe osteogenesis imperfecta or osteoporosis and potential benefit in children with Perthes disease or undergoing distraction osteogenesis. However, there is concern about the effects of bisphosphonates on the physis and bone length. In 44 growing rabbits, zoledronic acid caused a transient disruption of physeal morphology, retention of cartilaginous matrix in trabeculae and cortical bone of the metaphysis, and a minor decrement in tibial bone length at maturity. INTRODUCTION: Data from growing animal models suggest that bisphosphonates cause retention of longitudinal cartilaginous septa at the chondro-osseous junction, extension of trabeculae to the metaphyseal-diaphyseal junction, and varying dose-dependent effects on longitudinal growth. However, there is a lack of data regarding effects of intermittent use of nitrogen-containing bisphosphonates on the physis and on tibial length in models reaching maturity. MATERIALS AND METHODS: Contralateral tibias of juvenile rabbits were examined after right tibial distraction osteogenesis from two previous studies. Animals were randomized to receive 0.1 mg/kg zoledronic acid (ZA) IV at 8 weeks of age (ZA*1) or 8 and 10 weeks of age (ZA*2) or saline. Body mass was analyzed from 5 to 44 weeks of age; tibial length and proximal physeal-metaphyseal histology and histomorphometry were analyzed at 8-52 weeks of age. RESULTS: Tibial length was 3% less at 14 weeks of age in the ZA*2-treated versus saline group (p<0.05) in both studies, and this difference persisted at maturity in the long-term study group (26 weeks of age, p<0.05). Total body mass gain from 5 to 26 weeks of age was 14% less in ZA*2-treated than saline animals (p<0.05). Rate of weight gain from 8 to 10 weeks of age was 76% less in ZA*2 compared with saline animals (p<0.05). Radiographs showed radiodense lines in the metaphyses of ZA-treated bones, corresponding to the number of doses. Histologically, lines resulting from the first dose of ZA contained longitudinal cartilaginous matrix cores surrounded by bone, whereas those from the second dose contained spherical cores of matrix caused by transient disruption of physeal morphology after the first dose of ZA. Resorption of these lines at later times was radiographically and histologically evident, but remnants of cartilaginous matrix remained in the cortical bone of ZA-treated animals. CONCLUSIONS: ZA treatment within the final 13.5% of the rabbit tibial growth period caused a transient disruption in physeal morphology and resorption associated with retention of cartilaginous matrix and coinciding with a persistent 3% decrement in tibial length. Disruption of physeal morphology and potential loss of bone length should be considered when administering nitrogen-containing bisphosphonates to children before closure of the major physes.

Zoledronic acid prevents osteopenia and increases bone strength in a rabbit model of distraction osteogenesis.

UNLABELLED: Prolonged healing times and stress-shielding osteopenia remain problematic in distraction osteogenesis. In this study of 30 rabbits, zoledronic acid increased regenerate volume, mineralization, and tibial strength and prevented osteopenia over a 6-week period. Translation to the clinical setting, if safe, could improve outcomes in distraction osteogenesis in children. INTRODUCTION: Because the external fixators for limb lengthening and reconstruction are designed to control the positions of bone fragments accurately, they also produce stress-shielding effects on the forming regenerate and surrounding bone. Osteopenia, leading to refracture and limitations on rehabilitation, are common consequences, potentially increasing morbidity and detracting from final clinical outcome. MATERIALS AND METHODS: We examined the effect of zoledronic acid on distraction osteogenesis in 42 immature male NZW rabbits. The model chosen results in reliable regenerate formation and stress-shielding osteopenia. Fourteen animals received either Saline, zoledronic acid 0.1 mg/kg at surgery (ZOL), or another dose 2 weeks postoperatively (Redosed ZOL). Rabbits underwent DXA for bone mineral content and bone mineral density in regenerate and surrounding segments of operated and contralateral tibias. After death at 6 weeks, 30 pairs of tibias underwent quantitative computerized tomography (QCT) and four-point bend testing, and 12 were examined by histomorphometry. The study was powered at 0.8 to show differences of 1.3 SDs for mineral and mechanical parameters. RESULTS: Osteopenia observed in tibias of the Saline group was absent in ZOL and Redosed ZOL tibias, the latter exhibiting higher bone mineral density and bone mineral content over contralateral regions (p < 0.01). Regenerate bone mineral content was higher in ZOL and Redosed ZOL versus Saline groups at 4 and 6 weeks (p < 0.01). Cross-sectional area was 49% and 59% greater at 6 weeks in ZOL and Redosed ZOL regenerates compared with the Saline group (p < 0.01). ZOL and Redosed ZOL tibias were 29% and 89% stronger by four-point bending than the Saline group (p < 0.01). Histomorphometry in the regenerate of ZOL and Redosed ZOL groups revealed higher trabecular bone volume and trabecular number compared with the Saline group (p < 0.001). CONCLUSIONS: Zoledronic acid administration led to significantly greater bone area, mineral content, strength, and trabecular number with reduced stress-shielding osteopenia in this model of distraction osteogenesis. These data suggest that intraoperative and postoperative zoledronic acid administration could improve outcomes in children undergoing limb lengthening.

Mid-femur geometry and biomechanical properties in 15- to 18-yr-old female athletes.

PURPOSE: Right-leg mid-femur geometry and biomechanical indices of bone strength were compared among elite cyclists (CYC), runners (RUN), swimmers (SWIM), triathletes (TRI), and controls (C)-10 subjects per group. METHODS: Bone cross-sectional areas (CSA), volumes (Vol), and cross-sectional moments of inertia (CSMI) were assessed by magnetic resonance imaging (MRI), and cortical volumetric bone density (volBMD) was determined as the quotient of DXA-derived bone mineral content (BMC) and MRI-derived cortical bone volume. Bone strength index (BSI) was calculated as the product of cortical volBMD and CSMI. RESULTS: RUN had higher (P < 0.05) size- (femur length and body mass) adjusted (ANCOVA) cortical CSA than C, SWIM, and CYC; and higher size, age, and years of sport-specific training- (YST) adjusted cortical CSA than SWIM and CYC. TRI had higher (P < 0.05) size-adjusted CSA than SWIM. SWIM and CYC had significantly larger (P < 0.05) size-adjusted medullary cavity CSA than RUN and TRI, and the difference between CYC and RUN persisted after additional adjustment for age and YST. RUN had significantly (P < 0.05) greater size-adjusted CSMI and BSI than C, SWIM, and CYC; and higher size, age, and YST-adjusted CSMI and BSI than SWIM and CYC. Mid-femur areal bone mineral density (BMD) was significantly (P < 0.05) higher for RUN compared with CYC only, but there were no other differences among groups for BMC, bone volumes, or volumetric total or cortical BMD. CONCLUSIONS: Running, a weight-bearing exercise, is associated with more favorable geometric and biomechanical characteristics in relation to bone strength, compared with the weight supported activities of swimming and cycling. Differences may reflect skeletal adaptations to the specific mechanical-loading patterns inherent in these sports.

Bone mineral density in adolescent female athletes: relationship to exercise type and muscle strength.

PURPOSE: This study investigated the influence of different exercise types and differences in anatomical distribution of mechanical loading patterns on bone mineral density (BMD) in elite female cyclists, runners, swimmers, triathletes, and controls (N = 15 per group). Associations between leg strength and BMD were also examined. METHODS: Areal BMD (g x cm(-2)) was assessed by duel-energy x-ray absorptiometry (DXA) (total body (TB), lumbar spine (LS), femoral neck (FN), legs, and arms). Right knee flexion and extension strength was measured using a Cybex Norm isokinetic dynamometer at 60 degrees x s(-1). RESULTS: Runners had significantly higher unadjusted TB, LS, FN, and leg BMD than controls (P < 0.05); higher TB, FN, and leg BMD than swimmers (P < 0.05); and greater leg BMD than cyclists (P < 0.05). Absolute knee extension strength was significantly (P < 0.01) correlated (0.33 < or = r < or = 0.44) with TB, FN, LS, and leg BMD for all groups combined. Weaker but still significant correlations (0.28 < or = r < or = 0.33) existed for normalized (per leg lean tissue mass) knee extension strength and all BMD sites, except FN BMD. There were no significant correlations between absolute or normalized knee flexion strength and any of the BMD variables. Absolute knee extension strength was entered as the second independent predictor for LS and leg BMD in stepwise multiple linear regression analysis (MLRA), accounting for increments of 4% and 12%, respectively, in total explained variation. CONCLUSION: We conclude that running, a weight bearing exercise, is associated with larger site-specific BMD than swimming or cycling, that the generalized anatomical distribution of loads in triathlon appears not to significantly enhance total body BMD status, and that knee extension strength is only a weak correlate and independent predictor of BMD in adolescent females.

Body composition in adolescents with anorexia nervosa.

BACKGROUND: Malnourished patients with anorexia nervosa have altered body composition characterized by depletion of fat and fat-free mass. OBJECTIVES: The objectives of this study were to assess the body composition of adolescents with anorexia nervosa compared with that of control subjects and to investigate the relation between simple anthropometric measures and reference techniques for measuring body composition. DESIGN: Twenty-three adolescent females with anorexia nervosa aged 15.46 +/- 1.34 y (x +/- SD) were studied. Body composition was measured by anthropometry, dual-energy X-ray absorptiometry (DXA) (for body fat), and prompt gamma in vivo neutron activation analysis [for total body nitrogen (TBN)]. Twenty-five female subjects provided the control DXA data. TBN measurements were compared with prediction equations based on sex, height, age, and weight. RESULTS: Anorexia nervosa patients had significantly lower weight (40.2 +/- 4.6 kg), body mass index (in kg/m(2): 15.3 +/- 1.2), percentage of body fat (DXA) (13.8 +/- 5.8%), percentage of TBN predicted for age (73 +/- 10%), trunk fat (2.1 +/- 1.0 kg), leg fat (2.6 +/- 1.1 kg), and trunk-to-leg fat ratio than did control subjects (P < 0.05). In anorexia nervosa patients, significant correlations were found between triceps skinfold thickness and percentage of body fat (r = 0.83), body mass index and percentage of body fat (r = 0.46), and body weight and TBN (r = 0.84, P < 0.05). CONCLUSIONS: Hospitalized adolescent females with anorexia nervosa are depleted of total body fat and protein. We identified 3 simple anthropometric measures (triceps skinfold thickness, BMI, and body weight) that can be used to assess body composition and nutritional status in malnourished adolescents with anorexia nervosa.