Bone Mineral Density Z-score Research Articles

Unveiling the Metabolic Challenges in Pulmonary Arterial Hypertension: Insights into Thyroid, Glycemic, Lipid, and Bone Disorders

This study aimed to evaluate the prevalence of thyroid, glycemic, lipid and metabolic bone disorders among adult patients with pulmonary arterial hypertension (PAH). MethodsThis was an observational cross-sectional clinical study with patients with PAH, matched by sex and age with a control group without PAH. All individuals were enrolled into a clinical assessment, metabolic workup, thyroid ultrasound, and bone densitometry protocol. ResultsThe PAH group included 35 participants (34 females, 46 ± 15.5 years), and the control group, 40 (39 females, 41.8 ± 13.1 years). There was no difference in body mass index (BMI) between PAH and control group (27.5 ± 5.9 and 26.9 ± 4.3 kg/m2, respectively; p = 0.63; 95% CI = -1.8, 2.94), neither in physical activity time per week (60.3 ± 103.3, 98.9 ±137.6, respectively; p = 0.17; 95% CI = -95.23, 18.06). Although there was no difference in the prevalence of insulin resistance between the PAH (51.4%) and the control group (47.5%), p=0.74, patients with PAH had a higher median of glycated hemoglobin (A1c) than the control group (6.1% and 5.57%, respectively), p=0.006; 95% CI = -0.14, 1.22. PAH group presented lower mean total cholesterol (170.46 ± 35.51 mg/dL) and median LDL-cholesterol [105 (46) mg/dL, median (interquartile range)] levels than the control group [192.1 ± 34.44 mg/dL, p = 0.009; 95% CI = -37.76, 5.52; 121.6 (35.02) mg/dL, p=0.012; 95% CI = -34.08, 0.77, respectively]. It was found a higher prevalence of hypothyroidism (22.9%) in PAH group than in control group (2.5%), p = 0.007. We found hyperparathyroidism (HPT) among 8 patients of PAH group (23%), but none in the control group. Considering bone mineral density disorders, 12 patients from PAH group presented low bone mass, osteopenia, or osteoporosis (34%), and 8 individuals in the control group (20%), p =0.032, which represented a 2.13 higher relative risk for those conditions for the former group. The patients with HPT presented a higher creatinine level (0.98 ± 0.12 mg/dL) than the PAH patients with normal parathyroid hormone (0.76 ± 0.14 mg/dL), p = 0.0004; 95% CI = 0.12, 0.33. The PAH group also presented lower total hip (-0.15 ± 1.25) and femoral neck (-0.14 ± 1.07) bone mineral density (BMD) Z-scores than the control group (0.50 ± 1.13, p = 0.021; 95% CI = -0.18, -0.027; 0.35 ± 0.94, p = 0.038; 95% CI = -0.16, -0.01, respectively). ConclusionIn this cohort, the findings of higher A1c levels, hypothyroidism prevalence, lower LDL and total cholesterol levels, and a higher prevalence of hyperparathyroidism, as well as lower total hip and femoral neck BMD Z-scores in the PAH group, compared to the control group and highlighting the dysregulation of various metabolic pathways in patients with HAP, suggesting the need for targeted interventions to enhance patient care. Additionally, they underscore the importance of gaining a deeper understanding of the mechanisms driving these changes and their potential pathophysiological connections to the disease.

Glycogen Storage Disease Type I and Bone: Clinical and Cellular Characterization.

Glycogen storage disease (GSD) is the most prevalent inherited disorder of glycogen metabolism for which no causal treatment is available. In recent years, thanks to the improved clinical management, the life expectancy of these patients extended, disclosing previously unidentified adverse conditions in other organs. In this study, we evaluated the clinical bone complications and the cellular responses in 20 patients (aged 14.1 ± 3.4years) affected by GSD type I. Fragility fractures were reported in 35% of the patients, which were older than unfractured patients. They involved appendicular skeletal segments, while no vertebral deformity was detected. 60% of the patients had a bone mineral density (BMD) "below the expected range for age", and lumbar spine (LS) BMD Z-scores positively correlated with muscle strength. Circulating mineral and bone markers showed reduction in the older subjects, with no increase in the pubertal age. Significant correlations could not be detected between circulating markers and LS BMD Z-scores, except for sclerostin levels, which also correlated with muscle strength. The osteoclasts differentiated from patients' peripheral blood mononuclear cells did not show cell-autonomous alterations. However, circulating osteoclast precursors from healthy individuals cultured in the presence of patients' sera exhibited increased osteoclastogenesis compared to control sera suggesting that GSD type I serum factors could affect osteoclast function in a non-autonomous manner. In contrast, circulating osteoprogenitors were unremarkable.

Risk Factors for Adjacent Vertebral Fractures Following Cement Vertebroplasty: The Clinical Significance of Multiple Preexisting Vertebral Compression Fractures.

A retrospective cohort study. The study retrospectively analyzed the factors associated with the development of adjacent vertebral fractures. Adjacent vertebral fractures (AVF) may occur following cement vertebroplasty, and several risk factors have been reported with controversies. A total of 123 patients, with a mean age of 79.2 years, who underwent single-level vertebroplasty were included in the investigation. We systematically collected data encompassing baseline demographics, osteoporosis parameters, surgical details, radiologic measurements, and Hounsfield unit (HU) values in the lumbar spine. Subsequently, univariable, followed by multivariable logistic regression analyses, were employed to identify the risk factors of AVFs. Thirty of 123 patients had AVFs within 6 months following vertebroplasty. The AVF group exhibited a higher percentage of multiple preexisting vertebral compression fractures (P=0.006), a greater volume of injected cement (P=0.032), and a more pronounced reduction in local kyphosis (P=0.007). Multivariable logistic regression analysis revealed multiple preexisting vertebral compression fractures and a reduction in local kyphosis exceeding 8 degrees were independent risk factors for AVFs (P=0.008 and 0.003, respectively), with odds ratios of 3.78 (95% confidence interval: 1.41-10.12) and 4.16 (95% CI: 1.65-10.50), respectively. Subgroup analysis showed that patients with multiple preexisting vertebral compression fractures (VCFs) had significantly lower bone mineral density Z-score, T-score, and HU values compared with those without preexisting VCFs (P<0.05). Conversely, there were no significant differences in T-score or HU values between patients with no VCFs and those with a single VCF. This study demonstrated that both bone strength and local alignment are key factors associated with adjacent vertebral fractures. Specifically, having multiple preexisting vertebral compression fractures and a reduction in local kyphosis exceeding 8 degrees are independent risk factors. The presence of more than one previous vertebral compression fracture serves as a significant clinical indicator of advanced bone density reduction in patients with osteoporosis, offering a quick and straightforward method for identifying high-risk patients. Patients exhibiting these risk factors should be monitored more closely for favorable clinical outcomes. Level III-retrospective nonexperimental study.

Associations of ethnicity, skin tone, and genome-wide sequencingwith bone mineral density in adolescents.

Dual-energy x-ray absorptiometry reference data designate Black and non-Black categories, as higher BMD has been documented among Black youth. We examined associations of race, skin tone, and genetic factors with bone mineral density (BMD). 557 adolescents were followed longitudinally. Exposures included race, skin tone, and principal components (PC) from genome-wide arrays. Total body BMD Z-score (BMD-Z) was the primary outcome using linear regression. 359 adolescents identified as non-Hispanic White (NHW) and 75, non-Hispanic Black (NHB). BMD-Z was higher in NHB vs. NHW (β: 0.92 units, 95% CI: 0.64, 1.19) or those with darker skin (0.79, 95% CI: 0.49, 1.08 for brown vs. medium). The first genetic PC (PC1) correlated with identification as NHB. PC1 was associated with higher BMD-Z (0.09, 95% CI: 0.06, 0.12), even after including race (0.07, 95% CI: 0.00, 0.14) or skin tone (0.10, 95% CI: 0.05, 0.15); both race (0.26, 95% CI: -0.49, 1.01 for NHB vs. NHW) and skin tone (-0.08, 95% CI: -0.59, 0.44 for brown vs. medium) no longer predicted BMD-Z after adjustment for PC1. Genetic similarity was robustly associated with BMD, prompting a reevaluation of adolescent BMD reference data to exclude the consideration of race. Current bone density reference databases include a binary assignment of patients into "Black" and "non-Black" categories, as a higher BMD has been documented among those identifying as Black compared with individuals of other racial and ethnic backgrounds. This study found genetic similarity to be more strongly associated with bone density by dual-energy x-ray absorptiometry than race or skin tone. These data emphasize a need to reevaluate how bone density measurements are interpreted, including exploring reference data that exclude the consideration of race.

Endocrine Complications in Hepatic Glycogen Storage Diseases: A Long-term Perspective.

Patients with hepatic type of glycogen storage diseases (GSDs) can manifest endocrine features such as hypoglycemia, dyslipidemia, or osteoporosis. This study aimed to investigate the long-term endocrine consequences in patients with hepatic GSDs. This study included 64 patients from 52 families with hepatic GSDs including GSD type Ia (41 patients from 37 families), Ib (3 unrelated), III (8 from 6 families), IV (one patient), and IX (11 from 5 families). All patients were genetically confirmed. Clinical and endocrine findings were retrospectively analyzed. The median age at diagnosis and current age were 2.4 years (range, 0.1-42.4 years) and 17.6 years (range, 1.0-47.8 years), respectively. The mean height SDS at diagnosis was -3.5 ± 1.4, and short stature was observed in 35.6% of patients. Patients diagnosed after the age of 3.4 years exhibited a high risk of short stature (OR = 36.1; P-value < 0.001). Among 33 patients who reached final height, 23 (69.7%) showed delayed puberty. Hypertriglyceridemia was observed in 46 patients (71.9%), whereas 25 patients (39%) had elevated low-density lipoprotein cholesterol levels during the follow-up period. Among 24 patients who underwent dual energy X-ray absorptiometry, 22 showed a low bone mineral density Z-score of -3.0 ± 1.3 at the L-spine. This study described the long-term endocrine consequences in patients with hepatic GSDs. Pediatric endocrinologists should be aware of the presenting features and long-term endocrine sequelae of GSDs to provide proper management and decrease its morbidities.

Low bone mineral density and its influencing factors in spinal muscular atrophy without disease-modifying treatment: a single-centre cross-sectional study

BackgroundChildren with spinal muscular atrophy (SMA) are at risk of low bone mineral density (BMD) and bone fragility. This study aims to assess lumbar spine BMD measured by quantitative computed tomography (QCT) and investigate influencing factors of low BMD in children with SMA without disease-modifying treatment.MethodsDemographic data, laboratory parameters, QCT data, and data on spinal radiographs were collected. A linear regression model was carried out to explore the correlations between BMD and its related factors.ResultsSixty-six patients with SMA who had complete records between July 2017 and July 2023 were analyzed, with SMA with a mean age of 5.4 years (range, 2.4–9.7 years), including type 1 in 14, type 2 in 37, and type 3 in 15. 28.8% of patients (19/66) were diagnosed with low BMD (Z-scores ≤ − 2), and the mean BMD Z-scores on QCT was − 1.5 ± 1.0. In our model, BMD Z-scores was associated with age (β=-0.153, p = 0.001). SMA phenotype and serum bone metabolism markers, such as serum phosphorus (P), alkaline phosphatase (ALP) and 25-Hydroxyvitamin D (25-OH-D) levels did not independently predict low BMD. ROC analysis showed that the age ≥ 6.3 years predicts a Z-scores ≤ -2.0 with a sensitivity of 68.4% and a specificity of 68.1%.ConclusionsLow BMD were highly prevalent in children with SMA without disease-modifying treatment in our centre. Regular monitoring of BMD is necessary for all types of SMA children, especially those aged ≥ 6.3 years.

Investigating the association between osteopenia and bowel perforation through a multicenter radiologic analysis

Anecdotal evidence from preliminary observations has noted multiple instances where osteoporosis is present in elderly patients before the clinical detection of bowel disease, even in the absence of overt gastrointestinal symptoms. However, any potential association between these conditions remains to be further investigated. This computed tomography (CT) study investigates whether patients with gastrointestinal (GI) perforation have lower bone mineral density (BMD) than age and sex matched controls. BMD was measured by drawing 3D regions of interest in the bone marrow of the L1–L3 vertebral bodies on CT scans of each of 37 GI perforations and matched controls. Spectrometric calibration of Hounsfield units to the mineral scale was performed with density measurements in the paravertebral muscles (erector spinae) and subcutaneous adipose tissue. The mean BMD of patients with GI perforation (135.9 ± 24.3 mg/ml) was significantly lower than that of controls (96.9 ± 27.5 mg/ml, p < 0.05). The calculated T-and Z-scores of bone mineral density were also significantly different between the two groups (p < 0.05 for each) and were − 2.9 (± 0.90) and − 0.8 (± 0.91) in patients with GI perforation and − 1.6 (± 0.83) and 0 (± 0.96) in the control group, respectively. The results imply that patients with gastrointestinal (GI) perforation have lower bone mineral density (BMD) than age-and sex-matched controls, posing the question whether the screening and aggressive management of osteoporosis is high-risk populations for gastrointestinal perforation can prevent gastrointestinal complications in targeted populations.

Bone mineral density determinants in adolescents and young adults with congenital adrenal hyperplasia.

The effects of long-term glucocorticoid (GC) treatment on bone mineral density (BMD) in patients with congenital adrenal hyperplasia (CAH) remain controversial. This cross-sectional study aimed to evaluate BMD in relation to genotype, growth, vitamin D status, cumulative GC doses, and other relevant factors in youths with CAH. Thirty-two patients with classical CAH (13 males; mean age 26.0 ± 7.1 years) were compared with 32 healthy controls matched by age and sex. BMD was measured using dual-energy x-ray absorptiometry, and statistical analyses, including the Mann-Whitney U-test and Spearman's correlation coefficient, were performed to evaluate differences and associations. Median whole-body and lumbar BMD Z-scores were similar between CAH patients and controls (p = 0.27 and 0.15, respectively). Low bone density was observed in 12.5% of CAH patients and 18.75% of controls (p = 0.5), and osteoporosis was confirmed in 12.5% of CAH patients and 0% of controls (p = 0.04). BMD did not correlate with cumulative GC doses, estradiol, renin, phosphate, sodium levels, or anthropometric parameters in CAH patients. There was no significant difference in BMD between severe and non-severe genotypes of CAH. However, a positive correlation was found between the whole-body BMD Z-score and growth velocity during infancy (r = 0.776, p = 0.021) in CAH patients. Vitamin D deficiency was noted in 56.25% of CAH patients, although vitamin D levels did not correlate with BMD or genotype. No history of bone fractures was reported among study participants. CAH patients are at risk of developing osteoporosis, but in this study, BMD Z-scores were not associated with cumulative GC doses. The study did not identify an association between genotype and BMD. Poor growth during infancy was linked to decreased BMD in adulthood.

Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial.

Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels. Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism. Phase 3 trial with a 26-week double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE). 21 sites across North America and Europe. 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52. All OLE participants received TransCon PTH administered once daily. Multi-component efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes (PROs) and bone mineral density (BMD). Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events (TEAEs). At week 52, 81% (63/78) met the multi-component efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. PROs showed sustained improvements in quality of life, physical functioning, and well-being. Mean BMD Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most TEAEs were mild or moderate and none led to trial discontinuation during the OLE. At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.

12455 Bone Mineral Density Improvement After Resolution Of Endogenous Cushing Syndrome

Abstract Disclosure: C. Plessias: None. N. Charoenngam: None. T. Rittiphairoj: None. T. Suenghataiphorn: None. T. Srikulmontri: None. P. Wattanachayakul: None. M. Kurt: None. Bone Mineral Density Improvement After Resolution of Endogenous Cushing Syndrome: a Meta-analysis and meta-regression Patients with endogenous Cushing syndrome (eCS) are known to have decreased bone mineral density (BMD) and are prone to fragility fractures. Treatment of eCS have been shown in multiple studies to result in improvement in BMD. However, the degree of BMD improvement after resolution of eCS remains inadequately explored due to limited sample sizes in existing studies. Through systematic review, meta-analysis, and meta-regression techniques, we aimed to identify all available evidence to evaluate BMD improvement after resolution of eCS. Potentially eligible studies were identified from the PubMed and EMBASE databases from inception to February 2024, utilizing a search strategy incorporating terms related to "Bone mineral density" and "Cushing syndrome". Eligible studies must include adult or pediatric patients diagnosed with any form of eCS, encompassing Cushing disease (CD), adrenal adenoma, mild autonomous cortisol secretion or ectopic ACTH-secreting tumors, who received treatment resulting in CS resolution. These studies must either present lumbar spine (LS) or femoral neck (FN) BMD measurements in the form of T-score, Z-score or actual BMD values before and after CS resolution, or report mean differences (MD) of BMD, or provide individual BMD data. Point estimates with corresponding standard errors were extracted from each study and combined using the generic inverse variance method. Meta-regression analysis was utilized to explore the impact of time after resolution of eCS on BMD improvement.A total of 5,085 records were identified from the databases. After systematic review, 14 studies, including a total of 386 patients, were deemed eligible for analysis. The meta-analysis demonstrated that resolution of eCS resulted in statistically significantly improvement of LS BMD (pooled MD: Z-score: +0.76, 95%CI 0.50 – 1.02, I2 76%; T-score: +0.87, 95%CI 0.55 – 1.19, I2 78%; actual BMD: +0.092 g/cm2, 95%CI 0.060 – 0.124, I2 74%) and FN BMD (pooled MD: Z-score: +0.54, 95%CI 0.32 – 0.76, I2 75%; T-score: +0.38, 95%CI 0.25 – 0.51, I2 0%; actual BMD: +0.041 g/cm2, 95%CI 0.021 – 0.062, I2 0%). The meta-regression analysis revealed a statistically significant association between follow-up time and improvements in LS T-score BMD (predicted LS T-score improvement = 0.42 + 0.062 × year, p = 0.027) and FN Z-score BMD (predicted FN Z-score improvement = 0.35 + 0.037 × year, p = 0.003), but not with LS Z-score and FN T-score.In summary, our study presents the extent of improvement in LS and FN BMD following the resolution of eCS based on all available data in the literature. These findings have clinical significance as they offer guidance for management of osteoporosis following the resolution of eCS. Presentation: 6/3/2024

6820 Assessing The Efficacy And Safety Of Setrusumab For Osteogenesis Imperfecta: Updated Phase 2 Data From The Phase 2/3 Orbit Study

Abstract Disclosure: G.S. Gottesman: Advisory Board Member; Self; Ultragenyx, Kyowa Kirin, Inc. Consulting Fee; Self; Ultragenyx. Research Investigator; Self; Alexion Pharmaceuticals, Inc., Ultragenyx. T.O. Carpenter: Advisory Board Member; Self; Ultragenyx. Consulting Fee; Self; Ultragenyx. Research Investigator; Self; Ultragenyx. M. Wallace: Advisory Board Member; Self; Ultragenyx. Consulting Fee; Self; Novosteo. P. Smith: Grant Recipient; Self; Ultragenyx. Research Investigator; Self; Ultragenyx. E.A. Imel: Consulting Fee; Self; Ultragenyx. Grant Recipient; Self; Ultragenyx. Research Investigator; Self; Ultragenyx. H. Wang: Employee; Self; Ultragenyx. Stock Owner; Self; Ultragenyx. H.M. Byers: Employee; Self; Ultragenyx. Stock Owner; Self; Ultragenyx. S. Krolczyk: Employee; Self; Ultragenyx. Stock Owner; Self; Ultragenyx. E.M. Lewiecki: Consulting Fee; Self; Amgen Inc, Radius Health, Inc. Grant Recipient; Self; Amgen Inc, Radius Health, Inc, Ultragenyx. Research Investigator; Self; Amgen Inc, Radius Health, Inc, Ultragenyx. Speaker; Self; Amgen Inc, Kyowa Kirin, Inc. Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and low bone mass with no universally accepted treatment. Setrusumab is a fully human anti-sclerostin monoclonal antibody that improved bone mineral density (BMD), bone strength, and bone turnover markers in adults with OI (ASTEROID; NCT03118570). In the ongoing Phase 2/3 Orbit study (NCT05125809), Phase 2 evaluated the efficacy and safety of setrusumab in pediatric and young-adult cohorts with OI based on PK/PD, safety, and BMD data, to determine the dosing strategy for the Phase 3 portion. Subjects with OI Types I, III, or IV, ages 5 to &amp;lt;26 years, were randomized 1:1 to receive 20 or 40 mg/kg setrusumab intravenously monthly. Six-month data as of August 2023 are presented. Twenty-four subjects (50% female, 75% &amp;lt;18 years of age) with OI Type I (n=17/24, 71%) or III/IV (n=7/24, 29%) were enrolled and randomized to receive 20 mg/kg (n=14/24) or 40 mg/kg (n=10/24) of setrusumab. The mean (SD) baseline-corrected area under the effect curve (AUEC) for serum P1NP in the 20 mg/kg setrusumab group was 4153 (4407) µg/(L*day) over month one of treatment, and 5256 (5521) µg/(L*day) in the 40 mg/kg group. Mean (SE) change from baseline in lumbar spine BMD in the 20 mg/kg group was 9.1% (1.8%) and 12.8% (2.5%) at M3 and M6, respectively (all p&amp;lt;0.05 vs baseline) and 9.3% (2.4%) and 16.1% (3.9%) in the 40 mg/kg group (M6 p&amp;lt;0.05 vs baseline). Mean (SE) baseline BMD Z-score in the 20 mg/kg group of 2.1 (0.8) improved by 0.6 (0.8) at M3 and 0.9 (0.8) at M6, and improved from 1.1 (0.4) at baseline by 0.5 (0.4) and 0.9 (0.4) at M3 and M6, respectively, in the 40 mg/kg group (all p&amp;lt;0.05 vs baseline). The median annualized fracture rate (excluding fingers, toes, face, and skull) was reduced significantly from 0.7 to 0 (p=0.042) after setrusumab initiation (calculated reduction of 67%). No new radiographically confirmed fractures excluding fingers, toes, face, and skull were reported in 20/24 (83%) subjects after starting setrusumab, while only 4/24 (17%) reported fractures (precipitating events: one subject: slipped on ice, stubbed toe, one subject each: fell off of tricycle, bending over in bed, tripped and fell). Setrusumab treatment resulted in no unexpected adverse events. Treatment-related adverse events included infusion-related reaction (7/24, 29%), headache (3/24, 13%) infusion site pain, bone pain, and upper respiratory tract infection (each 1/24, 4%). In Orbit Phase 2, we observed significant improvements from baseline in lumbar spine BMD at M3 and M6 at both 20 and 40 mg/kg doses, with no marked differences between dose groups. Fracture rates significantly decreased with setrusumab initiation, with 83% of subjects reporting no new fractures. Presentation: 6/1/2024

Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial.

Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.

Differences In BMD Z-scores Of Athletes Participating In Difference Sports Types

Differences In BMD Z-scores Of Athletes Participating In Difference Sports Types

The natural course of bone mineral density in transgender youth before medical treatment; a cross sectional study.

Bone mineral density (BMD) Z-scores decrease during puberty suppression in transgender youth. Assessment of treatment impact has been based on the assumption that without intervention, BMD Z-scores remain stable. However, the natural course of BMD in this population is unknown. Retrospective cross-sectional study. Dual-energy X-ray absorptiometry scans prior to medical intervention were included from 333 individuals assigned male at birth (AMAB) and 556 individuals assigned female at birth (AFAB) aged 12-25 years. The relationship between age and BMD Z-scores of sex assigned at birth was analysed for the lumbar spine (LS), total hip (TH), femoral neck (FN), and total-body-less-head (TBLH), adjusted for height SDS, height-adjusted lean mass Z-score, and whole body percentage fat Z-score. In individuals AMAB, the BMD Z-score was negatively associated with age between 12 and 22 years: LS -0.13/year (95% confidence interval, CI -0.17; -0.10); TH -0.05/year (95% CI -0.08; -0.02); FN -0.06/year (95% CI -0.10; -0.03); and TBLH -0.12/year (95% CI -0.15; -0.09). Adjusting for height-adjusted lean mass Z-score attenuated the association at the LS and TBLH and eliminated the association at the TH and FN. BMD Z-scores and age were not associated between 22 and 25 years. In individuals AFAB, BMD Z-scores were only associated with age at the TBLH (-0.08/year, 95% CI -0.12; -0.04) between age 12 and 20 years. In individuals AMAB aged 12-22 years prior to any treatment, BMD Z-scores were inversely correlated with age. This could imply that BMD increases less in individuals AMAB than in the general population, and that changes in Z-score during puberty suppression and subsequent hormone supplementation are not necessarily due to treatment, but possibly related to lifestyle factors.

Bone Accrual Trajectories in Children and Adolescents with Perinatal HIV Infection.

Low bone mineral density (BMD) has been reported in children and adolescents living with perinatally-acquired HIV (PHIV). Little is known about their bone accrual through puberty compared to an uninfected healthy cohort. To compare bone accrual in PHIV and healthy children. PHIV children aged 7-16 years had dual energy X-ray absorptiometry (DXA) at entry, 2 years, and then at least 2 years later. Bone accrual was compared to healthy children from the Bone Mineral Density in Childhood Study (BMDCS). United States academic clinical research centers. 172 PHIV; 1321 BMDCS. We calculated height-adjusted whole-body and spine BMD and bone mineral content (BMC) Z-scores in PHIV using BMDCS reference curves. We fit piecewise weighted linear mixed effects models with change points at 11 and 15 years, adjusted for age, sex, race, height Z-score, and Tanner stage, to compare BMD and BMC Z-scores across actual age by cohort.Main Outcome Measure: BMD/BMC Z-scores. Height-adjusted whole-body BMD and BMC Z-scores in PHIV were lower across age compared to BMDCS children. Spine BMD Z-score across age was higher in PHIV after height adjustment. Whole-body and spine bone area tended to be lower in PHIV. PHIV had slower accrual in whole-body and spine bone area before 14 years. After 15 years, bone area accruals were similar, as were height-adjusted spine BMC Z-scores, across age. PHIV had persistent deficits in all measures except height-adjusted spine BMD and BMC Z-scores. Data are needed on PHIV followed to adulthood.

The Impact of Diet on Body Composition in a Cohort of Pediatric and Adult Patients with Maple Syrup Urine Disease.

The treatment for Maple Syrup Urine Disease (MSUD) consists of a hypoproteic diet with integration therapy to limit leucine intake, ensuring adequate energy, macronutrients, and micronutrients to prevent catabolism and promote anabolism. We conducted a retrospective cross-sectional study at the Metabolic Rare Disease Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. Patients with MSUD who were over 3 years old, not treated with liver transplantation, and who provided written consent, were included. The study aimed to describe the dietary treatment of patients with MSUD, evaluate growth data, and analyze the effect of a low-protein and semi-synthetic diet on body composition. Data on height, weight, BMI, waist circumference, food intake, physical activity, and DEXA scans were collected. Thirteen subjects (11 classic MSUD, 2 intermediate MSUD) were included, of which 5 < 18 years old. Results indicated that patients with MSUD follow a balanced diet and have body compositions like healthy subjects in terms of fat and lean mass. A high incidence of osteopenia was observed from a young age, with a positive correlation between protein intake and lean mass and a negative correlation between BCAA-free mixture consumption and bone mineral density z-score. The study highlights the positive effects and potential consequences of the semi-synthetic diet on the body composition of patients with MSUD. A similar study involving all Italian metabolic centers treating MSUD is recommended.

Description of bone health in adolescents and young persons with Klinefelter syndrome – results from a pilot study

BackgroundIn adults with Klinefelter syndrome (KS), impaired bone health with reduced bone mineral density (BMD) has been described even in the presence of testosterone replacement therapy. The aim of the present study was to characterize bone health in young patients with KS.Patients and methods20 participants aged 16.10 ± 4.28 years with KS (7 with testosterone replacement therapy) were included in the KliBONE study (DRKS 00024870). Medical history, clinical, radiographic and biochemical parameters of bone health and metabolism were obtained. Radiographic bone health index (BHI) was assessed via automated digital X-ray radiogrammetry of the left hand or via dual energy X-ray absorptiometry (DXA) of the lumbar spine and left femur in participants ≥ 16 years. Peripheral blood mononuclear cells were differentiated into osteoclasts and quantified in 7 participants and 7 healthy controls.ResultsMean BHI SDS was − 1.42 ± 1.22 and mean BMD z-score at the lumbar vertebrae (L1-4) was − 0.92 ± 1.00. 25-OH-vitamin D levels < 20 ng/ml were detected in 8/20. Other parameters of bone metabolism (bone-specific alkaline phosphatase, PTH, ß-crosslaps and osteocalcin) were within age-appropriate reference ranges. Serum leptin SDS was elevated (mean 2.15 ± 1.19). The number of osteoclasts in participants with KS did not differ from that of controls.ConclusionBHI SDS and BMD z-scores were lower than expected in young individuals with KS despite age-appropriate bone turnover markers and no apparent pathology in osteoclast differentiation. The cause of the early-onset bone phenotype requires further investigation.

A causal relationship between bone mineral density and breast cancer risk: a mendelian randomization study based on east Asian population

BackgroundBreast cancer (BC) poses significant burdens on women globally. While past research suggests a potential link between bone mineral density (BMD) and BC risk, findings remain inconsistent. Our study aims to elucidate the causal relationship between BMD and BC in East Asians using bidirectional Mendelian randomization (MR).MethodsGenetic association data for bone mineral density T-scores (BMD-T) and Z-scores (BMD-Z) (Sample size = 92,615) and BC from two different sources (Sample size1 = 98,283; Sample size2 = 79,550) were collected from publicly available genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with BMD-T and BMD-Z as phenotype-related instrumental variables (IVs) were used, with BC as the outcome. As the primary means of causal inference, the inverse variance weighted (IVW) approach was employed. Heterogeneity analysis was conducted using Cochran’s Q test, while MR-Egger regression analysis was implemented to assess the pleiotropic effects of the IVs. Sensitivity analyses were performed using methods such as MR-Egger, weighted median, and weighted mode to analyze the robustness and reliability of the results. The MR-PRESSO method and the RadialMR were used to detect and remove outliers. The PhenoScanner V2 website was utilized to exclude confounding factors shared between BMD and BC. Besides, the Bonferroni correction was also used to adjust the significance threshold. Then, the meta-analysis method was applied to combine the MR analysis results from the two BC sources. Finally, a reverse MR analysis was conducted.ResultsThe results of the IVW method were consolidated through meta-analysis, revealing a positive correlation between genetically predicted BMD-T (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:OR\\:=\\:1.22$$\\end{document}, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:95\\%\\:CI:\\:1.13-1.33$$\\end{document}, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:P<0.001$$\\end{document}) and BMD-Z (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:OR\\:=\\:1.17$$\\end{document},\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:95\\%\\:CI:\\:1.09-1.26$$\\end{document}, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:P<0.001$$\\end{document}) with increased BC risk. The Cochran’s \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:Q$$\\end{document} test and MR-Egger regression suggested that neither of these causal relationships was affected by heterogeneity or horizontal pleiotropy. The sensitivity analyses supported the IVW results, indicating the robustness of the findings. Reverse MR analysis showed no causal relationship between BC and BMD.ConclusionOur MR study results provide evidence for the causal relationship between BMD and BC risk in East Asian populations, suggesting that BMD screening is of great significance in detecting and preventing BC.

Meta-analysis of bone mineral density in adults with phenylketonuria

BackgroundLifelong management of phenylketonuria (PKU) centers on medical nutrition therapy, including dietary phenylalanine (Phe) restriction in addition to Phe-free or low-Phe medical foods/protein substitutes. Studies have reported low bone mineral density (BMD) in mixed-age PKU populations, possibly related to long-term Phe restriction. Therefore, a meta-analysis investigating BMD specifically in adults with PKU was conducted.MethodsStudies reporting BMD-related outcomes were identified from a systematic literature review evaluating somatic comorbidities experienced by adults with PKU on a Phe-restricted diet (searched February 1, 2022, updated November 1, 2023). Risk of study bias was assessed (Scottish Intercollegiate Guidelines Network checklists). The primary outcome of the meta-analysis was pooled mean BMD Z-scores of different bones. Secondary outcomes were the prevalence of low BMD Z-scores at pre-specified thresholds. Subgroup analyses of mean BMD Z-scores (decade of study publication, controlled versus uncontrolled blood Phe levels, gender) were conducted.ResultsBMD-related data from 4097 individuals across 10 studies rated as at least acceptable quality were included. Mean BMD Z-scores were statistically significantly lower compared with an age-matched control or reference (non-PKU) population, across bones, but still within the expected range for age (> -2.0): lumbar spine (seven studies, n = 304), -0.63 (95% confidence interval (CI): -0.74, -0.52); femoral neck (four studies, n = 170), -0.74 (95% CI: -1.25, -0.22); radius (three studies, n = 114), -0.77 (95% CI: -1.21, -0.32); total body (four studies, n = 157), -0.61 (95% CI: -0.77, -0.45). The small number of observations in the subgroup analyses resulted in a high degree of uncertainty, limiting interpretation. Estimated prevalence of BMD Z-scores ≤ -2.0 was 8% (95% CI: 5%, 13%; four studies, n = 221) and < -1.0 was 42% (95% CI: 35%, 51%; five studies, n = 144).ConclusionsAdults with PKU had lower BMD Z-scores than the reference (non-PKU) population but < 1 in 10 were below the expected range for age. The low number of studies prevents identification of which population characteristics are most impacting BMD.This meta-analysis was supported by BioMarin Pharmaceutical Inc., Novato, CA and is registered with the Research Registry (reviewregistry1476).

Follicle-stimulating hormone receptor gene polymorphisms influence Body Mass Index, metabolism, and bone mineral density in postmenopausal women.

Covering a significant part of a woman's life, the postmenopausal phase is often associated with the onset of obesity, metabolic dysfunction, osteoporosis, and their most disabling complications. In this context, scant evidence from both preclinical and clinical studies suggests that single nucleotide polymorphisms (SNPs) of the follicle-stimulating hormone receptor (FSHR) gene might be involved in the etiopathogenesis of these conditions, posing them as possible molecular predictors of their development. Therefore, this study aimed to evaluate the role of the FSHR gene SNPs c.2039A>G and c.-29 G>A on Body Mass Index (BMI), metabolic parameters, and bone metabolism in postmenopausal women. To achieve this goal, 49 postmenopausal Caucasian women aged from 45 to 80 years and with no factors known to influence metabolism and/or bone mineral density (BMD) were enrolled and assessed for their medical history, medical family history, anthropometric parameters and hormonal, metabolic and lipid profiles, and BMD. Then, they were genotyped for the FSHR gene SNPs c.2039A>G and c.-29G>A. Finally, the resulting data were classified according to woman's genotypes and subjected to statistical analysis. No significant differences were found between the distributions of most endpoint parameters examined by genotype. However, none of the women with the c.2039A>G FSHR GG gene SNP were affected by obesity and had the highest lumbar BMD z-score within the cohort. Additionally, those with the FSHR c.-29G>A AA genotype had the lowest serum glucose levels. This preliminary study suggests that the FSHR c.2039A>G GG SNP, which is associated with reduced sensitivity of the FSHR, may have a protective role against obesity, offering further evidence for the possible association among FSH, FSHR polymorphisms, and insulin metabolism.