Hip Z-scores Research Articles

8749 Skeletal effects among pre and postmenopausal women with hypoparathyroidism (HypoPT); data from the Canadian National Hypoparathyroidism Registry (CNHR)

Abstract Disclosure: H. AbuAlrob: None. S. Hussein: None. H. Afifi: None. D.S. Ali: None. A. Almoulia: None. D. Bole: None. M. Braga: None. P. Chandra: None. A. Cheng: None. R. Cheung: None. J.E. Young: None. J. Hetal: None. S. Khan: None. T.S. Khan: None. J. Malhem: None. H. Malik: None. S. Mehmood: None. A. Millar: None. E. Morgante: None. F. Naveed: None. H. Niazi: None. T.L. Paul: None. A. Prebtani: None. Z. Punthakee: None. J.A. Shaban: None. R. Shah: None. M. Shrayyef: None. M. Shaikh: None. C. Tagra: None. S.R. Teschke: None. I.T. Tauqir: None. S. Van Uum: None. W. Robert: None. M. Ovize: Employee; Self; Amolyt. A.A. Khan: Research Investigator; Self; Amolyt, Ascend Therapeutics (A Besins Healthcare company), Takeda. Introduction: the CNHR registry was established in 2014 with the objectives of identifying the etiology, presentation, natural history and current treatment of hypoPT[1]. Methods: 101 patients with hypoPT were included in this prospective study. Patients completed baseline assessments including 3 site bone mineral density (BMD), trabecular bone score (TBS), fracture risk assessments, and bone biomarkers. Baseline data is presented. Results: A total of 101 participants were enrolled, 83 (82%) were female, and 18 (18%) were male. There were 35 (42%) premenopausal females and 48 (58%) postmenopausal females (PMF). Only PMF were on antiresorptive therapy. Seven (7/8) were on bisphosphonate therapy (i.e., alendronate), and 3 females were on denosumab. Among premenopausal females the average corrected calcium (Ca) was 2.03 mmol/L (SD=0.26), calcium phosphate product (Ca PO4) was 2.75 (SD=0.62), and the eGFR 94.63 mL/min (SD=18.08). The average bone turnover markers among premenopausal women for the Telopeptide-C (CTX) was 242.4 ng/L (SD=209.4) (CTX within the reference range (WRR) 136-689 ng/L) while the Propeptide 1 Collagen (P1NP) was 37.6 ug/L (SD=39.2) (P1NP WRR 19-83 ug/L). Among PMF, the average corrected Ca was 2.22 mmol/L (SD=0.18), Ca PO4 was 2.14 (SD=0.17), and the eGFR 73.9 mL/min (SD=23.0). The average bone turnover markers among PMF for CTX was 346.1 ng/L (SD=488.4) (WRR 177-1015 ng/L) while P1NP was 47.1 ug/L (SD=33.1) (WRR 16-98 ug/L). Among premenopausal women (n=35), the mean total hip Z-score was 0.87 (SD=1.29), L1-L4 Z-score 0.98 (SD=1.19), FN Z-score 0.59(SD=1.17), and 1/3R Z-score -0.04 (SD=0.77). Among PMF (n=48) the mean total hip T-score was -0.20 (SD=1.65), L1-L4 T-score -0.24 (SD=1.88), FN T-score -0.43(SD=1.59), and 1/3R T-score -0.94(SD=1.23).TBS scores in premenopausal women were normal (TBS=1.41 (SD=0.10)) however the TBS was partially degraded among PMF (TBS= 1.28(SD=0.15)). Fracture data has previously been reported3. Conclusion: The effects of hypoPT on bone strength needs further study2. Our data suggests that bone quality maybe impaired in PMF with hypoPT as noted by the presence of degraded TBS scores and the presence of fragility fracture in this population. Reference 1.Khan AA et al Canadian national hypoparathyroidism registry: an overview of hypoparathyroidism in Canada. Endocrine 2021. 2.Khan AA et al JBMR 2022 Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines from the Second International Workshop3.Hussein S et al. Skeletal effects of hypoparathyroidism (HypoPT); data from the Canadian National Hypoparathyroidism Registry (CNHR). Available here: https://amolytpharma.com/wp-content/uploads/2023/10/ASBMR-CNHR_FINAL.pdf Presentation: 6/2/2024

The association of gender-affirming hormone therapy duration and body mass index on bone mineral density in gender diverse adults

IntroductionFeminizing and masculinizing gender-affirming hormone therapy (fGAHT, mGAHT) results in bone mineral density (BMD) maintenance or improvement over time in transgender and gender diverse (TGD) adults. Mostly European TGD studies have explored GAHT’s impact on BMD, but the association of BMI and BMD in TGD adults deserves further study. ObjectiveTo determine whether GAHT duration or BMI are associated with BMD and Z-scores among TGD young adults. MethodsCross-sectional study of nonsmoking TGD adults aged 18–40 years without prior gonadectomy or gonadotropin-releasing hormone agonist (GnRHa) therapy taking GAHT for > 1 year. BMD and Z-scores were collected from dual-energy x-ray absorptiometry. Associations between femoral neck, total hip, and lumbar spine BMDs and Z-scores and the predictors, GAHT duration and BMI, were estimated using linear regression. ResultsAmong 15 fGAHT and 15 mGAHT, mean BMIs were 27.6 +/- standard deviation (SD) 6.4 kg/m2 and 25.3 +/- 5.9 kg/m2, respectively. Both groups had mean BMDs and Z-scores within expected male and female reference ranges at all three sites. Higher BMI among mGAHT was associated with higher femoral neck and total hip BMDs (femoral neck: β = 0.019 +/- standard error [SE] 0.007 g/cm2, total hip: β = 0.017 +/- 0.006 g/cm2; both p < 0.05) and Z-scores using male and female references. GAHT duration was not associated with BMDs or Z-scores for either group. ConclusionsZ-scores in young, nonsmoking TGD adults taking GAHT for > 1 year, without prior gonadectomy or GnRHa, and with mean BMIs in the overweight range, were reassuringly within the expected ranges for age based on male and female references. Higher BMI, but not longer GAHT duration, was associated with higher femoral neck and total hip BMDs and Z-scores among mGAHT. Larger, prospective studies are needed to understand how body composition changes, normal or low BMIs, and gonadectomy affect bone density in TGD adults.

Cross-sectional study of patients with VCP multisystem proteinopathy 1 using dual-energy x-ray absorptiometry.

VCP multisystem proteinopathy 1 (MSP1), encompassing inclusion body myopathy (IBM), Paget's disease of bone (PDB) and frontotemporal dementia (FTD) (IBMPFD), features progressive muscle weakness, fatty infiltration, and disorganized bone structure in Pagetic bones. The aim of this study is to utilize dual-energy x-ray absorptiometry (DXA) parameters to examine it as a biomarker of muscle and bone disease in MSP1. DXA scans were obtained in 28 patients to assess body composition parameters (bone mineral density [BMD], T-score, total fat, and lean mass) across different groups: total VCP disease (n = 19), including myopathy without Paget's ("myopathy"; n = 12) and myopathy with Paget's ("Paget"; n = 7), and unaffected first-degree relatives serving as controls (n = 6). In the VCP disease group, significant declines in left hip BMD and Z-scores were noted versus the control group (p ≤ .03). The VCP disease group showed decreased whole body lean mass % (p = .04), and increased total body fat % (p = .04) compared to controls. Subgroup comparisons indicated osteopenia in 33.3% and osteoporosis in 8.3% of the myopathy group, with 14.3% exhibiting osteopenia in the Paget group. Moreover, the Paget group displayed higher lumbar L1-L4 T-score values than the myopathy group. In MSP1, DXA revealed reduced bone and lean mass, and increased fat mass. These DXA insights could aid in monitoring disease progression of muscle loss and secondary osteopenia/osteoporosis in MSP1, providing value both clinically and in clinical research.

A skeleton in a huff: insights in etiologies of osteosclerosis.

A 30-yr-old man developed right lower leg pain and a palpable solid mass. Radiographic imaging revealed a periosteal reaction with an exostotic mass arising from the right distal fibula. Generalized skeletal osteosclerosis with periosteal reaction was discovered on a radiographic skeletal survey. A biopsy of the right fibular mass revealed reactive woven bone. The patient was referred to a metabolic bone disease clinic, where laboratory values were consistent with secondary hyperparathyroidism and increased bone turnover. A DXA bone density scan revealed high bone density, with an L1-4 spine Z-score of +9.3, a left femoral neck Z-score of +8.5, and a total hip Z-score of +6.5. A dental exam revealed generalized gingival inflammation, teeth mobility, generalized horizontal alveolar bone loss and widening of the periodontal ligament space, increased bone density around the teeth, and thickening of the radicular lamina dura. An extensive evaluation was performed, with the result of a single test revealing the diagnosis. The differential diagnoses of osteosclerosis affecting the skeleton, teeth, and oral cavity are discussed.

Bone health in transgender assigned female at birth people: effects of gender-affirming hormone therapy and gonadectomy.

Gender-affirming hormone therapy (GAHT) and gender-affirming surgery (GAS) may be desired by transgender and gender-diverse (TGD) individuals who want to affirm their gender identity. Testosterone is the basis of GAHT for transgender individuals assigned female at birth (AFAB), whereas GAS can involve hysterectomy, bilateral salpingectomy, bilateral oophorectomy (BO), thorax masculinization, and phalloplasty. Our study aimed to evaluate the effects of GAHT on the bone health of TGD AFAB individuals who have undergone or not undergone BO. This was a single-center, longitudinal study with retrospectively collected data. TGD AFAB GAHT-naïve individuals were enrolled and underwent dual-energy X-ray absorptiometry scans and laboratory tests (hormonal and bone metabolism parameters) at baseline and after 5 and 10 years of GAHT. Two hundred and forty-three TGD AFAB people were included in this study. Seventy-five subjects had completed data for 5 years and 19 subjects for 10 years of GAHT. At baseline, low bone density (Z-score < -2.0) was found in 2.5% (6/243) of subjects for lumbar spine (LS), whereas total hip (TH) and femoral neck (FN) Z-scores and laboratory tests were within the normal female range. After stratifying by physical activity, the physically active group showed significantly higher LS BMD and Z-scores (p ≤ 0.05). Five years after the start of GAHT, a significant reduction in LS (p ≤ 0.05), TH (p ≤ 0.001), and FN (p ≤ 0.01) Z-scores was detected. A significant reduction in the Z-scores of all three bone sites was observed only in the subgroup that had undergone BO. After 5 years of GAHT, estradiol levels were significantly decreased compared to those in baseline (p ≤ 0.001). Significantly higher estradiol levels were detected in the 5-year no-BO subgroup compared to those in the 5-year BO subgroup (p ≤ 0.001). A significant reduction in LS and TH Z-scores were observed after 10 years of GAHT. At this time, estradiol levels were significantly decreased compared to those in baseline (p ≤ 0.01). Bone density in TGD AFAB individuals is comparable to that in their peers prior to GAHT and BO, but those subjects who underwent BO had a reduced Z-score at LS, FN, and TH after 5 years and at LS after 10 years of GAHT.

Reductions in Bone Mineral Density Are Apparent Early in Children With Prevalent Osteonecrosis Lesions Following Leukemia Therapy.

Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one-time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty-six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z-scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (-1.09 ± 1.53 versus -1.27 ± 1.25, p = 0.549). LS BMD Z-scores declined from baseline to 12 months in children with ON (-0.31 ± 1.02) but not in those without (0.13 ± 0.82, p = 0.035); the hip BMD Z-scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (-1.77 ± 1.22) compared to those without (-1.03 ± 1.07, p = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z-scores were lower in children with ON (hip -0.98 ± 0.95 versus -0.28 ± 1.06, p = 0.010; TB -1.36 ± 1.10 versus -0.48 ± 1.50, p = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.15-2.13; p = 0.004), and hip BMD Z-score at MRI (OR 2.23; 95% CI, 1.02-4.87; p = 0.046) were independently associated with ON. Overall, one-third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z-scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z-scores at MRI were significantly associated with prevalent, off-therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

#3539 CALCIUM ISOTOPE RATIOS IN SERUM ARE THE STRONGEST PREDICTOR OF BONE CALCIUM BALANCE IN PATIENTS ON DIALYSIS

Abstract Background and Aims Dysregulated mineral homeostasis is common in chronic kidney disease (CKD) and associated with bone demineralization and vascular calcification. The balance between bone formation and resorption, which reflect the bone calcium (Ca) balance (BCaB), cannot be determined without bone biopsy which is invasive and not easily repeatable. Recently, we have shown that stable (i.e. non-radioactive) Ca isotopes, 42Ca and 44Ca, can be measured in serum and their ratio (δ44/42Caserum) quantitatively determines net bone gain or loss of Ca. Thus, when bone formation exceeds bone resorption, the net BCaB is positive and δ44/42Caserum is high, and when bone resorption is the predominant process δ44/42Caserum is low compared to age-matched controls. In this study we compared δ44/42Caserum against δ44/42Cabone and arterial biopsy samples (δ44/42Caartery) and the sensitivity of δ44/42Ca in predicting changes in bone histology. Method Adults receiving chronic dialysis who underwent bone and arterial biopsies at the time of kidney transplantation were recruited. Patients who had parathyroidectomy or received cinacalcet or anti-resorptive agents were excluded. All participants had Dual Energy X-ray Absorptiometry (DXA) of the hip and lumbar spine. Ca44 and Ca42 measurements were performed in serum and bone and arterial biopsy samples using a multi-collector inductively-coupled plasma mass spectrometer (Thermo Fisher Scientific, Germany). Results Nineteen patients, median age 59.8 years, 84% male, median time on dialysis 3.3 years were included. δ44/42Ca was significantly higher in serum compared to bone or arterial biopsy samples (p &amp;lt; 0.0001), with the lowest isotope ratios in bone (Fig. 1A). δ44/42Cabone was significantly lighter than δ44/42Caartery (p = 0.0002; Fig. 1B). δ44/42Cabone correlated positively with the osteoblastic markers BAP and P1NP (p = 0.0006, R2 = 0.51 and p = 0.009, R2 = 0.31) and inversely with PTH and the osteoclastic marker RANKL (p = 0.0017, R2 = 52 and p = 0.02, R2 = 0.29 respectively; Fig. 2). Both the DXA hip and lumbar spine T-scores and z-scores correlated positively with δ44/42Cabone. δ44/42Caserum showed an inverse correlation with the osteoid area (p = 0.04, R2 = 0.22) and a positive correlation with the absolute mineralized area and the trabecular thickness (p = 0.0004, R2 = 0.58 and p = 0.013, R2 = 0.34 respectively. The were no significant correlations with δ44/42Caartery. On multivariable linear regression analysis significant predictors of δ44/42Caserum were δ44/42Cabone (p = 0.018, 95%CI −1.35 to −0.16), age (p = 0.02, 95%CI 0.002 to 0.02) and BAP (p = 0.019, 95%CI 0.04 to 0.38), together predicting 71% of the variability in δ44/42Caserum. The only significant predictor of δ44/42Cabone was the δ44/42Caserum: p = 0.004, 95%CI −1.6 to −0.37, model R2 = 69%. Conclusion δ44/42Caserum is a significant and independent maker of BCaB, correlating with bone histology measures, and may provide a more sensitive measure than DXA or bone biomarkers. Further studies are required to determine the clinical utility of using δ44/42Caserum to guide management of mineral bone disease in CKD.

RF06 | PSAT147 Impairments in volumetric bone mineral density, bone microarchitecture, and estimated strength in women with atypical anorexia nervosa

Abstract While anorexia nervosa is associated with impaired skeletal integrity, less is known about the skeletal effects of atypical anorexia nervosa, in which psychological criteria for anorexia nervosa are met, but affected individuals are not low weight. Mean bone mineral density (BMD) is higher in atypical anorexia nervosa than in low-weight anorexia nervosa but lower than in healthy controls. However, it is unknown whether bone microarchitecture and strength are affected. We hypothesized that bone microarchitecture and estimated strength would be impaired in women with atypical anorexia nervosa. This was a cross-sectional study of women ages 21-46 years (n=55): n=28 with atypical anorexia nervosa (body mass index (BMI) &amp;gt;18.5 kg/m2), n=27 healthy, normal weight, eumenorrheic controls. Exclusion criteria included use of oral contraceptives. Areal BMD (aBMD) was assessed by DXA. Volumetric BMD (vBMD), microarchitecture, and failure load (a bone strength estimate) at the distal tibia and radius were assessed by high-resolution peripheral quantitative CT. Median(IQR) BMI was lower [19.4(18.6,20.2) vs 22.2(21.5,23.0), p&amp;lt;0.0001] and median serum 25OH vitamin D level was higher [31(24,39) vs 22(17,25), p=0.0001] in atypical anorexia nervosa than healthy controls. In the atypical anorexia nervosa group, 89% had a history of low weight, 21% had a history of overweight/obesity, 31% had current amenorrhea, and 88% had a history of amenorrhea; median duration of anorexia nervosa was 11(5,14) years. Median lateral spine, total hip, femoral neck, and total radius aBMD Z-scores were lower in atypical anorexia nervosa than healthy controls [lateral spine: -1.1(-2.0,-0.1) vs -0.4(-0.7,0.4), total hip: -0.8(-1.3,0.2) vs 0.2(-0.4,0.7), femoral neck: -0.9(-1.4,0.1) vs -0.1(-0.9,0.6), radius: -0.2(-0.9,0.3) vs 0.1(-0.4,0.6); p≤0.04 for all]. At the tibia, median total, cortical, and trabecular vBMD; cortical thickness; trabecular bone volume fraction; and failure load were lower in atypical anorexia nervosa than healthy controls (p&amp;lt;0.05). At the radius, median trabecular number was lower and trabecular separation was higher in atypical anorexia nervosa than healthy controls (p≤0.04), but there was no difference in failure load between the groups. After controlling for baseline BMI, differences at the radius but not tibia remained significant. At the tibia and radius, median total vBMD, cortical vBMD, and cortical thickness were lower in atypical anorexia nervosa subjects with amenorrhea compared to healthy controls and to atypical anorexia nervosa subjects with eumenorrhea (p≤0.04). Conclusions We demonstrate that, despite normal weight, women with atypical anorexia nervosa have impaired vBMD, microarchitecture, and estimated strength compared to healthy controls, with differences more pronounced at the weight-bearing tibia vs non-weight-bearing radius. Individuals with amenorrhea had additional impairments in the non-weight-bearing radius, suggesting an effect of systemic estrogen deficiency. Our data suggest that current normal weight is not protective against impaired bone structure and strength in atypical anorexia nervosa. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m.

Prevalence and risk factors of fractures in transfusion dependent thalassemia - A Hong Kong Chinese population cohort.

ObjectiveTo delineate the prevalence and associated risk factors of low BMD, osteoporosis/bone fragility and fracture in transfusion‐dependent thalassemia (TDT) in the Chinese population in Hong Kong.Design, Patients and MeasurementsA retrospective cohort study design was employed. Patients of TDT who had serial Hologic dual‐energy X‐ray absorptiometry (DXA) from 2010 to 2016 and received regular transfusion for at least 5 years were recruited. Clinical and biochemical data, from 5 years before the first DXA scan, were retrieved from the electronic record system of the Hospital Authority, till 30 June 2020. Low bone mineral density and osteoporosis/bone fragility are defined by the ISCD 2019 position guidelines.ResultsSeventy‐seven patients were included in the analysis. The fracture prevalence of TDT among the Chinese population in Hong Kong was 15.58%. Up to 55.84% of patients had low bone mineral density, and 5.19% patients had osteoporosis/bone fragility state. The median age at first fracture was 31.73 years (range 24.06–44.18 years). In the regression analysis, a higher log(10) transformation of average ferritin levels over 5 years before the first DXA scan was significantly associated with fracture occurrence regardless of bisphosphonate treatment (OR 310.73, 95% CI 3.99–24183.89, p = .010). Mean average ferritin level over 5 years was 6695.5 ± 2365.7 pmol/L (fracture group) versus 4350.7 ± 3103.2 pmol/L (non‐fracture group), p = .016. Hip and spine BMD Z‐score did not have statistically significant association with fracture occurrence.ConclusionIron overloading plays an important role in adverse bone health in TDT. Dual X‐ray densitometry is insufficient in predicting fracture risk.

Osteogenesis Imperfecta: characterization of fractures during pregnancy and post-partum

BackgroundPregnancy and breastfeeding are associated with bone density loss. Fracture occurrence during pregnancy and post-partum, and its determinants, remain poorly known in Osteogenesis Imperfecta (OI). The aim of this study was to characterize fractures that occurred during pregnancy and post-partum in OI patients.ResultsWe conducted a retrospective multicentric study including a total of 50 previously pregnant OI women from 10 Bone Centers in France. Among these patients, 12 (24%) patients experienced fractures during pregnancy or in the 6 months following delivery, and 38 (76%) did not experience any fracture. The most frequent localizations were: proximal femur (25%), spine (25%), distal femur (12.5%), and pelvis (12.5%). Fractures during pregnancy occurred during the third trimester and post-partum fractures occurred with a mean delay of 2 months following delivery. No fractures occurred during childbirth.We next compared the 12 patients with pregnancy or post-partum fractures with the 38 patients without fractures. Mean age at pregnancy was 32.7 ± 3.1 years-old in the fractured group, vs 29.3 ± 5.0 years-old in the non-fractured group (p = 0.002). Breastfeeding was reported in 85.7% of patients in the fractured group, vs 47.1% in the non-fractured group (p = 0.03). All patients with post-partum fractures were breastfeeding. Bone mineral density was significantly lower in patients with pregnancy-related fractures compared with other patients: spine Z-score − 2.9 ± 1.6DS vs − 1.5 ± 1.7DS (p = 0.03), and total hip Z-score − 2.0 ± 0.7DS vs − 0.5 ± 1.4DS (p = 0.04). At least one osteoporosis-inducing risk factor or disease other than OI was identified in 81.8% vs 58.6% of fractured vs non-fractured patients (not significant). Fracture during pregnancy or post-partum was not associated with the severity of OI. Bisphosphonates before pregnancy were reported in 16.7% and 21.1% of patients with pregnancy-related fractures and non-fractured patients, respectively (not significant).ConclusionsOI management during pregnancy and post-partum should aim for optimal control of modifiable osteoporosis risk factors, particularly in patients with low BMD. Breastfeeding should be avoided.

Serum Vitamin D Level and Bone Mineral Density Among Adolescent Idiopathic Scoliotic Patients

Background: Low bone mineral density (BMD) and low vitamin D were found to be in adolescent idiopathic scoliosis (AIS) patients. The incidence of AIS with osteoporosis is believed to reduce the intensity of the bone by about 20-38 percent Aim: To assess vitamin D level and BMD in patients with adolescent scoliosis. Methods: This work was done in Al-Azhar University hospitals and involved 112 patients diagnosed with AIS and a Cobb angle > 10o aged from 10 - 18 years old. Vitamin D level, Cobb angle and BMD measured in all subjects. Results: Our result included 112 patients, seventy-four (66.1%) of the patients had vitamin D deficiency. Osteopenia present in 39% and osteoporosis in 25% of AIS patients by lumbar spine Z-score and by hip Z-score, osteopenia present in 53% and osteoporosis in 12% of AIS patients. Conclusion: We concluded that majority of AIS patients have low serum vitamin D and low BMD.

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

Increased Bone Mineral Density in Male Patients With Idiopathic Hypogonadotropic Hypogonadism Who Undergo Sex Hormone Therapy: Findings From Cross-Sectional and Longitudinal Studies

ObjectiveThis retrospective observational study assessed the long-term impact of pulsatile gonadotropin-releasing hormone, combined gonadotropin, or testosterone replacement therapy on total hip, femoral, and lumbar bone mineral density (BMD) and Z-scores in adult men with idiopathic hypogonadotropic hypogonadism (IHH). MethodsIn the cross-sectional study, 69 patients were allocated to untreated (n = 42) and treated (n = 27) groups. The untreated group included IHH patients without hormone therapy history, while the treated group included age- and body mass index-matched patients who had received hormone therapy for at least 5 years. The longitudinal study included 53 IHH patients, and their hip and lumbar BMDs were measured several times during hormone therapy. We then evaluated the changes in their BMD. ResultsOur cross-sectional study showed that the treated group had a significantly higher BMD and Z-score for total hip, femoral neck, and lumbar spine (P < 0.001 for all) than the untreated group, and the average bone mass even reached the age-matched normal range. The prevalence of low BMD was 80.95% and 11.11% in untreated and treated groups, respectively. In the longitudinal study (N = 53), the total hip, femoral neck, and lumbar spine BMD gradually increased during treatment. The lumbar spine showed a greater increment in BMD compared with the total hip and femoral neck (P < 0.05). ConclusionSex hormone therapy improved hip and lumbar spine BMD and Z-scores in patients with IHH. The lumbar spine showed a greater improvement in BMD compared with the total hip and femoral neck.

Bone Mineral Density Evolution and Its Determinants in Long-term Survivors of Childhood Acute Leukemia: A Leucémies Enfants Adolescents Study.

This prospective study aimed to analyze determinants that can influence bone mineral density evolution in childhood acute leukemia survivors. Patients included were selected from the long-term follow-up LEA cohort and had dual energy radiograph absorptiometry scan between 10 and 18 years and after the age of 18. All scans were centrally reviewed. Bone mineral density was measured at the lumbar spine, femoral neck, total hip, and whole body, and expressed as z-score. Eighty-nine patients (female 39, lymphoblastic leukemia 68, relapse 25, hematopoietic stem cell transplantation 44, and mean age 15.4 and 20.1 years at the first and second scans, respectively) were studied. The first and second scan z-scores were significantly correlated (P < 10−3). Mean femoral neck and total hip z-scores improved significantly between the first and second scans, whereas no significant evolution occurred at the lumbar spine and whole-body level. On the second evaluation, 14.6% of patients had z-score <−2 at the lumbar spine and 4.3% at the femoral neck level. Gender, type of leukemia, transplantation, relapse, cumulative corticosteroid doses, or growth hormone deficiency did not have any significant impact on z-score variation. Younger age at diagnosis (≤8.5 years) proved an unfavorable risk factor for z-score evolution at the lumbar spine (P = 0.041); the trend did not reach statistical significance for metabolic syndrome (P = 0.054). At the femoral neck, both were associated with unfavorable z-score evolution (P = 0.003 and 0.025, respectively). Patients treated at a younger age and those with metabolic syndrome seem to be at higher risk of bone mineral density decline and should benefit from specific interventions.

Routine serum biomarkers, but not dual-energy X-ray absorptiometry, correlate with cortical bone mineral density in children and young adults with chronic kidney disease.

Biomarkers and dual-energy X-ray absorptiometry (DXA) are thought to be poor predictors of bone mineral density (BMD). The Kidney Disease: Improving Global Outcomes guidelines suggest using DXA if the results will affect patient management, but this has not been studied in children or young adults in whom bone mineral accretion continues to 30 years of age. We studied the clinical utility of DXA and serum biomarkers against tibial cortical BMD (CortBMD) measured by peripheral quantitative computed tomography, expressed as Z-score CortBMD, which predicts fracture risk. This was a cross-sectional multicentre study in 26 patients with CKD4 and 5 and 77 on dialysis. Significant bone pain that hindered activities of daily living was present in 58%, and 10% had at least one low-trauma fracture. CortBMD and cortical mineral content Z-scores were lower in dialysis compared with CKD patients (P = 0.004 and P = 0.02). DXA BMD hip and lumbar spine Z-scores did not correlate with CortBMD or biomarkers. CortBMD was negatively associated with parathyroid hormone (PTH; r = -0.44, P < 0.0001) and alkaline phosphatase (ALP; r = -0.22, P = 0.03) and positively with calcium (Ca; r = 0.33, P = 0.001). At PTH <3 times upper limit of normal, none of the patients had a CortBMD below -2 SD (odds ratio 95% confidence interval 7.331 to infinity). On multivariable linear regression PTH (β = -0.43 , P < 0.0001), ALP (β = -0.36, P < 0.0001) and Ca (β = 0.21, P = 0.005) together predicted 57% of variability in CortBMD. DXA measures did not improve this model. Taken together, routinely used biomarkers, PTH, ALP and Ca, but not DXA, are moderate predictors of cortical BMD. DXA is not clinically useful and should not be routinely performed in children and young adults with CKD 4-5D.

Bone health in young adult survivors born extremely preterm or extremely low birthweight in the post surfactant era.

Most infants born extremely preterm (EP; <28weeks' gestation) or extremely low birthweight (ELBW; <1000g birthweight) in the post surfactant era (early 1990s) are now surviving into adulthood. Preterm birth/low birthweight are risk factors for reduced bone growth and mineralisation in infants and children. However, little is known about their bone health around peak bone mass and through adult life. To compare bone health (bone mineral measures, bone structure and strength) in young adults born EP/ELBW with controls (>2499g birthweight), and within the EP/ELBW group examine perinatal and later variables associated with long term bone health. A geographic cohort comprising all 297 survivors born EP/ELBW in 1991-92 in the state of Victoria, Australia, and 260 contemporaneous controls (>2499g birthweight) were recruited into a longitudinal study from birth. At age 25years, investigations included dual energy X ray absorptiometry and peripheral quantitative computed tomography to measure bone, muscle and soft tissue variables, and fasting blood samples to measure serum 25 hydroxyvitamin D (25(OH)D) and bone turnover markers (BTM). Linear regression analysis, with models fitted using generalised estimating equations, was used to compare outcomes between groups, adjusting for height and weight. Compared with controls (n=129), young adults born EP/ELBW (n=162) had lower areal bone mineral density (g/cm2) (mean difference [MD] -0.044; 95% confidence interval [CI] -0.076,-0.013) and Z-scores (MD -0.53; 95% CI -0.75, -0.30) in the femoral neck, and lower total hip Z-score (MD -0.35; 95% CI -0.54, -0.15) after adjusting for height and weight. EP/ELBW males generally displayed more bone and soft tissue deficits than females, compared with their respective controls. Within the EP/ELBW group, early growth, male sex, height and lean mass, muscle measures, 25(OH)D levels, and BTM were independently associated with bone mineral measures, structure or strength. Young adults born EP/ELBW had evidence of impaired bone health around the age of peak bone mass compared with controls. Further follow-up of the EP/ELBW groups will determine if they have a heightened low-trauma fracture risk in later life.

Prolonged Amenorrhea and Low Hip Bone Mineral Density in Women Living With HIV-A Controlled Cross-sectional Study.

Women living with HIV (WLWH) have higher rates of prolonged secondary amenorrhea (no flow for ≥1 year) than HIV-negative women. Both having amenorrhea and being HIV positive are associated with lower areal bone mineral density (BMD). However, their combined BMD effects remain unclear. Therefore, we investigated prolonged amenorrhea and BMD in WLWH and controls. This cross-sectional study enrolled WLWH and HIV-negative control women aged 19-68 years of similar backgrounds. We assessed BMD (Hologic; as age- and ethnicity-matched Z-scores) in the Children and women: AntiRetrovirals and Markers of Aging cohort. Participants were stratified by amenorrhea history defined as past/present lack of menses for ≥1 year at age 45 and younger and not because of surgery, breastfeeding, pregnancy, or hormonal contraception. Hip and spine Z-scores by amenorrhea/no amenorrhea used linear models with multivariable analysis for relationships within WLWH. WLWH (N = 129) were similar to controls (N = 129) in age, body mass index, ethnicity, and substance use. Among WLWH, 21% experienced prolonged amenorrhea vs. 9% in controls. WLWH had significantly lower total hip (mean ± SD: -0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (-0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores than controls. Amenorrhea was independently associated with hip (P = 0.01) but not spine (P = 0.94) BMD by multivariable linear regression. WLWH with amenorrhea had lower hip Z-scores (-0.8 ± 0.9) than those without (-0.3 ± 0.8; P = 0.01). They also had higher rates of substance use, smoking, opioid therapy, hepatitis C coinfection, and lower CD4 nadir. WLWH had higher rates of prolonged amenorrhea and lower BMD than controls. WLWH with amenorrhea experienced lower hip BMD Z-scores than those without. Prolonged amenorrhea is an added osteoporosis risk in WLWH.

Real-world impact of glucocorticoid replacement therapy on bone mineral density: retrospective experience of a large single-center CAH cohort spanning 24years.

The impact of long-term and supposedly physiological doses of gluco and mineralocorticoid (GC/MC) on bone mineral density (BMD) in congenital adrenal hyperplasia (CAH) remains discordant among studies, which contain different clinical forms and corticoid regimens. Our aim was to evaluate the BMD in CAH adults receiving similar GC regimen since childhood and to correlate it with GC/MC cumulative doses. Only patients with good compliance, who used cortisone acetate (CA) during childhood and dexamethasone after the final height achievement. Cumulative GC/MC doses were calculated from diagnosis until last evaluation. BMD was analyzed by the first and last energy X-ray absorptiometry (DXA) scans performed. Twenty simple virilizing (SV) and 14 salt wasting (WS) whose mean age was 26 ± 6years, mean CA, dexamethasone, and fludrocortisone cumulative doses were 63,813 ± 32,767, 812 ± 558, and 319 ± 325mg/m2, respectively. Based on the last DXA, low BMD was observed in 11% of patients, total hip Z-score was lower in the SW than SV form (p = 0.04). Cumulative CA dose had an inverse correlation with femoral neck Z-score (p < 0.01). Total cumulative GC and MC doses had an inverse correlation with total hip Z-score (p < 0.01). In the analysis of sequential BMD during dexamethasone therapy, no association was observed among cumulative GC/MC doses, clinical forms, sex, and lumbar Z-score delta. Even though a low CA regimen during growth periods in addition to MC replacement appears to have an influence on BMD at femoral sites, interestingly a low dexamethasone one does not seem to be deleterious for bone health in adulthood.

322. Prolonged Amenorrhea Is Associated with Decreased Hip Bone Mineral Density in Women Living with HIV

BackgroundWomen living with HIV (WLWH) have higher rates of long-term amenorrhea (no flow for ≥12 months) than HIV-negative women. However, little is known about the consequences of amenorrhea for WLWH. Both amenorrhea and HIV are associated with lower areal bone mineral density (BMD); though the combined effect of both on BMD remains unclear. In this cross-sectional study we investigated whether prolonged amenorrhea adversely affects BMD among WLWH.MethodsWe investigated BMD (using a Hologic bone densitometer) and prolonged amenorrhea among WLWH and HIV-negative control women of similar socioeconomic backgrounds aged 19–68 in the CARMA cohort. Participants were stratified by HIV status and history of prolonged secondary amenorrhea defined as a self-reported absence of menses for at least one year in the past or present, occurring at age <45 years and not due to surgery, breastfeeding, pregnancy or hormonal contraception. Hip and spine Z-scores (age- and race- standardized BMD values) were compared between groups using linear models, followed by multivariable analysis of BMD-related factors.ResultsWLWH (N = 129) had significantly lower hip (mean±SD −0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (−0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores vs. controls (N = 129). Multivariable linear regression found prolonged amenorrhea was independently related to lower hip (P = 0.01), but not spine (P = 0.94) BMD. Within WLWH, the effect of amenorrhea was also additive to that of HIV, with hip Z-scores of -0.8±0.9for those with amenorrhea vs. -0.3±0.8for those normally cycling (P = 0.01). Amongst WLWH, those with prolonged amenorrhea had higher rates of illicit substance use, smoking, chronic opioid therapy, hepatitis C viral infection, and poorer HIV viral control than those with normal menstruation.ConclusionThese data suggest that WLWH having prolonged amenorrhea of ≥1 year’s duration are at increased risk for hip bone loss, a finding influenced by comorbid, HIV-associated conditions. Screening WLWH for menstrual history will allow early discovery of osteoporosis risk, and stimulate preventative measures to mitigate bone loss.Disclosures All authors: No reported disclosures.

The relationship of bone mineral density and vitamin D levels with steroid use and ambulation in patients with Duchenne muscular dystrophy.

This study aims to assess the bone mineral density (BMD) and serum levels of 25(OH)-vitamin D and their relationship with steroid use and ambulation in patients with Duchenne muscular dystrophy (DMD). Between January 2017 and May 2018, medical records of a total of 67 male patients (mean age, 13.9±4.3 years; range, 8 to 25 years) who were diagnosed with definite DMD were retrospectively analyzed. Demographic data, functional activity level, steroid use, fracture history and location, serum levels vitamin D, and lumbar and hip Z-scores in BMD at the time of the initial admission were recorded. The mean level of vitamin D was 13.4±7.5 ng/mL. In terms of serum levels of vitamin D, 28 patients (41.8%) had severe deficiency, 31 (46.3%) had insufficiency, and five patients (7.5%) had deficiency. Only three (4.5%) of the patients had sufficient levels of vitamin D. The hip Z-scores were significantly lower than lumbar Z scores. There was no significant difference in the lumbar and hip BMD measurements between the patients with and without steroid use. Lumbar Z-scores were significantly lower in non-ambulatory patients than ambulatory patients. It is of utmost importance to evaluate the initial serum vitamin D levels in terms of bone health and prescribe replacement in case of deficiency/insufficiency in DMD patients. Since the decrease in the BMD is evident in this patient population, maintaining the mobilization as long as possible, providing loading on the bone for a long time, may be beneficial.