Bone Mineral Apparent Density Z-scores Research Articles

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.

Association of trabecular bone score and bone mineral apparent density with the severity of bone fragility in children and adolescents with osteogenesis imperfecta: A cross-sectional study.

Osteogenesis imperfecta (OI) is a hereditary skeletal disease characterized by bone fragility. Areal bone mineral density (BMD), evaluated by dual-energy X-ray absorptiometry (DXA), is used to assess bone brittleness. The height-adjusted BMD Z-score (BMDHAZ) is calculated in children and adolescents with OI to reduce the confounding factor of short stature. However, even with the BMDHAZ, severity evaluation in children and adolescents with OI is challenging because certain abnormalities in bone quality cannot be accurately assessed by BMD analysis. The trabecular bone scores (TBS) and bone mineral apparent density (BMAD), which represent the structural integrity of bone and bone-size-associated BMD, respectively, are associated with fracture risk. Recently, age- and sex-specific reference ranges have been reported, enabling the calculation of Z-scores for children. To evaluate which density measurements show the highest correlation with fracture risk, we analyzed the associations between the Z-scores of TBS, BMAD, and BMDHAZ, fracture rate, and genetic variants. We retrospectively reviewed 42 participants with OI aged 5 to 20 years who underwent DXA. COL1A1/2 pathogenic variants were detected in 41 of the 42 participants. In participants with nonsense and frameshift variants (n = 17) resulting in haploinsufficiency and mild phenotype, the TBS Z-score was negatively correlated with fracture rate (FR) (r = -0.50, p = 0.042). In participants with glycine substitution (n = 9) causing the severe phenotype, the BMAD Z-scores were negatively correlated with FR (r = -0.74, p = 0.022). No correlation between the BMDHAZ and FR was observed in both groups. These findings suggest that the TBS and BMAD are useful in assessing children and adolescents with OI with specific genetic variants.

ODP124 Sickle Cell Bone Disease and Response to Intravenous Bisphosphonates in Children

Abstract Purpose To evaluate bone morbidity and the response to intravenous (IV) bisphosphonate therapy in children with Sickle Cell Disease (SCD). Methods We conducted a retrospective review of patient records from 2003 to 2019 at three Canadian pediatric tertiary care centers. Radiographs, magnetic resonance images, and computed tomography scans were reviewed for the presence of avascular necrosis (AVN), bone infarcts, and myositis. IV bisphosphonates were offered for bone pain management. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). Results Forty-six children (20 girls, 43%) had bone morbidity at a mean age of 11.8 years (SD 3.9) including AVN of the femoral (17/46, 37%) and humeral (8/46, 17%) heads, H-shaped vertebral body deformities due to endplate infarcts (35/46, 76%), and non-vertebral body skeletal infarcts (15/46, 32%). Five children (5/26, 19%) had myositis overlying areas of AVN or bone infarcts visualized on magnetic resonance imaging. Twenty-three children (8/23 girls) received IV bisphosphonate therapy. They all reported significant or complete resolution of bone pain. There were no reports of sickle cell hemolytic crises, pain crises or stroke attributed to IV bisphosphonate therapy. Bone mineral apparent density Z-score increased at the lumbar spine (N=14, mean change +0.6, SD 0.4) and total body less head (N=14, mean change +0.5, SD 0.4) after IV bisphosphonate therapy (mean 1.5 years, SD 0.8). Conclusion Children with SCD have the potential for extensive and early-onset bone morbidity. In this series, IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications. Presentation: No date and time listed

Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial

BackgroundOf the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV.Methods/designWe will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11–19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMCLBMZ-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function.DiscussionThis is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings.Trial registrationPan African Clinical Trials Registry PACTR20200989766029. Registered on 3 September 2020

Changes in trabecular bone score and bone density in female adolescents with anorexia nervosa: a longitudinal study

Impaired bone health is a common complication of anorexia nervosa (AN). We aimed to assess longitudinal changes in bone mineral density (BMD) and trabecular bone score (TBS), a measure of bone quality, in female adolescents with anorexia nervosa (AN). We conducted a retrospective longitudinal study of 41 female adolescents with AN who underwent two dual-energy X-ray absorptiometry (DXA) scans. Clinical data, including age, weight, height, body mass index (BMI), and DXA measurements were retrieved from the medical charts. Lumbar bone mineral apparent density (BMAD) was calculated to correct for size. Changes (Δ) in BMD, BMAD, and TBS were examined for correlations with clinical characteristics. Mean ages at the time of DXA scans were 14.8±1.9 and 16.8±2.0 years. There was a significant improvement in anthropometric parameters and DXA measurements at the second DXA scan. However, these values were still significantly lower than expected in the general population. The Δlumbar BMD Z-score was 0.3±0.7, the Δlumbar BMAD Z-score was 0.2±0.7 and the ΔTBS Z-score was 0.5±0.7. ΔTBS Z-score was positively correlated with Δheight Z-score, Δweight Z-score and ΔBMI Z-scores, and negatively correlated height Z-score, weight Z-score and TBS Z-scores at the first DXA scan (p<0.05). Δheight Z-score, ΔBMI Z-score and the progression from early to late puberty were identified as significant independent predictors of Δlumbar BMAD Z-score (p<0.05). During two years of treatment, both BMD and TBS increased significantly. Improvement in height and in weight status, and progression in puberty are predictors of improvement in BMD and TBS.

Associations of Maternal Serum Perfluoroalkyl Substances Concentrations with Early Adolescent Bone Mineral Content and Density: The Health Outcomes and Measures of the Environment (HOME) Study.

Background:Per- and polyfluoroalkyl substances (PFAS) may impair bone accrual and strength via endocrine disruption and nuclear receptor agonism, but human studies are primarily of adults or cross-sectional.Objectives:We assessed associations of individual PFAS and their mixture during pregnancy with child bone mineral content (BMC) and areal bone mineral density (aBMD) at age 12 y.Methods:Among 206 mother–child pairs enrolled in a prospective cohort (2003–2006), we quantified perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in maternal serum collected during gestation or delivery. When children were age 12 y, we performed dual energy X-ray absorptiometry and calculated BMC, aBMD, and bone mineral apparent density (BMAD) -scores for six skeletal sites. We estimated covariate-adjusted -score differences per doubling of individual PFAS using linear regression and assessed the PFAS mixture using quantile g-computation and Bayesian kernel machine regression. We explored whether associations were modified by child’s sex or mediated by whole-body lean mass.Results:In covariate-adjusted models, we found that higher maternal serum concentrations of PFOA, PFNA, and the PFAS mixture were associated with lower total hip and forearm (one-third distal radius) BMC -scores in children. Differences in forearm BMC -scores were [95% confidence interval (CI): , 0.01] and (95% CI: , ) per doubling of PFOA and PFNA, respectively, and (95% CI: , ) per quartile increase in the PFAS mixture. Child’s sex modified PFOA associations for some skeletal sites; for example, differences in spine BMAD -score per doubling were (95% CI: , ) among males and 0.07 (95% CI: , 0.30) among females (modification ). Except for PFNA among females, these associations were not mediated by whole-body lean mass.Discussion:Maternal PFAS concentrations during pregnancy may be associated with lower bone mineral accrual and strength in early adolescence. https://doi.org/10.1289/EHP9424

Gestational organophosphate ester exposures and bone mineral density in early adolescence: The HOME Study

BACKGROUND AND AIM: Optimizing bone mineral density (BMD) in adolescence is critical for life-long bone health. Organophosphate esters (OPEs) are synthetic flame retardants and plasticizers that may have osteotoxic effects via endocrine disruption or nuclear receptor agonism. Animal studies suggest that gestation may be a critical period of susceptibility for the impact of OPEs on bone health, but human studies are lacking. We assessed the relation of maternal urinary OPE metabolite concentrations during pregnancy with early adolescent BMD in a prospective birth cohort study. METHODS: We used data from 223 mother-child dyads enrolled in the HOME Study from Cincinnati, OH area, 2003-2006. We measured bis-2-chloroethyl phosphate (BCEP), bis-(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-n-butyl phosphate (DnBP), and diphenyl phosphate (DPHP) in maternal urine collected at 16- and 26-weeks gestation, and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry in children at age 12 years and calculated height-, age-, sex-, and population ancestry-specific Z-scores for whole body (excluding head), total hip, femoral neck, distal radius, and ultradistal radius areal BMD (aBMD) and spine bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per 2-fold increase in maternal urinary OPE concentrations and assessed effect measure modification by child sex. RESULTS:In adjusted analyses, BDCIPP concentrations were positively associated with aBMD and BMAD Z-scores at most skeletal sites. Z-score differences were between 0.11 and 0.15 and greatest for total hip (β = 0.15, 95% CI: 0.02, 0.29). Associations of DPHP with femoral neck and total hip aBMD differed by child sex. Associations among males were null while DPHP concentrations were inversely associated with femoral neck (β = -0.15, 95% CI: -0.29, -0.02) and total hip (β = -0.15, 95% CI: -0.29, 0.00) aBMD Z-scores among females. CONCLUSIONS:Maternal OPE exposures during gestation may affect early adolescent BMD in a metabolite-, sex-, and bone site-specific manner. KEYWORDS: Chemical exposures, Children's environmental health, Endocrine disrupting chemicals

Trabecular Bone Score Reference Values for Children and Adolescents According to Age, Sex, and Ancestry.

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n= 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r= 0.47) than for aBMD or BMAD Z-scores (r= 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).

Bone densities and bone geometry in children and adolescents with arthrogryposis.

To describe bone densitometry results using lumbar spine dual-energy X-ray absorptiometry and forearm peripheral quantitative computed tomography (pQCT) in children with arthrogryposis multiplex congenita (AMC). Prospective study. Lumbar spine areal bone mineral density (BMD) was measured in 58 participants (mean age 6.8years, range 1month to 19.7years; 26 males). The diagnostic subgroup was Amyoplasia in 27 participants, distal arthrogryposis (unclassified, n=13; type 2A, n=1; type 2B, n=2; type 8, n=2) in 18 patients, an unclassified form of arthrogryposis in 6 patients, and a syndromic form of arthrogryposis in 7 patients. The mean lumbar spine areal BMD was -0.4 (SD: 1.5) which was significantly below 0 (p<0.05, one-sample t-test). The mean lumbar spine bone mineral apparent density z-score (+0.4 [SD: 1.4]), a measure that is largely independent of bone size, was not significantly different from 0 (P>0.05). A subset of 22 patients aged 6years or older (mean age 10.9years, 11 males) had forearm pQCT analysis. Mean z-scores for trabecular and cortical volumetric BMD at the radius were similar to healthy controls. Radius periosteal bone circumference and bone mineral content were appropriate for height. These densitometric results did not differ between patients with Amyoplasia or individuals with other diagnoses. Low areal BMD in children and adolescents with AMC reflects their smaller bone size rather than a specific bone mass deficit. These data do not suggest that children and adolescents with AMC in general require regular monitoring by bone densitometry unless there are specific clinical concerns.

Lumbar Spine Bone Mineral Apparent Density in Children: Results From the Bone Mineral Density in Childhood Study.

Dual-energy X-ray absorptiometry (DXA) is a cornerstone of pediatric bone health assessment, yet differences in height-for-age confound the interpretation of areal bone mineral density (aBMD) measures. To reduce the confounding of short stature on spine bone density, use of bone mineral apparent density (BMAD) and height-for-age Z-score (HAZ)‒adjusted aBMD (aBMDHAZ) are recommended. However, spine BMAD reference data are sparse, and the degree to which BMAD and aBMDHAZ account for height-related artifacts in bone density remains unclear. We developed age-, sex-, and population ancestry‒specific spine BMAD reference ranges; compared height-adjustment methods in accounting for shorter stature; and assessed the stability of these measures over time. Secondary analysis of data from a previous longitudinal study. Children and adolescents aged 5 to 19 years at baseline (n = 2014; 922 males; 22% black) from the Bone Mineral Density in Childhood Study. Lumbar spine BMAD and aBMDHAZ from DXA. Spine BMAD increased nonlinearly with age and was greater in blacks and females (all P < 0.001). Age-specific spine BMAD z-score reference curves were constructed for black and non‒black males and females. Overall, both BMAD and aBMDHAZz scores reduced the confounding influence of shorter stature, but neither was consistently unbiased across all age ranges. Both BMAD and aBMDHAZz scores tracked strongly over 6 years (r = 0.70 to 0.80; all P < 0.001). This study provided robust spine BMAD reference ranges and demonstrated that BMAD and aBMDHAZ partially reduced the confounding influence of shorter stature on bone density.

Progressive bone impairment with age and pubertal development in neurofibromatosis type I.

The present study aims at evaluating bone mineral density (BMD) in a population of children with neurofibromatosis type I (NF-1), with particular focus on changes occurring during growth and pubertal development. Bone metabolic markers and bone status [by dual-energy X-ray absorptiometry scans (DXA) of the total body and lumbar spine with morphometric analysis] were assessed in 50 children (33 males; mean age ± SD, 11.6 ± 4years). Bone mineral apparent density (BMAD), trabecular bone score (TBS), and bone strain (BS) of the lumbar spine (LS) DXA were also obtained. In our cohort areal BMD (aBMD) Z-score was below the mean in 88% of the patients at LS (70% after correction for bone size) and in 86% considering total body (TB) DXA. However, aBMD Z-score was < - 2 in 12% after correction for bone size at LS and TB, respectively. Lumbar spine aBMD Z-score (r = - 0.54, P < 0.0001), LS BMAD Z-score (r = - 0.53, P < 0.0001), and TB Z-score (r = - 0.39, P = 0.005) showed a negative correlation with growth and pubertal development (P = 0.007, P = 0.02, P= 0.01, respectively), suggesting that patients failed to gain as much as expected for age. Bone density impairment becomes more evident with growth and pubertal development in NF-1 patients, thus identifying childhood as the best time frame to introduce prevention strategies aiming at peak bone mass achievement. TBS and BS, providing bone DXA qualitative information, could be useful during longitudinal follow-up for better characterizing bone impairment in these patients.

Low trabecular bone score in adolescent female inpatients with anorexia nervosa

Trabecular bone score (TBS) is an emerging technology that provides information regarding bone microarchitecture. A recent study showed that in healthy girls normal TBS (≥1.35) was achieved within the first year post-menarche. The aims of our study was to assess TBS in adolescents with anorexia nervosa (AN) and to evaluate correlations with clinical, laboratory and densitometric variables. A cohort study of 208 adolescent females (mean age 15.6±1.8y) hospitalized because of AN between 2003 and 2017 was retrospectively assessed. Demographic and clinical data, including age, weight, height, body mass index (BMI), laboratory parameters and bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DXA) were retrieved from the medical charts. Bone mineral apparent density (BMAD) was calculated for each participant. TBS was assessed by reanalyzing DXA spinal images. Mean TBS was 1.308±0.083, lower than the values previously described in healthy adolescents (p<0.001). Compromised microarchitecture was found in 17 participants (8.2%) and partially compromised in 123 (59.1%). TBS was significantly correlated with age, weight standard deviation score (SDS), BMI SDS, BMD measurements of the lumbar spine and total body, BMAD, BMAD Z-score, luteinizing hormone (LH) and 17b-estradiol (E2) level, and was negatively correlated with cortisol (p=0.017). Participants with regular menstruation or secondary amenorrhea had higher TBS than participants who were pre-menarche or with primary amenorrhea (p<0.001). A stepwise linear regression analysis identified BMD L1-4 Z-score and log E2 as independent predictors of TBS. TBS of adolescent females with AN was found to be lower than TBS of healthy adolescents. Prospective longitudinal studies should be undertaken to investigate whether recovery may result in correction of bone microarchitecture.

Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents

Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density (BMD) can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT). We aimed to investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents. Gender dysphoria was diagnosed based on diagnostic criteria according to the DSM-IV (TR). Thirty four female-to-male persons (transmen) and 22 male-to-female persons (transwomen)were included. Patients were allocated to a young (bone age of <15years in transwomen or <14 in transmen) or old group (bone age of ≥15years in transwomen or ≥14years in transmen). All were treated with GnRHa triptorelin and CSHT was added in incremental doses from the age of 16years. Transmen received testosterone esters (Sustanon, MSD) and transwomen received 17-β estradiol. P1NP, osteocalcin, ICTP and BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. In addition, BMAD and Z-scores were calculated. We found a decrease of P1NP and 1CTP during GnRHa treatment, indicating decreased bone turnover (young transmen 95% CI −74 to −50%, p=0.02, young transwomen 95% CI −73 to −43, p=0.008). The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of FN and LS, whereas BMAD Z-scores of predominantly the LS decreased especially in the young transwomen. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased in all groups except for the old transmen. During CSHT BMAD increased and Z-scores returned towards normal, especially of the LS (young transwomen CI 95% 0.1 to 0.6, p=0.01, old transwomen 95% CI 0.3 to 0.8, p=0.04). To conclude, suppressing puberty by GnRHa leads to a decrease of BTMs in both transwomen and transmen transgender adolescents. The increase of BMAD and BMAD Z-scores predominantly in the LS as a result of treatment with CSHT is accompanied by decreasing BTM concentrations after 24months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DXA-scans remain important in follow-up of bone health of transgender adolescents.

Effect of suppression of puberty and cross-sex hormone therapy on bone turnover markers and BMAD in transgender adolescents

Background: Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT).Objective: To investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents.Methods: Thirty four female-to-males (FtMs) and 22 male-to-females (MtFs) were divided into a young and old pubertal group, based on the bone age of 14 years in the FtMs and 15 years in the MtFs. All patients received GnRHa triptorelin. CSHT was prescribed in incremental doses from the age of 16 years. FtMs received testosterone ester mixture and MtFs were treated with 17-β estradiol. BTMs P1NP, osteocalcin and ICTP and the BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. Furthermore, BMAD and Z-scores were calculated.Results: P1NP and 1CTP decreased during GnRHa treatment, indicating decreased bone turnover. Osteocalcin showed an aberrant pattern. A low BMAD Z-score of both FN and LS was observed in the MtFs at start of GnRHa treatment. The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of both FN and LS, however BMAD Z-scores of predominantly the LS decreased. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased. During CSHT BMAD Z-scores increased and returned towards normal, especially of the LS.Conclusion: Suppressing puberty by GnRHa leads to a decrease of BTMs in transgender adolescents. The increase of BMAD and BMAD Z-scores predominantly in the LS as a result of treatment with CSHT is accompanied by decreasing BTM concentrations after 24 months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DEXA-scans remain important in follow-up of transgender adolescents.

Adverse bone health and abnormal bone turnover among perinatally HIV‐infected Asian adolescents with virological suppression

This study aimed to determine the prevalence of low bone mass and assess its relationship with abnormal bone turnover among HIV-infected Asian adolescents. A multicentre, cross-sectional study was conducted at four paediatric HIV centres in Thailand and Indonesia. Perinatally HIV-infected adolescents aged 10-18 years receiving antiretroviral therapy (ART) with virological suppression (HIV RNA < 400 copies/mL) were enrolled. Study assessments included lumbar spine (L2-L4) dual-energy X-ray absorptiometry and measurement of bone turnover markers. Bone mineral density (BMD) and bone mineral apparent density (BMAD) Z-scores were calculated based on Thai normative age- and sex-matched references. Low bone mass was defined as BMD or BMAD Z-scores ≤ -2. Of 396 participants, 57% were female. The median age was 15.0 [interquartile range (IQR) 13.3-16.9] years, and 73% were in Tanner stage 3-5. At enrolment, the median CD4 T-cell count was 734 (IQR 581-907) cells/μL, and 37% were on protease inhibitor (PI)-based regimens. The overall prevalence of lumbar spine BMD and BMAD Z-scores ≤ -2 were 16.4% and 8.3%, respectively. Z-scores were lower with older age, female sex, body mass index (BMI) <5th percentile, boosted PI exposure and CD4 T-cell percentage < 15% before ART initiation. Increased bone turnover markers were inversely associated with BMD and BMAD Z-scores. Low bone mass was linked to older age, female sex, low BMI, boosted PI exposure, and poor immunological status before ART commencement in our cohort of perinatally HIV-infected Asian adolescents. Dysregulation of bone turnover was associated with bone demineralization. Screening for low bone mass should be implemented to identify individuals who might benefit from interventions to preserve bone health.

Impact of Tenofovir Disoproxil Fumarate on Bone Metabolism and Bone Mass among Perinatally HIV-Infected Asian Adolescents

This study aimed to determine the effect of tenofovir disoproxil fumarate (TDF) on bone metabolism and bone mass in HIV-infected adolescents. This was a sub-study of a cross-sectional multicentre bone health trial that enrolled perinatally HIV-infected Thai and Indonesian adolescents (10-18 years) with viral suppression on antiretroviral therapy. Participants were classified into two groups as TDF users and non-users. Bone metabolism-related markers (25-hydroxyvitamin D [25-OHD], intact parathyroid hormone [iPTH], bone turnover biomarkers), and lumbar spine dual-energy X-ray absorptiometry were assessed. Bone mineral density (BMD)/bone mineral apparent density (BMAD) Z-scores were calculated. Of 394 adolescents, 136 (34.5%) and 258 (65.5%) were TDF users and non-users, respectively. Among TDF users, median age (IQR) was 16.1 (14.7-17.4) years and TDF treatment duration (IQR) was 2.3 (1.4-3.1) years. Among TDF non-users, median age (IQR) was 14.3 (12.6-16.4) years. BMD and BMAD Z-scores comparing TDF users with non-users were -0.8 and -0.6 (P=0.27), and -0.3 and -0.2 (P=0.58), respectively. The association between TDF use and iPTH elevation was intensified in adolescents with suboptimal vitamin D levels (25-OHD <30 ng/ml; P=0.001). TDF administration was positively associated with bone resorption marker (P=0.04) and negatively associated with bone formation marker (P=0.04). With data up to 4 years, neither association between TDF use and bone mass loss (BMD: P=0.09; BMAD: P=0.22), nor variation of bone mass Z-scores by TDF treatment duration (BMD: P=0.34; BMAD: P=0.58) was demonstrated. Recent TDF administration was correlated with PTH elevation and bone turnover dysregulation but not with bone mass reduction in our cohort. A study with extended follow-up to ascertain TDF-associated bone mass deterioration is warranted.

Bone and Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disease, leading to progressive denervation atrophy in the involved skeletal muscles. Bone status has been poorly studied. We assessed bone metabolism, bone mineral density (BMD) and fractures in 30 children (age range 15–171months) affected by SMA types 2 and 3.Eighteen children (60%) had higher than normal levels of CTx (bone resorption marker); 25-OH vitamin D was in the lower range of normal (below 20ng/ml in 9 children and below 12ng/ml in 2). Lumbar spine BMAD (bone mineral apparent density) Z-score was below −1.5 in 50% of children. According to clinical records, four children had sustained four peripheral fractures; on spine X-rays, we observed 9 previously undiagnosed vertebral fractures in 7 children. There was a significant inverse regression between PTH and 25-OH D levels, and a significant regression between BMC and BMAD values and the scores of motor-functional tests.Even if this study could not establish the pathogenesis of bone derangements in SMA, its main findings – reduced bone density, low 25OH vitamin D levels, increased bone resorption markers and asymptomatic vertebral fractures also in very young patients – strongly suggest that even young subjects affected by SMA should be considered at risk of osteopenia and even osteoporosis and fractures.

Bone mineral density in children and young adults with neurofibromatosis type 1

Concern for impaired bone health in children with neurofibromatosis type 1 (NF-1) has led to increased interest in bone densitometry in this population. Our study assessed bone mineral apparent density (BMAD) and whole-body bone mineral content (BMC)/height in pediatric patients with NF-1 with a high plexiform neurofibroma burden. Sixty-nine patients with NF-1 (age range 5.2-24.8; mean 13.7 ± 4.8 years) were studied. Hologic dual-energy X-ray absorptiometry scans (Hologic, Inc., Bedford, MA, USA) were performed on all patients. BMD was normalized to derive a reference volume by correcting for height through the use of the BMAD, as well as the BMC. BMAD of the lumbar spine (LS 2-4), femoral neck (FN), and total body BMC/height were measured and Z-scores were calculated. Impaired bone mineral density was defined as a Z-score ≤-2. Forty-seven percent of patients exhibited impaired bone mineral density at any bone site, with 36% at the LS, 18% at the FN, and 20% total BMC/height. BMAD Z-scores of the LS (-1.60 ± 1.26) were more impaired compared with both the FN (-0.54 ± 1.58; P=0.0003) and the whole-body BMC/height Z-scores (-1.16 ± 0.90; P=0.036). Plexiform neurofibroma burden was negatively correlated with LS BMAD (r(s)=-0.36, P=0.01). In pediatric and young adult patients with NF-1, LS BMAD was more severely affected than the FN BMAD or whole-body BMC/height.

Bone density and metabolism in subjects with microdeletion of chromosome 22q11 (del22q11)

Although hypoparathyroidism with hypocalcaemia is one of the most frequent clinical features of monoallelic microdeletion of chromosome 22q11 (22q11DS), bone mass and metabolism have not yet been assessed in these patients. This study aimed to evaluate bone mass and metabolism in a cohort of patients, both children and adults, with 22q11DS. In twenty-eight patients with 22q11DS (median age 12.5, range 6.1-42.8 years), serum levels of ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin and bone-specific alkaline phosphatase (BSAP), and urinary deoxypyridinoline concentrations were evaluated. In these patients, bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) examination, and volumetric BMD (bone mineral apparent density (BMAD)) was calculated. The data obtained from paediatric and adult patients were compared with two age-, sex- and body size-matched healthy subject control groups. Patients with 22q11DS showed a reduced BMAD Z-score compared with controls (P<0.001). These patients also had significantly lower ionised (P<0.001) and total calcium (P<0.05) levels as well as lower PTH levels (P<0.05), compared with the controls. In particular, children and young patients with 22q11DS had significantly lower serum osteocalcin levels (P<0.001), BSAP levels (P<0.001) and urinary deoxypyridinoline concentrations (P<0.001) than controls. These results were not confirmed in adults. Finally, patients with hypoparathyroidism and/or hypocalcaemia at the time of the study showed significantly lower ionised (P<0.001) and total calcium levels (P<0.001), PTH levels (P<0.05), BSAP levels (P<0.001), osteocalcin levels (P<0.001) and urinary deoxypyridinoline concentrations (P<0.001), compared with patients without hypoparathyroidism and/or hypocalcaemia. Nonetheless, the BMAD Z-score did not show substantial differences between these two groups. Subjects with 22q11DS have a significant reduction in bone mass that appears to be more severe in adults who have already attained peak bone mass than in children who are still growing. Therefore, we suggest a close monitoring of bone mass and metabolism in 22q11DS patients.

Effects of Cushing Disease on Bone Mineral Density in a Pediatric Population

To evaluate bone mineral density (BMD) in children with Cushing disease before and after transphenoidal surgery (TSS). Hologic dual-energy x-ray absorptiometry (DXA) scans of 35 children with Cushing disease were analyzed retrospectively. Sixteen of the 35 patients had follow-up DXA scans performed 13 to 18 months after TSS. BMD and bone mineral apparent density (BMAD) for lumbar spine (LS) L1 to L4 and femoral neck (FN) were calculated. Preoperatively, 38% and 23% of patients had osteopenia of the LS and FN, respectively. Both BMD and BMAD Z-scores of the LS were worse than those for the FN (-1.60 +/- 1.37 versus -1.04 +/- 1.19, P = .003), and (-1.90 +/- 1.49 versus -0.06 +/- 1.90, P < .001); postoperative improvement in BMD and BMAD were more pronounced in LS than in the FN (0.84 +/- 0.88 versus 0.15 +/- 0.62, P<.001; and 0.73 +/- 1.13 versus -0.26 +/- 1.21, P = .015). Pubertal stage, cortisol levels, and length of disease had no effect on BMD. In children with Cushing disease, vertebral BMD was more severely affected than femoral BMD and this effect was independent of degree or duration of hypercortisolism. BMD for the LS improved significantly after TSS; osteopenia in this group may be reversible.