Neuroradiological features of patients with bilateral macronodular adrenocortical disease and meningiomas associated or not with genetic variants of ARMC5- a case series.

INTRODUCTION: Meningiomas are the most common primary brain and central nervous system tumors, accounting for approximately 40% of these tumors. The most important exams for the radiological study of meningiomas are computed tomography (CT) and magnetic resonance imaging (MRI). We aimed to analyze the radiological features of patients with meningioma related to the simultaneous presence of bilateral macronodular adrenocortical disease (BMAD), with or without pathogenic variants of ARMC5. METHODS: This study included 10 patients who were diagnosed with BMAD. All of them had a radiological diagnosis of expansive brain lesions suggestive of meningioma. All patients underwent brain MRI and a neuroradiolgist analyzed the following parameters: number, site and size of lesions; presence of calcification, edema and bone involvement. RESULTS AND DISCUSSION: Eight patients presented with germline variants of ARMC5; the other 2, did not. The most significant result was the incidence of multiple meningiomas, which was 50% in BMAD patients, whereas the average incidence described thus far is lower than 10%. Considering location, the 22 tumors in the BMAD patients were 5 convexity tumors (22.7%), and 17 skull base tumors (77.2%), the opposite proportion of patients without BMAD. A total of 40.9% of the tumors had calcification, 9% had cerebral edema and 40.9% had bone invasion due to hyperostosis. The literature describes meningioma calcification in 25% of patients, bone invasion by tumor hyperostosis in 20%, and cerebral edema in approximately 60%. CONCLUSION: Relevant results were found considering the rate of multiple meningiomas and tumor location. This finding reinforces the need for further research into the neurological effects caused by genetic variants of ARMC5 in patients with BMAD.

Factors associated with low bone mineral density in Turner syndrome: a multicenter prospective observational study.

Turner syndrome (TS) is associated with a high risk of fracture due to low bone mineral density (BMD). While hypogonadism is known to play a role in decreasing BMD, other factors have not been studied well. Focusing on diet, exercise, and bone metabolism markers, the present, multicentric, prospective, observational study aimed to identify factors contributing to decreased BMD in TS. In total, 48 patients with TS aged between 5 and 49 years comprising a pre-pubertal group (n = 9), a cyclical menstruation group (n = 6), and a hormone replacement therapy (HRT) group (n = 33) were enrolled. The cyclical menstruation group and the HRT group were referred to collectively as the post-pubertal group. The bone mineral apparent density (BMAD) Z-score was higher in the pre-pubertal group than in the post-pubertal group (-0.3 SD vs. -1.8 SD; p = 0.014). Within the post-pubertal group, the median BMAD Z-score was -0.2 SD in the cyclical menstruation group and -2.3 SD in the HRT group (p = 0.016). Spearman's rank correlation revealed no correlation between the BMAD Z-score and bone metabolism markers. No significant relationship was observed between the BMAD Z-score and either the vitamin D sufficiency rate or the step sufficiency rate. A negative correlation was found between BMAD Z-score and serum sclerostin in the pre-pubertal group and serum FSH in the post-pubertal group. In conclusion, the present study found no relationship between the vertebral BMAD Z-score and diet or exercise habits in TS, indicating that estrogen deficiency is the chief reason for low BMD in TS.

Update on the Role of Glucocorticoid Signaling in Osteoblasts and Bone Marrow Adipocytes During Aging.

PURPOSE OF REVIEW: Bone marrow adipose tissue (BMAT) in the skeleton likely plays a variety of physiological and pathophysiological roles that are not yet fully understood. In elucidating the complex relationship between bone and BMAT, glucocorticoids (GCs) are positioned to play a key role, as they have been implicated in the differentiation of bone marrow mesenchymal stem cells (BMSCs) between osteogenic and adipogenic lineages. The purpose of this review is to illuminate aspects of both endogenous and exogenous GC signaling, including the influence of GC receptors, in mechanisms of bone aging including relationships to BMAT. RECENT FINDINGS: Harmful effects of GCs on bone mass involve several cellular pathways and events that can include BMSC differentiation bias toward adipogenesis and the influence of mature BMAT on bone remodeling through crosstalk. Interestingly, BMAT involvement remains poorly explored in GC-induced osteoporosis and warrants further investigation. This review provides an update on the current understanding of the role of glucocorticoids in the biology of osteoblasts and bone marrow adipocytes (BMAds).

Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass.

Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations. Thus, we wished to assess the impact of the MC4R on bone mass and metabolism. Secondly, we wished to investigate the impact of the GLP-1 RA liraglutide on bone mass in adults with pathogenic MC4R mutations. 17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs). Individuals with a BMI above 28 (14 MC4R mutation carriers and 28 matched control participants) underwent 16 weeks treatment with liraglutide 3.0 mg. The MC4R group had higher BMD [mean difference: 0.065 g/m2 (- 0.008 to 0.138), p = 0.03], but BMAD and BTMS were not different compared to the control group. In response to liraglutide, BMAD increased in the control group, compared to no change in the MC4R group [mean group difference: 0.0007 (0.0001-0.001), p = 0.04]. In conclusion, BMD is increased in MC4R causal obesity compared to common obesity, but when corrected for body size (BMAD), bone mass was not increased, and no evidence of an influence of the MC4R on bone metabolism in adults was found. Liraglutide treatment did not change bone metabolism in MC4R causal obesity, but increased bone mass as measured by BMAD in common obesity.

Cross-sectional and longitudinal evaluation of bone mass and quality in children and young adults with juvenile onset systemic lupus erythematosus (JSLE): role of bone mass determinants analyzed by DXA, PQCT and QUS.

INTRODUCTION: There are few prospective data on bone mass and quality in patients with juvenile onset systemic lupus erythematosus (JSLE). There are also few studies analyzing bone mass and quality determinants by using at the same time dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and quantitative ultrasound (QUS). OBJECTIVE: The objective of this paper is to evaluate cross-sectionally and longitudinally bone mass and quality determinants in adolescents and young adults with JSLE, and to identify the main predictors of reduced bone mineral density (BMD) and bone quality using these techniques. METHODS: Fifty-six patients with JSLE (mean age 18.5 ± 5.7 years) entered the study. In all subjects DXA scan at the lumbar spine, radius pQCT and phalangeal QUS were performed the same day. Of these, 46 patients (mean age 23.1 ± 6.2 years) were revaluated with a second DXA, pQCT and QUS. The data obtained were compared with 72 and 80 age- and sex- matched healthy controls. RESULTS: At the first evaluation, JSLE patients had a reduced spine BMAD SDS (p < 0.001), and significantly lower levels of TrabBMD (p < 0.0001), SSIp (p < 0.05), AD-SoS and QUS z-score (p < 0.005) but not reduced muscle CSA and CBA values. CortBMD and FatCSA were significantly increased (p < 0.0001). These data were confirmed at longitudinal evaluation regarding spine BMAD SDS (p < 0.001), TrabBMD (p < 0.0001), FatCSA (p < 0.005), AD-SoS (p < 0.001), and QUS z-score (p < 0.005) but not muscle CSA (p ≤ 0.05) and CBA (p < 0.0001). SSIp and CortBMD longitudinal evaluation showed that JSLE patients did not present significant differences in comparison to controls. CONCLUSIONS: Patients with JSLE have a low bone mass without catch-up growth over time, causing a reduction of peak bone mass with high risk of osteoporosis in early adulthood. To reduce the risk, close monitoring of BMD, better control of disease activity, physical activity and dietary intake of calcium and vitamin D are advocated to ameliorate the loss of bone mass. In patients with proved osteoporosis therapeutic approaches including bisphosphonates should be considered.

Vitamin D levels in children, adolescents, and young adults with juvenile-onset systemic lupus erythematosus: a cross-sectional study.

BACKGROUND: SS and LC contributed equally to this manuscript. Hypovitaminosis D is common in the general population. Although many studies on 25-hydroxyvitamin D (25(OH)D) are available on systemic lupus erythematosus (SLE), few data are reported in juvenile-onset SLE (JSLE) patients. DESIGN: This study aimed to assess serum 25(OH)D levels in JSLE patients and to identify risk factors for vitamin D deficiency in this population. METHODS: Forty-five Caucasian JSLE patients (36 females, nine males; mean age 18.9±6.3 years) and 109 age- and sex-matched healthy controls entered the study. Dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine, serum calcium and phosphate, bone-specific alkaline phosphatase (BSAP), parathyroid hormone (PTH), and 25(OH)D were assessed. The data were compared with an age- and sex-matched control group including 109 Caucasian healthy subjects. RESULTS: JSLE patients exhibited lower 25(OH)D levels than controls (p<0.005), with the lower values observed in patients with active vs. inactive disease (p<0.05). JSLE patients exhibited reduced total calcium levels (p<0.001) and higher phosphate levels (p<0.001), BSAP (p<0.001) and PTH (p<0.001) than controls. In addition, JSLE patients exhibited lower spine bone mineral apparent density (BMAD) SDS values than controls (p<0.001), with higher values in patients with 25(OH)D sufficiency and insufficiency than in those with 25(OH)D deficiency (p<0.001). CONCLUSIONS: Patients with JSLE have significantly lower 25(OH)D levels than controls. Therefore, vitamin D supplementation may be useful to normalize bone mass and quality in subjects with JSLE.

Comparison of bone mass and quality determinants in adolescents and young adults with juvenile systemic lupus erythematosus (JSLE) and juvenile idiopathic arthritis (JIA).

BACKGROUND: Few prospective data have been published on the comparison of bone density and quality in homogeneous groups of patients with juvenile systemic lupus erythematosus (JSLE) and juvenile idiopathic arthritis (JIA). OBJECTIVE AND HYPOTHESIS: The objective of this study is to perform a longitudinal evaluation of the prevalence and the characteristics of bone mass and quality and to evaluate the differences on the bone parameters, using DXA, pQCT and QUS. POPULATION AND/OR METHODS: Forty-three JSLE patients (35 females, 8 males, median age 18.8, range 14.0-34.1 years) have been studied with DXA, pQCT and QUS scans and compared with 138 JIA patients (112 females, 26 males, median age 18.9, range 13.4-33.2 years), and 79 controls (59 females, 20 males; median age 19.3, range 13.5-36.5 years). Of these, 39 patients (32 females and 7 males, median age 20.3, range 16.6-36.8 years) with JSLE were followed longitudinally and compared with 131 patients (108 females, 23 males median age 20.7, range 15.8-37.1 years) with JIA and 63 controls (48 females, 15 males; median age 21.9, range 15.5-38.3 years). RESULTS: JSLE patients have a higher bone cortical density (CrtBMD) than controls and JIA patients (p < 0.005). However, JSLE and JIA patients have a significantly reduced bone trabecular density (TrbBMD) compared to controls (p < 0.0001), with no differences between JSLE and JIA. In addition, JIA patients show a significantly reduced muscle area (MuscleCSA) compared to JSLE and controls (p < 0.001). Conversely, fat area (FatCSA) is significantly increased both in JIA and JSLE patients when compared to controls (p < 0.001), with no differences between the JSLE and JIA groups. Analogous results are observed in the polar resistance to stress (SSIp). On longitudinal evaluation, contrary to CrtBMD, the difference between BMAD SDS, TrbBMD, MuscleCSA and FatCSA remains unchanged; in JSLE patients, SSIp is stable in comparison to JIA and controls without any difference between the two groups. CONCLUSIONS: The evaluation of bone density and structure parameters in JSLE patients highlights significant differences compared with JIA patients and controls. These data might indicate a different pathogenesis of bone damage in the two entities, and suggest a different diagnostic and therapeutic approach to improve the peak bone mass.

Using bone mineral apparent density for BMD adjustment in chronic diseases: Thalassemia an example.

Background: Low BMD is a common problem in major thalassaemia patient, but the use of DXA in chronic disease children with smaller bones, has some problems. Utilizing bone mineral apparent density (BMAD) helps in preventing this obstacle. Testing the usefulness of this method in resolving the effects of bone size on BMD by comparing the BMD and BMAD of our thalassemics with results of our healthy ones, is our goal. Methods: Sample size was 110 cases with mean age of 9.6 ± 4.3 y/o and contained 73 males. Gauge of BMDs done by dual x-ray absorptiometry. Then BMAD was calculated. We did comparison of BMDs and BMADs results of thalassemic children with results of healthy Iranian pediatrics. Results: Mean of femoral BMD and BMAD, spinal BMD and BMAD was 0.579±0.134 g/cm2, 0.162±0.096 g/cm3, 0.563±0.118 g/cm2 and 0.107±0.015, respectively. When results of 9-18 patients compared with BMDs and BMADs of normal children, BMD of femur and BMD and BMAD of spine of patients found significantly lower (P-values, 0.003, <0.001, <0.001, respectively). BMAD of femur of patients was not significantly different from normals. Conclusion: When bone mineral density of femur modifies by bone mineral apparent density formula, the remarkable difference between BMD of patients and normals; vanishes. Utilizing bone mineral apparent density helps in interpretation of femoral dual X-ray absorptiometry at least in thalassemic patients. As the results of vertebrae, after modification by calculating BMAD, remains significantly different, we cannot bring forward BMAD for mentioned aim in the spine of thalassemics.

Somatic Molecular Heterogeneity in Bilateral Macronodular Adrenocortical Disease (BMAD) Differs Among the Pathological Subgroups.

Bilateral macronodular adrenocortical disease (BMAD) is an uncommon cause of Cushing's syndrome leading to bilateral macronodules. Isolated BMAD has been classified into three molecular groups: patients with ARMC5 alteration, KDM1A alteration, and patients without known genetic cause. The aim of this study was to identify by NGS, in a cohort of 26 patients with BMAD, the somatic alterations acquired in different nodules after macrodissection from patients with germline ARMC5 or KDM1A alterations and to analyze potential somatic alterations in a panel of five other genes involved in adrenal pathology (GNAS, PDE8B, PDE11A, PRKAR1A, and PRKACA). Twenty-three patients (7 ARMC5, 3 KDM1A, and 13 BMAD with unknown genetic cause) were analyzable. Somatic ARMC5 or KDM1A events were exclusively observed in patients with germline ARMC5 and KDM1A alterations, respectively. Six out of 7 ARMC5 patients have a high heterogeneity in identified somatic events, whereas one ARMC5 and all KDM1A patients show a loss of heterozygosity (LOH) in all nodules. Except for passenger alterations of GNAS, no genetic alteration susceptible to causing the disease was detected in the BMAD with unknown genetic cause. Our study reinforces our knowledge of the somatic genetic heterogeneity of ARMC5 and the somatic homogeneity of KDM1A. It reveals the absence of purely somatic events in these two genes and provides a new tool for detecting KDM1A alterations by FISH 1p36/1q25.

Disturbed bone marrow adiposity in patients with Cushing's syndrome and glucocorticoid- and postmenopausal- induced osteoporosis.

Background: Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including hormonal signalling. Glucocorticoids (GC) are corticosteroid hormones that promote adipogenic differentiation and are endogenously increased in patients with Cushing´s syndrome (CS). Here, we investigate bone marrow adiposity changes in response to endogenous or exogenous GC increases. For that, we characterize bone biopsies from patients with CS and post-menopausal women with glucocorticoid-induced osteoporosis (GC-O), compared to age-matched controls, including postmenopausal osteoporotic patients (PM-O). Methods: Transiliac crest bone biopsies from CS patients and healthy controls, and from postmenopausal women with GC-O and matched controls were analysed; an additional cohort included biopsies from women with PM-O. Plastic-embedded biopsies were sectioned for histomorphometric characterization and quantification of adipocytes. The fraction of adipocyte area per tissue (Ad.Ar/T.Ar) and marrow area (Ad.Ar/Ma.Ar), mean adipocyte profile area (Ad.Pf.Ar) and adipocyte profile density (N.Ad.Pf/Ma.Ar) were determined and correlated to steroid levels. Furthermore, the spatial distribution of adipocytes in relation to trabecular bone was characterized and correlations between bone marrow adiposity and bone remodeling parameters investigated. Results: Biopsies from patients with CS and GC-O presented increased Ad.Ar/Ma.Ar, along with adipocyte hypertrophy and hyperplasia. In patients with CS, both Ad.Ar/Ma.Ar and Ad.Pf.Ar significantly correlated with serum cortisol levels. Spatial distribution analyses revealed that, in CS, the increase in Ad.Ar/Ma.Ar near to trabecular bone (<100 µm) was mediated by both adipocyte hypertrophy and hyperplasia, while N.Ad.Pf/Ma.Ar further into the marrow (>100 µm) remained unchanged. In contrast, patients with GC-O only presented increased Ad.Ar/Ma.Ar and mean Ad.Pf.Ar>100 µm from trabecular bone surface, highlighting the differential effect of increased endogenous steroid accumulation. Finally, the Ad.Ar/Ma.Ar and Ad.Ar/T.Ar correlated with the canopy coverage above remodeling events. Conclusion: Increased cortisol production in patients with CS induces increased bone marrow adiposity, primarily mediated by adipocyte hypertrophy. This adiposity is particularly evident near trabecular bone surfaces, where hyperplasia also occurs. The differential pattern of adiposity in patients with CS and GC-O highlights that bone marrow adipocytes and their progenitors may respond differently in these two GC-mediated bone diseases.

Boron-mediated aglycon delivery (BMAD) for the stereoselective synthesis of 1,2-cis glycosides.

1,2-cis Glycosides are frequently found in biologically active natural products, pharmaceutical compounds, and highly functional materials. Therefore, elucidating the role of mechanism of their biological activities will help clarify the structure-activity relationships of these diverse compounds and create new lead compounds for pharmaceuticals by modifying their structures. However, unlike 1,2-trans glycosides, the stereoselective synthesis of 1,2-cis glycosides remains difficult due to the nonavailability of neighboring group participation from the 2-O-acyl functionalities of the glycosyl donors. In this context, we recently developed organoboron-catalyzed 1,2-cis-stereoselecitve glycosylations, called boron-mediated aglycon delivery (BMAD) methods. In this review article, we introduce the BMAD methods and several examples of their application to the synthesis of biologically active glycosides.

Spontaneous reshaping of vertebral fractures in an adolescent with osteogenesis imperfecta.

Background: Vertebral compression fractures (VFs) are a common and severe finding in patients with osteoporosis. In children, VFs have the unique potential to reshape and regain their original configuration. Spontaneous vertebral body reshaping (i.e., medication-unassisted) has been reported in secondary osteoporosis. Here we describe a previously unreported spontaneous vertebral reshaping in an adolescent with osteogenesis imperfecta (OI) with multiple vertebral fractures. Case report: A 17-year-old female was diagnosed with OI type I at 5 years of age caused by a novel frameshift variant in COL1A1 (NM_000088.4: c.540delC; p.Met181TrpfsTer84). Due to parental reservations about medication, she had never received bisphosphonate or any other bone active therapy. A lateral spine X-ray demonstrated transparent bones and no VF. However, previous spine X-rays taken at age of 6 years at an external institution showed VFs in T5-7 (Genant semiquantitative method grade I-II). The two lateral spine x-rays, taken 11 years apart, demonstrate that substantial spontaneous vertebral reshaping occurred without bone active therapy during puberty. Discussion: Vertebral reshaping is explained by the stabilization of bone mineral density (BMD) and the remaining growth capacity the children. We hypothesize that spontaneous reshaping may occur in milder forms of OI, and that puberty may be a key mediator of the phenomenon. In all children with OI and vertebral fractures, we nevertheless recommend bisphosphonate therapy since it improves bone mass, BMD, vertebral shape, physical activity and reduces fracture rates.

The extracellular matrix of human bone marrow adipocytes and glucose concentration differentially alter mineralization quality without impairing osteoblastogenesis.

Bone marrow adipocytes (BMAds) accrue in various states of osteoporosis and interfere with bone remodeling through the secretion of various factors. However, involvement of the extracellular matrix (ECM) produced by BMAds in the impairment of bone marrow mesenchymal stromal cell (BM-MSC) osteoblastogenesis has received little attention. In type 2 diabetes (T2D), skeletal fragility is associated with several changes in bone quality that are incompletely understood, and BMAd quantity increases in relationship to poor glycemic control. Considering their altered phenotype in this pathophysiological context, we aimed to determine the contribution of the ECM of mature BMAds to osteoblastogenesis and mineralization quality in the context of chronic hyperglycemia. Human BM-MSCs were differentiated for 21 days in adipogenic medium containing either a normoglycemic (LG, 5.5 mM) or a high glucose concentration (HG, 25 mM). The ECM laid down by BMAds were devitalized through cell removal to examine their impact on the proliferation and differentiation of BM-MSCs toward osteoblastogenesis in LG and HG conditions. Compared to control plates, both adipocyte ECMs promoted cell adhesion and proliferation. As shown by the unmodified RUNX2 and osteocalcin mRNA levels, BM-MSC commitment in osteoblastogenesis was hampered by neither the hyperglycemic condition nor the adipocyte matrices. However, adipocyte ECMs or HG condition altered the mineralization phase with perturbed expression levels of type 1 collagen, MGP and osteopontin. Despite higher ALP activity, mineralization levels per cell were decreased for osteoblasts grown on adipocyte ECMs compared to controls. Raman spectrometry revealed that culturing on adipocyte matrices specifically prevents type-B carbonate substitution and favors collagen crosslinking, in contrast to exposure to HG concentration alone. Moreover, the mineral to organic ratio was disrupted according to the presence of adipocyte ECM and the glucose concentration used for adipocyte or osteoblast culture. HG concentration and adipocyte ECM lead to different defects in mineralization quality, recapitulating contradictory changes reported in T2D osteoporosis. Our study shows that ECMs from BMAds do not impair osteoblastogenesis but alter both the quantity and quality of mineralization partly in a glucose concentration-dependent manner. This finding sheds light on the involvement of BMAds, which should be considered in the compromised bone quality of T2D and osteoporosis patients more generally.

Does Bone Mineral Apparent Density Facilitate Accurate Identification of Osteoporosis in the Short Postmenopausal Women?

OBJECTIVE: Height is one of the most important aspects affecting the areal bone mineral density (BMD). There are several height adjustments in children but none in widespread use for adults. This is specifically a problem in ethnic groups where mean height is substantially lower. We hypothesized that height adjustment of areal BMD would reduce the misclassification in short individuals. MATERIALS AND METHODS: This is a retrospective study involving 373 postmenopausal women. Their records were reviewed and bone mineral apparent density (BMAD) were calculated. Areal BMD T-scores and BMAD T-scores were then compared. RESULTS: The mean height of the cohort was 154.4 cm. There were 47 women who were defined as short (≤147 cm). In short women, BMAD neither showed improvement nor decrement in T-scores, and BMAD T-scores predicted more number of osteoporosis than BMD T-scores. When divided into height ranges, taller women (>160 cm) showed worsening of BMAD T-scores as compared to BMD T-scores (Chi-square test for trend P < 0.001). Hence, BMAD might actually "correct" for larger bone and not shorter bones. CONCLUSION: BMAD was not found to be a suitable alternative in short postmenopausal women to accurately determine whether the low bone density in them is because of dual-energy X-ray absorptiometry artifact or whether they truly have a low density.

Pediatric dual-energy X-ray absorptiometry in clinical practice: What the clinicians need to know.

The importance of childhood and adolescence for bone development and mineral accrual is increasingly accepted, leading to a need of suitable methods for monitoring bone health even in pediatric setting. Among the several different imaging methods available for clinical measurement of bone mineral density (BMD) in children, dual-energy X-ray absorptiometry (DXA) is the most widely available and commonly used due to its reproducibility, negligible radiation dose and reliable pediatric reference data. Nevertheless, DXA in children has some technical specific features that should be known by those physicians who interpret and report this examination. We provide recommendations for optimal DXA scan reporting in pediatric setting, including indications, skeletal sites to be examined, parameters to be measured, timing of follow-up BMD measurements. Adequate report and analysis of DXA examinations are essential to prevent over- and underdiagnosis of bone mineral impairment in pediatric patients. In conclusion, a complete and exhaustive DXA report in children and adolescents is mandatory for an accurate diagnosis and a precise monitoring of pediatric bone status.

Body composition and reproductive function exert unique influences on indices of bone health in exercising women.

Reproductive function, metabolic hormones, and lean mass have been observed to influence bone metabolism and bone mass. It is unclear, however, if reproductive, metabolic and body composition factors play unique roles in the clinical measures of areal bone mineral density (aBMD) and bone geometry in exercising women. This study compares lumbar spine bone mineral apparent density (BMAD) and estimates of femoral neck cross-sectional moment of inertia (CSMI) and cross-sectional area (CSA) between exercising ovulatory (Ov) and amenorrheic (Amen) women. It also explores the respective roles of reproductive function, metabolic status, and body composition on aBMD, lumbar spine BMAD and femoral neck CSMI and CSA, which are surrogate measures of bone strength. Among exercising women aged 18-30 years, body composition, aBMD, and estimates of femoral neck CSMI and CSA were assessed by dual-energy x-ray absorptiometry. Lumbar spine BMAD was calculated from bone mineral content and area. Estrone-1-glucuronide (E1G) and pregnanediol glucuronide were measured in daily urine samples collected for one cycle or monitoring period. Fasting blood samples were collected for measurement of leptin and total triiodothyronine. Ov (n = 37) and Amen (n = 45) women aged 22.3 ± 0.5 years did not differ in body mass, body mass index, and lean mass; however, Ov women had significantly higher percent body fat than Amen women. Lumbar spine aBMD and BMAD were significantly lower in Amen women compared to Ov women (p < 0.001); however, femoral neck CSA and CSMI were not different between groups. E1G cycle mean and age of menarche were the strongest predictors of lumbar spine aBMD and BMAD, together explaining 25.5% and 22.7% of the variance, respectively. Lean mass was the strongest predictor of total hip and femoral neck aBMD as well as femoral neck CSMI and CSA, explaining 8.5-34.8% of the variance. Upon consideration of several potential osteogenic stimuli, reproductive function appears to play a key role in bone mass at a site composed of primarily trabecular bone. However, lean mass is one of the most influential predictors of bone mass and bone geometry at weight-bearing sites, such as the hip.