Forearm Bone Mineral Density Research Articles

Effect of androgen deprivation therapy on bone mineral density in patients with prostate cancer.

Objectives:To access the effects of acute and chronic Androgen Deprivation Therapy on Bone Marrow Density and related bone markers; to compare the bone loss among the patients who terminated GnRH use and control group (not given ADP therapy at all) with the ones with acute or chronic Androgen Deprivation Therapy.Methods:A cross-sectional study was conducted in the Oncology Department of Nishtar Medical University & Hospital Multan for one year. Bone mineral density of the entire body, 1/3rd distal radius, ultra-distal forearm, femoral neck, and lumbar spine, was measured in 40 patients diagnosed with non-metastatic prostate cancer at baseline for the duration of six months. They were categorized into four groups: (i) acute ADT (less than six months of treatment; (ii) chronic ADT (greater than six months of treatment; (iii) former ADT; and (iv) no ADT (placebo groups). Quantitative measures of bone metabolism marker, including C-terminal cross-linking telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) was done.Results:The cross-sectional analysis showed that BMD dropped significantly in more in patients with former ADT or control groups as compared to chronic ADT. At the 6th month assessment, a significant decline in ultra-distal forearm BMD was demonstrated in patients from both acute and chronic ADT groups (4.05% and 2.54%, P = .001 and .016, respectively). Total body BMD was significantly reduced among those on acute treatment (2.91%, p=0.022). In the former ADT group, a significant increase of BMD was observed in the femoral neck and lumbar spine bones (1.60 % and 2.85%, P = .001 and .0064, respectively). The difference of changes in BMD of the acute and chronic groups was not significant. The levels of PINP and CTX levels were significantly increased in an chronic and acute group than in placebo or former ADT groups.Conclusion:Chronic and acute ADT users experience similar changes in BMD levels but reversibility of BMD can be achieved on withdrawal of treatment. Similarly disturbed bone metabolism markers come back in range on withdrawal of treatment.

Downturn in Childhood Bone Mass: A Cross-Sectional Study Over Four Decades.

ABSTRACTScreen time and physical inactivity have increased among children. As physical activity is a determinant of bone mass, there is a concern that children today have lower bone mass than earlier. If this is true, fractures may become more common in the future. In 2017–2018, we used single‐photon absorptiometry (SPA) to measure distal forearm bone mineral density (BMD; mg/cm2) in a normative cohort of 238 boys and 204 girls aged 7 to 15 years. We compared these results to BMD in a normative cohort collected in 1979–1981 (55 boys and 61 girls aged 7 to 15 years) measured by the same scanner. To investigate difference between the two cohorts, we used multiple linear regression with age, sex, and cohort as predictors. Predicted bone density at age 16 years was estimated through the slope values. The bone density‐age slope was flatter in the cohort measured in 2017–2018 than in the cohort measured 1979–1981 (−5.6 mg/cm2/yr [95% confidence interval −9.6 to −1.5]). Predicted bone density was at age 16 years in 2017–2018 in boys was 10% lower (−0.9 SD) and in girls 11% lower (−1.1 SD) than in their counterparts measured in 1979–1981. We found indications that children nowadays develop lower bone mass than four decades ago, giving concern that they may have a higher risk of osteoporosis and fragility fractures as they grow old. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Reduction in femoral neck and total hip bone mineral density following hospitalisation for diabetes-related foot ulceration

Management of diabetes-related foot ulceration (DFU) includes pressure offloading resulting in a period of reduced activity. The metabolic effects of this are unknown. This study aims to investigate changes in bone mineral density (BMD) and body composition 12 weeks after hospitalisation for DFU. A longitudinal, prospective, observational study of 22 people hospitalised for DFU was conducted. Total body, lumbar spine, hip and forearm BMD, and total lean and fat mass were measured by dual-energy X-ray absorptiometry (DXA) during and 12 weeks after hospitalisation for DFU. Significant losses in total hip BMD of the ipsilateral limb (− 1.7%, p < 0.001), total hip BMD of the contralateral limb (− 1.4%, p = 0.005), femoral neck BMD of the ipsilateral limb (− 2.8%, p < 0.001) and femoral neck BMD of the contralateral limb (− 2.2%, p = 0.008) were observed after 12 weeks. Lumbar spine and forearm BMD were unchanged. HbA1c improved from 75 mmol/mol (9.2%) to 64 mmol/mol (8.0%) (p = 0.002). No significant changes to lean and fat mass were demonstrated. Total hip and femoral neck BMD decreased bilaterally 12 weeks after hospitalisation for DFU. Future research is required to confirm the persistence and clinical implications of these losses.

Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study.

Background: We aimed at investigating causal associations between matrix metalloproteinases (MMPs) and bone mineral density (BMD) by the Mendelian randomization (MR) analysis. Methods: From genome-wide association studies of European ancestry, we selected instrumental variables for MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, and MMP-12. Accordingly, we retrieved summary statistics of three site-specific BMD, namely, forearm, femoral neck, and lumbar spine. We conducted an inverse variance weighted MR as the primary method to compute overall effects from multiple instruments, while additional MR approaches and sensitivity analyses were implemented. Bonferroni-adjusted significance threshold was set at p < 0.05/18 = 0.003. Results: Totally, there was no evidence for causal effects of genetically-predicted levels of MMPs on BMD measurement at three common sites. MR results indicated that there were no causal associations of circulating MMPs with forearm BMD (all p ≥ 0.023) by the inverse variance weighted method. Similarly, there were no causal effects of MMPs on femoral neck BMD (all p ≥ 0.120) and MR results did not support causal relationships between MMPs and lumbar spine BMD (all p ≥ 0.017). Multiple sensitivity analyses suggested the robustness of MR results, which were less likely to be biased by unbalanced pleiotropy or evident heterogeneity. Conclusion: We found no evidence for the causal relationship between MMPs and BMD in the European population.

The association between hemoglobin level and osteoporosis in a Chinese population with environmental lead and cadmium exposure.

Low hemoglobin (Hb) level or anemia is associated with osteoporosis and bone fracture. Cadmium (Cd) and lead (Pb) exposure are also risk factors of osteoporosis and anemia. However, the role of anemia in Cd/Pb related bone loss remains unclear. The aim of present study was to investigate the association between Hb level and bone loss in a population with environmental lead and cadmium exposure. One hundred and ninety-four women and 108 men with different levels of Cd/Pb exposure were included in our study. The Cd/Pb exposure was determined using graphite-furnace atomic absorption spectrometry. Forearm bone mineral density (BMD) was determined by peripheral dual-energy X-ray absortiometry. Hb concentration was determined using an automatic blood cellcounter. A logistic model was established to predict the risk of osteoporosis. The BMDs of women that had the highest quartile BCd and BPb were markedly lower than that with the lowest quartile (p < 0.05). The BMD and the prevalence of osteoporosis in men with anemia were lower and higher than that with normal Hb (p < 0.05), respectively. In men, age, BPb and anemia were independent risk factors for osteoporosis. The odds ratio (OR) of men with anemia was 11.28 (95%confidence interval (CI):1.94-65.54) and 19.56 (95%CI: 2.98-128.78) compared to those with normal Hb after adjusting for potential cofounders. No such association was found in women. The area under the curve was 0.88 (95%CI: 0.82-0.96) in predicting osteoporosis using the logistic model in men. Linear discriminant analysis also showed that 90.7% of osteoporosis was correctly classified. Our data show that anemia is associated with incident of osteoporosis in men but not in women that environmentally exposed to Pb and Cd.

Measuring forearm bone density instead of lumbar spine bone density improves the sensitivity of diagnosing osteoporosis in older adults with cardiovascular diseases: Data from SARCOS study

IntroductionIn older individuals with cardiovascular diseases, it has been challenging to diagnose osteoporosis due to aortic calcification and degenerative processes in the spine of older adults, especially in very old adults. AimTo assess whether the distal forearm BMD with the proximal femur BMD has greater sensitivity for the diagnosis of osteoporosis than the lumbar spine BMD with the proximal femur BMD. MethodsWe evaluated 515 older adults with cardiovascular disease from the SARCOS study and stratified them into under and over 80-year-old age groups and according to gender. Two diagnostic criteria were used to assess osteoporosis, SPF (lumbar spine and proximal femur BMD) and DFF (distal forearm and proximal femur BMD), which were compared with the multiple bone sites (MS) criteria (lumbar spine, distal radius, femoral neck, and total femur BMD). Results43.9% were aged ≥80 years. Osteoporosis by SPF was diagnosed in 34% (n = 175), by DFF in 42.2% (n = 216), and by MS in 46.8% (n = 241). The characteristics of the three groups were similar. For every 100 older individuals with osteoporosis based on MS, 27 were not diagnosed by the SPF, and nine were not diagnosed by DFF (p = 0.001). The SPF did not diagnose osteoporosis in 23/100 in older adults aged <80 years, while DFF did not diagnose 16/100 (p.ns). In adults aged ≥80 years, the SPF did not identify osteoporosis in 31/100 older adults, while the DFF failed to identify it in only 5/100 (p < 0.001). In men and women aged ≥80 years, DFF showed higher sensitivity for the diagnosis of osteoporosis compared to the SPF criterion. ConclusionIn the elderly population with cardiovascular disease evaluated in our study, the use of distal forearm BMD instead of lumbar spine BMD, associated with proximal femur BMD, showed higher sensitivity for the diagnosis of osteoporosis, regardless of gender, and especially among the very older adults.

Identifying periods of susceptibility to perfluoroalkyl substances and bone mineral density in early adolescence: the HOME Study

BACKGROUND AND AIM: Perfluoroalkyl substance (PFAS) exposures may affect childhood bone mineral density (BMD), but no studies have assessed periods of heightened susceptibility. We estimated associations of individual PFAS and their mixture during gestation and three times during childhood with BMD in early adolescence. METHODS: We examined 222 mother-child pairs enrolled in a prospective pregnancy and birth cohort in Cincinnati, OH from 2003-2006. We measured concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid, perfluorohexanesulfonic acid, and perfluorooctanesulfonic acid in maternal serum collected at 16 weeks gestation and child serum collected at age 3, 8, and 12 years. At age 12 years, we measured areal BMD at six skeletal sites with dual x-ray absorptiometry and calculated height-, age-, sex-, and population ancestry-specific BMD Z-scores. Using linear regression, we estimated covariate-adjusted differences in BMD Z-scores per doubling of PFAS concentrations at each period. Using hierarchical Bayesian kernel machine regression (hBKMR), we estimated period-specific associations and posterior inclusion probabilities (PIPs) to determine periods of heightened susceptibility to PFAS mixtures. RESULTS:Associations were strongest for PFOA and forearm (1/3 distal radius) BMD, with differing periods of susceptibility for males and females. Among males, forearm BMD Z-score differences (95% confidence interval) per doubling of PFOA were -0.26 (-0.50, -0.02), -0.33 (-0.68, 0.02), -0.24 (-0.61, 0.13), and -0.00 (-0.30, 0.29) for gestation and ages 3, 8, and 12, respectively. Among females, the corresponding estimates were -0.12 (-0.38, 0.15), -0.07 (-0.44, 0.30), -0.30 (-0.76, 0.17), and -0.44 (-0.81, -0.07). Patterns were generally similar but weaker for other PFAS and skeletal sites. Period-specific PIPs from hBKMR models were highest for the PFAS mixture at age 8 for males (0.76) and age 12 for females (0.62). CONCLUSIONS:PFOA and PFAS mixtures were associated with lower BMD in early adolescence. Susceptibility to PFAS may occur earlier in life for males compared with females. KEYWORDS: Chemical exposures, Children's environmental health, Mixtures analysis, PFAS, Endocrine disrupting chemicals, Environmental epidemiology

Causal Effect of Blood Pressure on Bone Mineral Density and Fracture: A Mendelian Randomization Study.

BackgroundHypertension may have some association with osteoporosis. This Mendelian randomization (MR) study aimed to explore the causal effect of blood pressure (BP) on bone mineral density (BMD), fall, and fracture.MethodsWe used the genome-wide association study (GWAS) summary data among 330,956 European-descent individuals to identify 107 single-nucleotide polymorphisms (SNPs) as the instrumental variables of BP. MR analyses of these instruments were performed on 53,236 European individuals for the association with forearm BMD (FA-BMD), femoral neck BMD (FN-BMD), and lumbar spine BMD (LS-BMD); 451,179 European individuals for fall susceptibility; and up to 1.2 million individuals from European descent for fracture. Conventional inverse variance weighted (IVW) method was adopted to obtain the causal estimates of BP on different outcomes, while weighted median, MR-egger, and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used for sensitivity analyses.ResultsGenetically high pulse pressure (PP) could significantly improve FA-BMD (beta-estimate: 0.038, 95% confidence interval [CI]: 0.013 to 0.063, SE:0.013, P-value=0.003<Bonferroni correction P) in the IVW analysis, indicating that 1-SD increase in PP was associated with the improvement in FA-BMD levels by 0.038 g/cm2 (95% CI: 0.013 to 0.063). This positive finding was also confirmed by weighted-median analysis (beta-estimate: 0.034, 95% CI: 0.000 to 0.067, SE:0.017, P-value=0.046) and MR-Egger analysis (beta-estimate: 0.117, 95% CI: 0.026 to 0.208, SE:0.046, P-value=0.011). However, there was no remarkable MR association between BP and other outcomes (i.e., FN-BMD, LS-BMD, fall, and fracture).ConclusionsOur findings reveal a potentially causal relationship between high PP and improved FA-BMD, which may provide new sights for the treatment of osteoporosis.

Depression and Osteoporosis: A Mendelian Randomization Study

Observational studies suggest a link between depression and osteoporosis, but these may be subject to confounding and reverse causality. In this two-sample Mendelian randomization analysis, we included the large meta-analysis of genome-wide association studies for depression among 807,553 individuals (246,363 cases and 561,190 controls) of European descent, the large meta-analysis to identify genetic variants associated with femoral neck bone mineral density (FN-BMD), forearm BMD (FA-BMD) and lumbar spine BMD (LS-BMD) among 53,236 individuals of European ancestry, and the GWAS summary data of heel BMD (HE-BMD) and fracture among 426,824 individuals of European ancestry. The results revealed that genetic predisposition towards depression showed no causal effect on FA-BMD (beta-estimate: 0.091, 95% confidence interval [CI] − 0.088 to 0.269, SE:0.091, P value = 0.320), FN-BMD (beta-estimate: 0.066, 95% CI − 0.016 to 0.148, SE:0.042, P value = 0.113), LS-BMD (beta-estimate: 0.074, 95% CI − 0.029 to 0.177, SE:0.052, P value = 0.159), HE-BMD (beta-estimate: 0.009, 95% CI − 0.043 to 0.061, SE:0.027, P value = 0.727), or fracture (beta-estimate: 0.008, 95% CI − 0.071 to 0.087, SE:0.041, P value = 0.844). These results were also confirmed by multiple sensitivity analyses. Contrary to the findings of observational studies, our results do not reveal a causal role of depression in osteoporosis or fracture.

Marine n-3 Polyunsaturated Fatty Acids and Bone Mineral Density in Kidney Transplant Recipients: A Randomized, Placebo-Controlled Trial.

Kidney transplant recipients are at high risk of progressive bone loss and low-energy fractures in the years following transplantation. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation may have beneficial effects on bone strength. The Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial was an investigator initiated, randomized, placebo-controlled trial investigating the effects of marine n-3 PUFA supplementation after kidney transplantation. Effects of supplementation on bone mineral density (BMD) and calcium metabolism were pre-defined secondary endpoints. Adult kidney transplant recipients (n = 132) were randomized to 2.6 g marine n-3 PUFA supplement or olive oil (control) from 8 to 52 weeks post-transplant. Dual energy X-ray absorptiometry was performed to assess changes in bone mineral density of hip, spine, and forearm, as well as trabecular bone score (TBS) of the lumbar spine. Student’s t test was used to assess between-group differences. There were no differences in ΔBMD between the two groups (intervention vs. control) at lumbar spine (−0.020 ± 0.08 vs. −0.007 ± 0.07 g/cm², p = 0.34), total hip (0.001 ± 0.03 vs. −0.005 ± 0.04, p = 0.38), or other skeletal sites in the intention-to-treat analyses. There was no difference in the change in TBS score (0.001 ± 0.096 vs. 0.009 ± 0.102, p = 0.62). Finally, no effect on biochemical parameters of mineral metabolism was seen. Results were similar when analyzed per protocol. In conclusion, we found no significant effect of 44 weeks of supplementation with 2.6 g of marine n-3 PUFA on BMD in kidney transplant recipients.

Low Bone Mineral Density and Recurrent Fractures During and After Pregnancy: Dilemma of an Overlooked Diagnosis

Background: Decreased bone mineral density (BMD) during pregnancy and lactation are rarely described in literature. We present this case of multiple compression fractures during and after pregnancy, highlighting the diagnostic and therapeutic dilemma of an overlooked diagnosis. Clinical Case: A 23-year-old female without significant past medical history, suffers from an acute onset lower back pain in the third trimester of her first pregnancy. On initial evaluation, this back pain was thought to be musculoskeletal and was dismissed by her medical team. No imaging was ordered throughout the duration of pregnancy, despite the pain remaining unrelenting. On her second day post-partum, she heard a “pop” in her back and fell while holding her newborn. Imaging revealed multiple vertebral compression fractures, in different stages of acuity. Due to debilitating pain, the patient quit breastfeeding and ultimately would never hold her baby again. Her simple activities of daily living were stymied, both as a mother and secretary. It wasn’t long before she couldn’t even fax forms in her office and had to leave work with debility. Traumatized by these life events and continuing to be afflicted by this chronic pain, the patient decided against having any future children. Her compression fractures were managed with different types of analgesics in addition to vitamin D and calcium supplements.At age 53 and 57, BMD scans showed a T-score >1 at both the lumbar spine and total hip. Forearm BMD was not evaluated at these times. At age 58, a CT spine demonstrated new compression fractures at T5-T12 & L1-L5. She subsequently underwent kyphoplasty of T5, T7 and T8. Fortunately, a bone core biopsy of these 3 vertebrae showed no malignant pathology. A follow up CT scan 6 months later showed stable compression fractures, along with multilevel degenerative changes and neural foraminal stenosis. At age 60, the patient would receive L4-L5 trans-foraminal epidural corticosteroid injection and referral to the bone clinic at a tertiary health center. Initial lab work on referral was significant for normal calcium, albumin, parathyroid hormone, vitamin D, kidney function, liver function, serum and urine protein electrophoresis and cross link N-telopeptide. Osteocalcin was low at 3.9 ng/mL (NL 8.8–37.6 ng/mL). Repeat BMD scan showed T-scores of 0.6, 1.1 and -2.6 at her lumbar spine, total hip and distal forearm respectively. Her osteoporosis is currently managed with teriparatide without active issues. Conclusion: This case highlights the rare development of low BMD in pregnant and breastfeeding women, without prior risk factors, jeopardizing future quality of life. The evidence behind the incidence and pathophysiology underlying these changes remains deficient. There remains a dearth of guidelines for definition and treatment of osteoporosis and low BMD in young peripartum women.

Anti-Mullerian hormone was a serum biomarker for early knee osteoarthritis - Iwaki cohort study

Anti-Mullerian hormone was a serum biomarker for early knee osteoarthritis - Iwaki cohort study

Causal effects of homocysteine levels on the changes of bone mineral density and risk for bone fracture: A two-sample mendelian randomization study

Observational studies have demonstrated the relations of homocysteine (HCY) with bone mineral density (BMD) and bone fracture risk, but yielding contradictory results. The present study was conducted to evaluate whether the genetically predicted plasma HCY levels were causally associated with the change of BMD and the risk of bone fracture. Genetic summary statistics were extracted from genome-wide association study (GWAS) meta-analysis of plasma HCY levels (n=44,147), GWAS meta-analyses of measured forearm (FA), femoral neck (FN) and lumbar spine (LS) BMD (n=up to 32,735), UK Biobank estimated heel BMD (eBMD) (n=426,824) and fracture (n=426,795) GWAS data. Two Sample Mendelian Randomization (TSMR) analysis was performed to assess the causal effects of genetically determined plasma HCY on the BMD and bone fractures. The MR analysis indicated that, genetically decreased plasma HCY was associated with the increased FA-BMD based on the inverse variance weighting (IVW) method (standard deviation [SD]=0.348, 95% CI: 0.146 to 0.550, P=7×10-4). However, there were no significant associations of genetically decreased plasma HCY with FN-BMD, LS-BMD, eBMD and the risk for bone fracture (SD=-0.041, 95% CI:-0.189 to 0.106, P=0.582; SD=-0.053, 95% CI:-0.238 to 0.131, P=0.572; SD=-0.030, 95% CI:-0.090 to 0.030, P=0.328, odds ratio [OR]: 1.03, 95% CI: 0.94 to 1.13, P=0.562, respectively). Moreover, the results also found that genetically determined HCY increase was not correlated with the changes of BMD and the risk for bone fracture. Our study revealed that genetically decreased plasma HCY was associated with increase of FA-BMD.

Relationship between Serum Nutritional Factors and Bone Mineral Density: A Mendelian Randomization Study.

Multiple risk factors have been implicated in the development of osteoporosis. This study examined potential associations between serum nutritional factors and bone mineral density (BMD). Six nutritional factors were selected as exposures. Outcomes included total body BMD (n = 66 945); BMD at the forearm (FA), femoral neck (FN) and lumbar spine (LS) (n = 8143, n = 32 735, and n = 28 498, respectively); estimated heel BMD (HL eBMD) (n = 394 929); and HL eBMD stratified by sex (n = 206 496). A 2-sample Mendelian randomization approach was adopted to estimate the association between serum nutritional factors and BMD. The threshold for adjusted P value was 1.39 × 10-3. Serum calcium levels were inversely associated with LS BMD (effect = -0.55; 95% CI, -0.86 to -0.24; P = 0.001), whereas serum selenium levels were positively correlated with HL eBMD (effect = 0.22; 95% CI, 0.10 to 0.33; P = 1.70 × 10-4). Regarding nominal significance, there was a positive association between serum selenium levels and FA BMD. Nominally significant results were also obtained for serum retinol as well as vitamin E levels and HL eBMD. Moreover, sex-specific effects of serum retinol and vitamin E levels on BMD were observed in men. Serum calcium and selenium levels influence BMD at specific skeletal sites. This implies that these nutritional factors play crucial roles in bone metabolism.

Effects of High-Impact Weight-Bearing Exercise on Bone Mineral Density and Bone Metabolism in Middle-Aged Premenopausal Women: A Randomized Controlled Trial

This study examined the effects of high-impact weight-bearing exercise on bone mineral density (BMD) and bone metabolic markers in middle-aged premenopausal women. Forty middle-aged premenopausal women were initially enrolled, but thirty-one participants (40.34 ± 3.69 years) completed in the study. The subjects were randomly divided into two groups including the high-impact weight-bearing exercise group (HWE, n = 14) and control group (CON, n = 17). The HWE group participated in the exercise for 50 min a day, three days per week for four months, while the CON group maintained their regular lifestyle. The HWE program included 10 different high-impact weight-bearing exercises such as jumping and running. BMD was measured using DXA (Hologic, QDR 4500W, Marlborough, MA, USA). The bone metabolic markers including serum 25-(OH) D, intact parathyroid hormone (PTH), osteoprotegerin (OPG), osteopontin (OPN), receptor activator of nuclear factor κB ligand (RANKL), osteocalcin (OC), C-terminal telopeptide of type 1 collagen (CTX), and calcium were analyzed. The results showed that the BMDs of femur, lumbar, and forearm did not significantly change during the intervention period in both the HWE and CON groups. A significant decrease in bone formation markers such as OC (F = 10.514, p = 0.003, ηp2 = 0.266) and an increase in bone resorption marker including CTX (F = 8.768, p = 0.006, ηp2 = 0.232) were found only in the CON group, while these values did not change in the HWE group. There was a significant increase in serum 25-(OH) D (F = 4.451, p = 0.044, ηp2 = 0.133) in the HWE group. Our findings suggest that four months of HWE is not sufficient to improve BMD and bone metabolic markers, but this impact exercise program may prevent the age-associated changes in bone turnover markers in middle-aged premenopausal women.

Estimates of the effects of physical activity on osteoporosis using multivariable Mendelian randomization analysis.

Evidence from epidemiologic studies showed type, frequency, and duration of PA influenced BMD. However, these observational studies may be confounded by many factors, resulting in spurious associations. We aimed to conduct multivariable MR to estimate the causal effect of self-reported and device-measured PA on osteoporosis. Three self-reported and two device-measured PA-related traits were selected as exposures. Outcomes were BMD at different skeletal sites: femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD). Exposure datasets were obtained from UK Biobank with total 377,234 subjects. Outcome datasets were obtained from GEFOS consortium with 53,236 subjects. Standard MR analysis and multivariable MR were conducted to assess the total and direct causal effect of PA on BMD. For self-reported PA, inverse-normalized moderate-to-vigorous had a direct causal effect on FN BMD independently (β = - 1.116 (95% confidence interval, 95%CI: - 2.210, - 0.023), P = 0.045); vigorous PA showed a direct effect (β = 3.592 (95%CI: 0.310, 6.874), P = 0.032) on LS BMD independently. While overall acceleration average and fraction of accelerations both had a direct causal effect on FA BMD independently. Habitual vigorous PA could increase LS BMD. Individuals with higher overall acceleration average would have a higher FA BMD.

Changes in bone mineral density in patients undergoing kidney transplantation

Background and Aims: Bone health in chronic kidney disease (CKD) and its changes after kidney transplantation has been a subject of considerable interest. Kidney transplantation could potentially impact this process positively by reversing hyperparathyroidism, but immunosuppression including steroids could be deleterious to bone health. We studied the baseline and posttransplant bone mineral density (BMD) and factors affecting the changes in BMD after transplantation. Methods: Patients who were included in the study underwent biochemical tests and dual-energy absorptiometry for BMD. These tests were performed at baseline and 8 months after transplantation. Results: The mean BMD in lumbar spine was 1.09 ± 0.15 g/cm2 at baseline and 1.06 ± 0.15 g/cm2 posttransplantation (P = 0.002). The mean BMD at left forearm was 0.88 ± 0.10 g/cm2 at baseline and 0.89 ± 0.10 g/cm2 after transplantation (P = 0.013). The mean BMD at femur was 0.91 ± 0.16 g/cm2 and 0.89 ± 0.10 g/cm2 (P = 0.77) after transplantation. At baseline, intact parathyroid hormone (iPTH) had a significant negative correlation with femoral BMD (r = 0.44, P = 0.02) and 25-hydroxy Vitamin D (25(OH) Vit-D) had a positive correlation with forearm BMD (r = 0.50, P = 0.004). Eight months after transplantation, 25(OH) Vit-D levels showed a positive correlation with lumbar spine BMD (r = 0.36, P = 0.04). Cumulative steroid dose negatively correlated with spine BMD (r = −0.43, P = 0.01) posttransplantation. Conclusions: In this study, the baseline BMD was well preserved. Higher iPTH was associated with lower femoral BMD. Low 25(OH) Vit-D was associated with reduced forearm BMD. There was worsening of spinal BMD and improvement in forearm BMD 8 months after transplantation. No significant change in femoral BMD was noted. Cumulative steroid dose had a significant negative impact on BMD at spine. There were no fractures noted during the study, but two patients had avascular necrosis of the femur.

Shared Genetic Architecture Between Rheumatoid Arthritis and Varying Osteoporotic Phenotypes.

Rheumatoid arthritis (RA) and low bone mineral density (BMD), an indicator of osteoporosis (OP), appear epidemiologically associated. Shared genetic factors may explain this association. This study aimed to investigate the presence of pleiotropy to clarify the potential genetic association between RA and OP. We examined BMDs at varying skeletal sites reported in UK Biobank as well as OP fracture acquired from the Genetic Factors for Osteoporosis (GEFOS) Consortium and the TwinsUK study. PRSice-2 was used to assess the potential shared genetic overlap between RA and OP. The presence of pleiotropy was examined using colocalization analysis. PRSice-2 revealed that RA was significantly associated with OP fracture (β = 351.6 ± 83.9, p value = 2.76E-05), total BMD (β = -1763.5 ± 612.8, p = 4.00E-03), spine BMD (β = -919.8 ± 264.6, p value = 5.09E-04), and forearm BMD (β= -66.09 ± 31.40, p value = 3.53E-02). Through colocalization analysis, the same causal genetic variants, associated with both RA and OP, were apparent in 12 genes: PLCL1, BOLL, AC011997.1, TNFAIP3, RP11-158I9.1, CDK6, CHCHD4P2, RP11-505C13.1, PHF19, TRAF1, C5, and C11orf49 with moderate posterior probabilities (>50%). Pleiotropy is involved in the association between RA and OP phenotypes. These findings contribute to the understanding of disease mechanisms and provide insight into possible therapeutic advancements and enhanced screening measures. © 2021 American Society for Bone and Mineral Research (ASBMR).

Does Baseline PTH Influence Recovery of Bone Mineral Density, Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism

This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery. This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery. Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638±0.093 versus 0.698±0.041 g/cm2; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH. The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline. 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score.

MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk

A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of the Nord-Trøndelag Health Study, followed by imputation in the remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation in MEPE, p.(Lys70IlefsTer26, minor allele frequency [MAF] = 0.8%), was associated with decreased ultradistal forearm BMD (P-value = 2.1 × 10−18), and increased osteoporosis (P-value = 4.2 × 10−5) and fracture risk (P-value = 1.6 × 10−5). The MEPE LoF association with BMD and fractures was further evaluated in 279,435 UK (MAF = 0.05%, heel bone estimated BMD P-value = 1.2 × 10−16, any fracture P-value = 0.05) and 375,984 Icelandic samples (MAF = 0.03%, arm BMD P-value = 0.12, forearm fracture P-value = 0.005). Screening for the MEPE LoF mutations before adulthood could potentially prevent osteoporosis and fractures due to the lifelong effect on BMD observed in the study. A key implication for precision medicine is that high-impact functional variants missing from the publicly available cosmopolitan panels could be clinically more relevant than polygenic risk scores.