Lumbar Spine Bone Mineral Apparent Density Research Articles

Association Between Vitamin D Insufficiency and Impaired Bone Density Among Adolescents With Perinatally Acquired HIV Infection.

Stunting and pubertal delay are common among children growing up with human immunodeficiency virus (HIV) and are associated with bone and muscle impairments. We investigated factors associated with bone density and muscle function in adolescents living with HIV (ALWH). The VITALITY trial (PACTR202009897660297) investigated whether vitamin D and calcium supplementation improves musculoskeletal health among ALWH. A total of 842 ALWH aged 11-19 years, established on antiretroviral therapy (ART) for ≥6 months, were enrolled from HIV clinics in Zambia and Zimbabwe. Clinical history and examination were undertaken, and serum 25-hydroxyvitamin D3 (25[OH]D3) was measured. Dual-energy X-ray absorptiometry measured total-body-less-head bone mineral density adjusted for height (TBLH-BMDHT), and lumbar spine bone mineral apparent density (LS-BMAD) z scores. The association between a priori-defined covariates and musculoskeletal outcomes were investigated using baseline enrollment data and multivariable logistic regression. TBLH-BMDHT z scores were impaired (mean, -1.42 for male and -0.63 female participants), as were LS-BMAD z scores (mean -1.15 for male and -0.47 for female participants). In bivariate analysis, early pubertal stage, less physical activity, and older age at ART initiation were associated with lower TBLH-BMDHT z scores. Younger age, early pubertal stage, and low socioeconomic status were associated with lower LS-BMAD z scores. Grip-strength-for-height and jump-power-for-height z scores were associated with lower TBLH-BMDHT and LS-BMAD z scores. Low dietary vitamin D and calcium were associated with lower adjusted TBLH-BMDHT z scores. Lower 25(OH)D3 was associated with lower adjusted TBLH-BMDHT and LS-BMAD z scores. Deficits in bone density are common in ALWH. Vitamin D and calcium supplementation and promotion of exercise may improve musculoskeletal health among perinatally infected ALWH.

Rapid trabecular bone growth in puberty associated with stiffer arteries in adulthood - longitudinal study on healthy young males.

Our aim was to assess the relationships between arterial parameters in adulthood and bone parameters in several locations longitudinally from puberty to 18-years and cross-sectionally at 18-years. 102 healthy male data from a 7-year follow-up study was used to analyse total body (TB), femoral neck (FN) and lumbar spine (LS) mineral content and density by DXA, carotid intima-media thickness (cIMT) by ultrasound, carotid-femoral pulse wave velocity (cfPWV) and heart rate adjusted augmentation index (AIxHR75) by applanation tonometry. Linear regression analysis revealed negative associations between LS bone mineral density (BMD) and cfPWV [ß=-1.861, CI -3.589, -0.132, p=0.035] which remained significant [ß=-2.679, CI -4.837, -0.522, p=0.016] after adjustment to smoking, lean mass, weight category, pubertal stage, physical fitness, and activity. For AIxHR75 similar results were present [ß=-0.286, CI -0.553, -0.020, p=0.035], but were dependent on confounders. Analysis on pubertal bone growth speed showed independent positive associations to AIxHR75 between Δ FN bone mineral apparent density (BMAD) [ß=672.50, CI 348.07, 996.93, p<0.001] and Δ LS BMAD [ß=700.40, CI 57.384, 1343.423, p=0.033]. Further analysis combining pubertal bone growth and adulthood BMC revealed that the relationships of AIxHR75 with LS BMC and ΔFN BMAD were independent of each other. Trabecular bone regions like lumbar spine and femoral neck, showed stronger relationships with arterial stiffness. Rapid bone growth in puberty is related to arterial stiffening, while final bone mineral content relates to decreased arterial stiffness. These results could indicate that bone metabolism is independently associated with arterial stiffness rather than bone and arteries just having common traits of growth and maturation.

Abstract 144: Height adjusted lumbar spine BMD in Turner syndrome: A case control study

Background: Short stature may confound results of areal BMD (aBMD) in Turner's Sydrome (TS). Use of Bone Mineral Apparent Density (BMAD) and Height-for –age Z-score (HAZ) adjusted aBMD are recommended for children with short stature. Conflicting results are obtained regarding BMAD of lumbar spine in TS from previous studies.Aims and Objectives: To assess BMAD and HAZ-adjusted lumbar spine aBMD Z scores in Indian girls with TS.Methodology: BMD using GE LUNAR DXA machine was performed in 33 TS (age 13-21 yrs) & 11 age matched healthy females (Operator CV-1.2%) BMAD and HAZ-adjusted BMD Z scores were calculated from previously published methods from BMDCS study.Results: Although unadjusted BMD at lumbar spine suggested a significant reduction in TS (p=0.0148) compared to controls, there was no significant difference in BMAD (p=0.2051) or HAZ-adjusted aBMD (p=0.4826).Conclusion: Lumbar spine BMAD and HAZ-adjusted aBMDs are not significantly lower in Paediatric Indian TS population. Further studies involving more patients are necessary.

Effect of Ionic Calcium and Vitamin D3 in Lumbar Spine Bone Mineral Density of Paediatric Epileptic Patients on Antiepileptic Drugs

Introduction: Epilepsy is one of the most common neurologic conditions occurring in persons under 21 years of age. Vitamin D deficiency is highly prevalent among children with epilepsy. Antiepileptic drugs (AEDs) are associated with decreased Bone Mineral Density (BMD) as AEDs increase catabolism of 25-hydroxy vitamin D by induction of the hepatic P 450 enzyme system, which leads to relative hypocalcaemia, increased levels of parathyroid hormone (PTH) and subsequently low BMD. Aim: To evaluate the association of ionic calcium and vitamin D3 in paediatric epileptic patients who were on AEDs with BMD. Materials and Methods: This was an observational cross-sectional study carried out at Department of Paediatrics, SPMC, Bikaner, Rajasthan, India from December 2020 to November 2021. A total of 150 epileptic patients aged 5 to 15 years who were on AED therapy for more than six months and a comparable group of 130 age and gender matched healthy individuals participated in this study. Serum vitamin D3, Alkaline Phosphatase (ALP), ionic calcium and phosphorous levels were assessed and compared between both the groups. Using OSTEOPRO DEXA BMD at the lumbar spine was calculated. Mann-Whitney test and t-test were used to compare quantitative data whereas Chi-square test was used to compare qualitative data in two groups. Non parametric tests (Spearman Correlation) were used to explore the correlation between the two variables. The p-value of &lt;0.05 was considered to be statistically significant. Results: The mean age of study group and control group were 9.94±2.61 years and 10.09±2.53 years respectively. Mean serum ionic calcium (1.09±0.13 mmol/L) was significantly lower in study group as compared to controls (1.15±0.13 mmol/L) with p-value &lt;0.001. Mean serum phosphorous and serum ALP levels were not significantly different in study and control group. The mean Vitamin D3 level (16.70±5.35 ng/mL) was lower in children receiving AEDs as compared to controls (19.08±5.39 ng/mL) with p-value &lt;0.001. Serum levels of ionic calcium and Vitamin D3 were found to be significantly lower in groups with polytherapy and enzyme inducer group of AEDs (p&lt;0.05) whereas only statistically significant difference in vitamin D3 was found in subjects with more than two years of AED therapy. The mean Lumbar Spine Bone Mineral Apparent Density (LSBMAD) of the study and control group were 0.47±0.14 g/cm² and 0.61±0.12 g/cm² respectively. Conclusion: Epileptic children receiving multiple drugs for longer duration showed more decline in calcium and serum 25 hydroxy vitamin D compared to those with single drug for shorter duration.

Leptin to adiponectin ratio in puberty is associated with bone mineral density in 18-year-old males

IntroductionInconsistent associations of leptin and adiponectin with bone mineral characteristics in puberty and adolescence have been reported. We aimed to examine the associations between leptin to adiponectin ratio (LAR) in puberty and bone mineral characteristics at the age of 18 years in healthy males. Materials and methods88 white Caucasian boys were investigated at T1 (mean age 12.1 years), T2 (14.0 years) and T3 (18.0 years). Serum leptin and adiponectin were measured and LAR was calculated at T1, T2 and T3, bone mineral density (BMD) and bone mineral apparent density (BMAD) for total body and lumbar spine (LS) at T1 and T3. Spearman correlation coefficient and partial correlation analyses were used to describe the associations between mean pubertal LAR and BMD at T3. ResultsMean pubertal LAR was negatively correlated with both LS BMD (r = −0.23; P < 0.05) and LS BMAD at T3 (r = −0.33; P < 0.05). These associations remained significant also in partial correlation analysis after controlling for total body fat percentage, total testosterone, HOMA-IR and physical activity at T1 (r = −0.31; P < 0.05 and r = −0.41; P < 0.05 respectively). ConclusionLAR in puberty is negatively associated with lumbar spine BMD and lumbar spine BMAD at the age of 18 years.

Effect of HIV infection on growth and bone density in peripubertal children in the era of antiretroviral therapy: a cross-sectional study in Zimbabwe

SummaryBackgroundFaltered linear growth and pubertal delay, which are both common in children with HIV in sub-Saharan Africa, might affect adolescent bone accrual and future fragility fracture risk. We investigated the association of HIV with bone density adjusted for skeletal size in peripubertal children in Zimbabwe.MethodsWe did a cross-sectional study of baseline data from the IMVASK cohort, which enrolled children aged 8–16 years with HIV who had been taking antiretroviral therapy (ART) for at least 2 years, and children of the same age without HIV. Children with HIV were recruited from public sector HIV clinics at Parirenyatwa General Hospital and Harare Central Hospital (Harare, Zimbabwe), and children without HIV were recruited from six schools in the same suburbs that the hospitals serve. Sociodemographic, clinical, and anthropometric data were collected. Dual-energy X-ray absorptiometry (DXA) was used to measure the bone outcomes of total-body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM), and lumbar spine bone mineral apparent density (LS-BMAD), and we assessed the prevalence of low TBLH-BMCLBM and low LS-BMAD (defined by Z-scores of less than −2·0). Size adjustment techniques were used to overcome the size dependence of DXA measurement. We used linear regression models, with multiple imputation for missing data, to assess relationships between risk factors and TBLH-BMCLBM and LS-BMAD Z-scores in children with and without HIV.FindingsWe recruited 303 children with HIV (mean age 12·4 years [SD 2·5]; 151 [50%] girls) and 306 children without HIV (mean age 12·5 years [SD 2·5]; 155 [51%] girls). In children with HIV, median age of HIV diagnosis was 3·0 years (IQR 1·2–5·8), and median ART duration was 8·1 years (6·2–9·5); for 102 (34%) children, ART included tenofovir disoproxil fumarate (TDF). Children with HIV had a higher prevalence of low TBLH-BMCLBM Z-score than children without HIV (29 [10%] of 279 children with available data vs 18 [6%] of 292 with available data; p=0·066) and a higher prevalence of low LS-BMAD Z-score (40 [14%] of 279 vs 17 [6%] of 293 with available data; p=0·0007). HIV and male sex were associated with earlier pubertal (Tanner) stage. The negative associations between HIV and Z-scores for TBLH-BMCLBM and LS-BMAD were more pronounced with pubertal maturation, particularly in girls. Among children with HIV, TDF exposure and orphanhood were associated with lower TBLH-BMCLBM Z-score in confounder-adjusted analysis. Current TDF use (vs non-TDF-based ART) was associated with a reduction in TBLH-BMCLBM Z-score of 0·41 (95% CI 0·08–0·74; p=0·015) and in LS-BMAD Z-score of 0·31 (0·08–0·69; p=0·12).InterpretationDespite ART, HIV is associated with substantial skeletal deficits towards the end of puberty. The extent of bone deficits associated with TDF and its widespread use in children in sub-Saharan Africa are a concern for future adult fracture risk.FundingWellcome Trust.

Effect of HIV Infection on Growth and Bone Density in Peripubertal Children in the Era of Antiretroviral Therapy: A Cross-Sectional Study in Zimbabwe

Background: Poor linear growth and pubertal delay, both common in children with HIV (CWH) in sub-Saharan Africa, may affect adolescent bone accrual and future fragility fracture risk. We investigated the association of HIV with size-adjusted bone density in peri-pubertal children in Zimbabwe. Methods: CWH aged 8-16 years taking ART for ≥2 years from public-sector HIV clinics in Harare, and HIV-uninfected children from schools in the same catchment area, were recruited into a cross-sectional study. Sociodemographic, clinical and anthropometric data were collected. Outcomes were dual-energy X-ray absorptiometry (DXA) measured total-body less-head bone mineral content-for-lean mass adjusted for height (TBLH-BMCLBM) and lumbar spine bone mineral apparent density (LS-BMAD). Linear regression models using multiple imputation for missing data, assessed relationships between risk factors and DXA measures by HIV status, and interaction by sex and pubertal (Tanner) stage. Findings: We recruited 303 CWH and 306 without HIV, mean (SD) age 12.5 (2.5) years and 50% female. Mean ART duration was 7.9 (2.6) years; for 34% ART included tenofovir disproxil fumarate (TDF). The prevalence of low TBLH-BMCLBM and LS-BMAD (Z-Score<-2) was higher in children with than without HIV (10.4% vs. 6.2%, p=0.066; 14.3% vs. 5.8%, p=0.001 respectively). HIV and male sex were associated with earlier Tanner stage. The negative effects of HIV on TBLH-BMCLBM and LS-BMAD were more pronounced with pubertal maturation, particularly in females. Among CWH, years of TDF exposure and orphanhood were strongly associated with lower TBLH-BMCLBM Z-Score in both unadjusted and adjusted analyses. Current TDF use was associated with 0.40 (95%CI 0.07, 0.73; p=0.018) and 0.31 (0.07, 0.69; p=0.110) lower TBLH-BMCLBM and LS-BMAD Z-Scores respectively. Interpretation: Despite ART, HIV is associated with substantial skeletal deficits by the end of puberty. The size of bone deficits associated with TDF and its widespread use in children in sub-Saharan Africa raise concern for future adult fracture risk. Funding Statement: Wellcome Trust. Declaration of Interests: RR (206764/Z/17/Z) RAF (206316/Z/17/Z) are funded by the Wellcome Trust. CK is funded by a National Institute of Health (NIH) Fogarty Trent Fellowship. AMR is partially supported by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement which is also part of the EDCTP2 programme supported by the European Union Grant Ref: MR/R010161/1. All other authors declare no competing interests. Ethics Approval Statement: Ethical and governance approvals were granted by the London School of Hygiene and Tropical Medicine Ethics Committee (Ref: 15333), the Institutional Review Board of the Biomedical Research and Training Institute in Harare (Ref: AP145/2018), the Joint Research Ethics Committee for University of Zimbabwe College of Health Sciences and the Parirenyatwa Group of Hospitals (Ref: 11/18), Harare Central Hospital Ethics Committee (Ref: 170118/04), the Medical Research Council of Zimbabwe (Ref: MRCZ/A/2297) and the Ministry of Primary and Secondary Education Zimbabwe (Ref: C/426/Harare). Guardians provided written informed consent and children provided written assent.

DXA and pQCT derived parameters in Indian children with beta thalassemia major - A case controlled study.

Children with beta thalassemia major (BTM) are known to have reduced bone mass which increases incidence of non-traumatic fractures. Few studies have assessed prevalence of fractures and bone health in underprivileged children with BTM. Our objectives were to 1) determine prevalence of fractures in underprivileged Indian children with BTM, 2) assess size corrected bone density and bone geometry using Dual x-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT) in these children and healthy controls 3) determine predictors of fractures in children with BTM 4) compare differences in bone density between children with BMT with and without fractures. Bone mineral content and areal bone mineral density (aBMD) of lumbar spine and whole body and vertebral fracture assessment (VFA) was performed by DXA in 334 children (3-18years, 167 BTM+167 controls). Volumetric BMD (vBMD) and bone geometry were assessed by pQCT (subset, 70 BTM, 70 healthy) at distal radius. Children with BTM had higher prevalence of vertebral and long bone fractures (p<0.05). DXA aBMD was lower in children with BTM (p<0.05), whereas, lumbar spine bone mineral apparent density (LSBMAD) was higher (p>0.05). Children with BTM had lower total distal radial vBMD, cortical vBMD and strength strain index (SSI) at 66% site whereas, distal radial trabecular vBMD at 4% was higher (p<0.05). On height adjustment, children with BTM had lower muscle area and cortical thickness and higher marrow area (p<0.05) at 66% site. Age, body size, total body less head (TBLH) aBMD and strength strain index (SSI) were important predictors of fractures in children with BTM. Thus, children with BTM had higher prevalence of non-traumatic fractures. Despite lower areal and volumetric densities, they had higher LSBMAD and trabecular densities which may be attributed to erythroid hyperplasia and iron deposition due to inadequate transfusion and chelation. As LSBMAD is raised in these children, it is unlikely to identify BTM subjects at risk of fracture; VFA thus maybe useful in identifying asymptomatic vertebral fractures.

Quantitative computed tomography discriminates between postmenopausal women with low spine bone mineral density with vertebral fractures and those with low spine bone mineral density only: the SHATTER study.

We evaluated the ability of lumbar spine bone mineral apparent density (BMAD), trabecular bone score (TBS) and volumetric bone mineral density (vBMD) to discriminate between postmenopausal women with low areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) with and without vertebral fractures. The discriminatory ability of lumbar spine aBMD was compared with that of BMAD, TBS and vBMD. We studied three groups of postmenopausal women, i.e. group 1, aBMD T-score < - 1.0 and ≥ 1 vertebral fracture (n = 39); group 2, aBMD T-score < - 1.0 and no vertebral fracture, age- and aBMD-matched to group 1 (n = 34); group 3, aBMD score > - 1 and no vertebral fracture, age-matched to group 1 (n = 37). Lumbar spine aBMD was measured by DXA. BMAD was calculated using the DXA scan results. TBS was derived following DXA scan image reanalysis. Lumbar spine vBMD was assessed by quantitative computed tomography and Mindways Pro software. Differences in variables between groups 1, 2 and 3 were examined using general linear univariate modelling approaches. Area under the receiver operating characteristic (ROC) curve was calculated for BMAD, TBS and vBMD to determine the ability of lumbar spine measurement variables to discriminate between group 1 and group 2. A comparison of ROCs was performed. Lumbar spine BMAD and TBS measurement variables were similar for groups 1 and 2. However, vBMD was significantly lower in group 1 and could discriminate between those women with low aBMD with (group 1) and without vertebral fractures (group 2). We conclude that lumbar spine vBMD may discriminate well between postmenopausal women with low aBMD with and without vertebral fractures as it provides a 3D measure of bone mineral density, excludes the posterior elements of the vertebrae and takes into account bone size. A unique feature of the SHATTER study is that groups 1 and 2 were matched for aBMD, thus our study findings are independent of aBMD. Furthermore, we observed that neither BMAD nor TBS could distinguish between women with low aBMD with and without vertebral fractures. The knowledge gained from the SHATTER study will influence clinical and therapeutic decision-making, thereby optimising the care of patients with and without vertebral and other fragility fractures.

Muscle and bone parameters in underprivileged Indian children and adolescents with T1DM.

The incidence of Type 1 diabetes mellitus (T1DM) is increasing and sarcopenia and osteoporosis have been reported to be associated with long standing diabetes. There is scarcity of data on bone health status of children with T1DM. Our aim was to assess bone health parameters [by Dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT)] and muscle strength (by hand grip) in underprivileged Indian children with T1DM. A cross sectional, observational study was conducted in underprivileged children with diabetes attending the out patient clinic for T1DM at a tertiary care hospital. Children with T1DM with disease duration more than 1 year were included in the study. Age and gender matched controls were also enrolled. Data on age, gender, disease duration, anthropometric parameters and HbA1c were collected. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (Lunar iDXA) and peripheral quantitative computed tomography (pQCT, Stratec XCT 2000) and muscle strength by handgrip. Data were analysed using SPSS 25.0. 251 children with T1DM and 250 age gender matched controls were studied. Mean age of T1DM children was 10.8 ± 4.3yrs (controls 10.3 ± 3.6). Mean HbA1C was 9.7 ± 2.1%. The total body less head areal BMD (TBLH aBMD) and lumbar spine bone mineral apparent density (LSBMAD) Z-scores were significantly lower in children with T1DM (-1.5 ± 1.3, -1.3 ± 1.6 respectively) as compared to controls (-0.5 ± 1.3, -0.64 ± 1.5 respectively) (p < 0.05 for both). Z-scores for trabecular and total density (vBMD) were significantly lower in patients with T1DM (-0.7 ± 1.0, -0.7 ± 1.0 respectively) than controls (-0.15 ± 1.2, -0.31 ± 1.1), (p < 0.05) and trabecular density was lower at distal radius with increasing disease duration. Hand-grip strength Z-score was lower in children with T1DM (-3.0 ± 0.5) as compared to controls (-2.8 ± 0.5). Trabecular density and HbA1C concentrations were negatively correlated (R = -0.18, p < 0.05) as was muscle area and HbA1C concentrations (R = -0.17, p < 0.05,). Bone and muscle health were affected in children with poorly controlled T1DM. With increasing disease duration, attention is required for optimising musculoskeletal health.

Association of Serum Testosterone at 12 Years with a Subsequent Increase in Bone Mineral Apparent Density at 18 Years: A Longitudinal Study of Boys in Puberty

Background: Cross-sectional studies have associated serum testosterone with bone mineral density (BMD). However, there is a shortage of prospective longitudinal studies in this domain, leaving it unclear whether changes in testosterone level precede changes in BMD. Objectives: To examine the association between serum testosterone concentration at the age of 12 years and a subsequent increase in BMD by the age of 18 years. Methods: Eighty-eight boys with a mean age of 12.1 ± 0.7 (time point 1 [T1]) and 18.0 ± 0.7 (T2) were investigated. For both time points, serum testosterone was measured from venous blood samples. Total body (TB) and lumbar spine (LS) BMD and bone mineral apparent density (BMAD) were measured. As different brands of DEXA machines were used at T1 and T2, we calculated SD scores (SDS) from samples at T1 and T2 and their change (Δ). As covariates, bone age at T1 and physical activity (PA) by accelerometer at T1 and T2 were measured. Results: Serum testosterone at T1 was positively correlated with TB BMD at T2 (r = 0.28; p < 0.01), Δ TB BMAD SDS (r = 0.47; p < 0.0001) and Δ LS BMAD SDS (r = 0.23; p < 0.05). When additionally controlling for bone age and total PA at T1, the correlation between testosterone at T1 and Δ TB BMAD SDS remained significant (r = 0.32; p < 0.05). Conclusions: Serum testosterone concentration at the age of 12 years is associated with a subsequent increase in TB BMAD by the age of 18 years. This supports the inference that testosterone levels in early puberty may influence subsequent bone mineral accrual.

Bone Health, Body Composition, and Vitamin D Status of Black Preadolescent Children in South Africa.

Optimal bone health is important in children to reduce the risk of osteoporosis later in life. Both body composition and vitamin D play an important role in bone health. This study aimed to describe bone health, body composition, and vitamin D status, and the relationship between these among a group of conveniently sampled black preadolescent South African children (n = 84) using a cross-sectional study. Body composition, bone mineral density (BMD), and bone mineral content (BMC) were assessed using dual x-ray absorptiometry. Levels of 25-hydroxyvitamin D (25(OH)D) (n = 59) were assessed using dried blood spots. A quarter (25%) of children presented with low bone mass density for their chronological age (BMD Z-score < −2) and 7% with low BMC-for-age (BMC Z-score < −2), while only 34% of the children had sufficient vitamin D status (25(OH)D ≥ 30 ng/mL). Lean mass was the greatest body compositional determinant for variances observed in bone health measures. Body composition and bone health parameters were not significantly different across vitamin D status groups (p > 0.05), except for lumbar spine bone mineral apparent density (LS-BMAD) (p < 0.01). No association was found between bone parameters at all sites and levels of 25(OH)D (p > 0.05). Further research, using larger representative samples of South African children including all race groups is needed before any conclusions and subsequent recommendation among this population group can be made.

Influence of Estrogen Receptor Alpha Polymorphism on Bone Mineral Density in Iranian Children

Background: Bone mass acquisition in childhood is directly linked to adult bone mineral density (BMD) and fracture risk. BMD is a heritable trait, more than 70% of its variability among a population is affected by genetic factors. Objectives: In the present study, we wanted to investigate the association between estrogen receptor alpha (ESR1) polymorphisms, PvuII (rs2234693) and XbaI (rs9340799), and bone area, bone mineral content (BMC), and BMD of the lumbar spine, femoral neck, and also of the total body less the head in Iranian children. Methods: The ESR1 gene PvuII and XbaI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Bone area, BMC, BMD, and bone mineral apparent density (BMAD) were assessed by dual-energy X-ray absorptiometry (DEXA). Linear regression was carried out to examine the effects of the ESR1 (PvuII and XbaI) polymorphisms on DEXA outputs when adjusted for confounding factors (i.e., age, sex, BMI, and pubertal stage) in 3 models. Results: ESR1 (PvuII) gene polymorphisms (CT vs. CC) showed significant effects on the BMC of the total body less the head in all 3 models. For ESR1 (XbaI), individuals with the AG genotype had higher lumbar spine BMD and lumbar spine BMAD compared to other genotypes. Conclusions: It seems that the PvuII and XbaI polymorphisms of ESR1 could be associated with BMC and BMD variation in Iranian children and adolescents.

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.

Longitudinal changes in bone parameters in young girls with anorexia nervosa.

Anorexia nervosa (AN) during childhood and adolescence has been reported to adversely affect bone health, but few studies have investigated longitudinal changes. DXA-derived bone parameters and body composition were retrospectively assessed in 111 young girls with AN with a median age of 15.4 years (10.9, 19.8). In 68 (61%) vertebral fracture assessment (VFA) was performed and in 31 (28%), a follow-up DXA was performed. Correlations with growth, changes in body composition and effects of illness duration and menstruation were examined. Size adjusted DXA standard deviation scores were calculated for total body (TB) less head bone mineral content (TBLH-BMC) and lumbar spine bone mineral apparent density (LS-BMAD). Mean (range) bone area (BA) for height centile was 27.1 (0-97), and mean lean mass for height centile was 28.8 (0-95) at baseline. Mean (range) LS BMAD was -1.0 (-2.6, 0.8) SDS at first and - 1.2 (-3.0, -0.2) at second DXA (p = 0.023). On follow up, lean mass for height increased from 27th centile (0, 75) to 40th centile (0, 70) (p = 0.006), and fat mass for height increased from 55 g/cm to 67 g/cm (11.3, 124.2) (p < 0.001). Duration of illness was the only negative predictor of LS BMAD (p < 0.0001). Change in height SDS was the only positive predictor of change in TBLH-BMC (r = 0.384, p = 0.037), and change in LS BMAD (r-0.934, p < 0.0001). Of 68 patients who had VFA, 4 (5.9%) had a mild vertebral fracture. Bones are smaller and less dense in childhood/adolescent AN compared to healthy adolescents. Although there are significant gains in lean mass and fat mass, over time, BMAD SDS decreases slightly. Improvement in BMAD SDS is related to improvement in height SDS.

Amalgamated Reference Data for Size-Adjusted Bone Densitometry Measurements in 3598 Children and Young Adults-the ALPHABET Study.

The increasing use of dual-energy X-ray absorptiometry (DXA) in children has led to the need for robust reference data for interpretation of scans in daily clinical practice. Such data need to be representative of the population being studied and be "future-proofed" to software and hardware upgrades. The aim was to combine all available pediatric DXA reference data from seven UK centers to create reference curves adjusted for age, sex, ethnicity, and body size to enable clinical application, using in vivo cross-calibration and making data back and forward compatible. Seven UK sites collected data on GE Lunar or Hologic Scanners between 1996 and 2012. Males and females aged 4 to 20 years were recruited (n = 3598). The split by ethnic group was white 2887; South Asian 385; black Afro-Caribbean 286; and mixed heritage 40. Scans of the total body and lumbar spine (L1 to L4 ) were obtained. The European Spine Phantom was used to cross-calibrate the 7 centers and 11 scanners. Reference curves were produced for L1 to L4 bone mineral apparent density (BMAD) and total body less head (TBLH) and L1 to L4 areal bone mineral density (aBMD) for GE Lunar Prodigy and iDXA (sex- and ethnic-specific) and for Hologic (sex-specific). Regression equations for TBLH BMC were produced using stepwise linear regression. Scans of 100 children were randomly selected to test backward and forward compatibility of software versions, up to version 15.0 for GE Lunar and Apex 4.1 for Hologic. For the first time, sex- and ethnic-specific reference curves for lumbar spine BMAD, aBMD, and TBLH aBMD are provided for both GE Lunar and Hologic scanners. These curves will facilitate interpretation of DXA data in children using methods recommended in ISCD guidelines. The databases have been created to allow future updates and analysis when more definitive evidence for the best method of fracture prediction in children is agreed. © 2016 American Society for Bone and Mineral Research.

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.

Associations between Bone Mineral Characteristics and Serum Levels of Ghrelin and Peptide YY in Overweight Adolescent Boys

Background/Aims: The role of ghrelin and peptide YY (PYY) in bone mineralization is not fully known. The aim of this study was to determine whether acylated and des-acyl ghrelin and PYY in addition to leptin are related to bone mineral density (BMD) in adolescent overweight boys (OWB) and normal-weight boys (NWB). Participants and Methods: Fifty- five OWB (BMI >85th percentile) and 154 NWB (BMI <85th percentile) aged 12-16 years participated in this study. Fasting serum acylated and des-acyl ghrelin, PYY, leptin, testosterone levels, total body (TB) and lumbar spine (LS) bone mineral content (BMC), and BMD were measured. TB BMC for height and TB and LS bone mineral apparent density (BMAD) were calculated. Results: No differences were seen in acylated and des-acyl ghrelin or PYY levels, while the leptin levels were significantly higher in the OWB compared to the NWB. In the OWB, TB BMAD was positively correlated with acylated ghrelin and leptin, and TB BMC for height was positively correlated with PYY. In the OWB, the variability of TB BMD was determined by TB fat-free mass and des-acyl ghrelin, whereas the variability of TB BMAD was determined by leptin. Conclusions: Des-acyl ghrelin and PYY are involved in the bone mineralization process in puberty, and the impact can vary between normal and overweight subjects.

Serum interferon gamma concentration is associated with bone mineral density in overweight boys

Childhood obesity has recently been linked to low-grade inflammation. Overweight children have slightly different processes of bone accumulation than normal weight children. The possible links between inflammation and bone accumulation have not previously been assessed in overweight children. An exploratory study to assess whether common inflammatory markers are associated with the development of obesity and bone accumulation in childhood. Thirteen different inflammatory markers in serum were measured in 38 boys with BMI >85th centile (overweight) and 38 boys with normal BMI (normal weight), aged 10-11 years. Total body (TB) and lumbar spine (LS) bone mineral density (BMD), bone mineral content (BMC) were measured by DXA. TB BMC for height, TB and LS bone mineral apparent density (BMAD) were calculated. Overweight boys had higher mean TB and LS BMD, TB BMC and TB BMC for height, but lower mean TB BMAD (all p < 0.05) than normal weight boys. Serum interferon gamma (IFNγ) concentration was significantly (p < 0.05) correlated with TB BMD (r = 0.36), TB BMC (r = 0.38) and TB BMC for height (r = 0.53) in the broader overweight group (n = 38). In obese boys (BMI > 95 centile, n = 36) IFNγ was correlated with LS BMD (r = 0.38). The positive correlation between serum INFγ concentration and BMD suggests that the inflammatory process, already involved in the early stage of obesity, may also affect bone accumulation. Further studies are needed to clarify the role of INFγ as a possible link between adipose tissue and bone health.