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Gade Fitzpatrick posted an update 6 months, 3 weeks ago
rength before changes in DXA occur and may result from poor diabetic control. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.This study investigates the sex steroid hormone profile in younger men with distal radius fracture (DRF) to elucidate if this could explain the low bone density and osteoporosis previously observed. In a case-control study, 73 men with DRF (mean age 38 ± 9 years; range, 20-51) was compared with 194 age-matched, population controls. Performed assays total testosterone (TT), calculated free testosterone (cFT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and total estradiol (E2). BMD hip and spine were measured. Fracture cases had lower cFT (298 versus 329 pmol/L; p = 0.008), but not TT, compared with controls. FSH and SHBG were not statistically different. LH was almost 30% higher (5.7 versus 4.5 IU/L; p less then 0.001) and a lower E2 was observed (80.0 versus 87.1; p = 0.098). Men with DRF had a lower E2/SHBG ratio compared with controls (2.3 versus 2.9; p = 0.013). A higher proportion of the fracture group had low TT ( less then 10.5 nmol/L; 21% versus 11%; p = 0.052), low cFT ( less then 220 pmol/L; 18% versus 8%; p = 0.017), and low E2 ( less then 73 pmol/L; 48% versus 35%; p = 0.044). Odds ratio (OR) for fracture when having low cFT was 2.3 (95% CI, 1.02-5.49; p = 0.044); with low E2, the OR was 1.7 (95% CI, 0.96-2.96). In this study in young men with DRF exploring sex hormone levels, we find that sex hormone profiles may be disturbed with a lower E2/SHBG ratio, lower cFT, and higher LH. Estrogen is also a strong determinant of bone mass in men; hence, low levels of E2 may be contributing to the observed lower BMD and these differences may be relevant to fracture risk. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.Vitamin D deficiency is reported in individuals with primary hyperparathyroidism (PHP). However, decreased 25OHD may be attributed to enhanced conversion into 1,25-hydroxyvitamin D . To examine vitamin D metabolism in individuals with PHP, serum calcium, PTH, 25OHD, and 1,25(OH)D levels were determined in 210 adults 102 with PHP, 40 with normal 25OHD, and 68 with vitamin D deficiency. Concentrations were redetermined in 37 individuals with PHP following vitamin D supplementation and 43 patients postsurgery. Comparisons were conducted by Student’s t test and ANOVA. Correlations were assessed between PTH and 25OHD, 1,25(OH)D, and 1,25(OH)D/25OHD in individuals with PHP. Calcium, PTH, and 1,25(OH)D were higher (p less then 0.001) in individuals with PHP (11.4 ± 0.4, 116 ± 21, 79 ± 6) than in individuals with normal 25OHD (9.6 ± 0.2, 49 ± 5, 57 ± 6) and vitamin D deficiency (9.3 ± 0.2, 62 ± 6, 32 ± 4). Compared with individuals with normal 25OHD (47 ± 5), 25OHD was lower (18 ± 3), but not different from subjects with vitamin D deficiency (15 ± 2). In individuals with PHP, vitamin D2 supplementation induced rises in 1,25(OH)D and calcium without lowering PTH, whereas postsurgery, calcium, PTH, 25OHD, and 1,25(OH)D normalized. Finally, in individuals with PHP, significant correlations (p less then 0.01) were documented between PTH and calcium (r = 0.74), 25OHD (r = -0.43), 1,25(OH)D (r = 0.52), and 1,25(OH)D/25OHD (r = 0.46); and between 1,25(OH)D/25OHD and calcium (r = 0.47). Subnormal 25OHD in most individuals with PHP may be attributed to enhanced conversion to 1,25(OH)D-not “true” vitamin D deficiency-although in some patients, both PHP and vitamin D deficiency coexisted. Moreover, vitamin D supplementation exaggerated hypercalcemia in individuals with PHP. © 2020 The Author. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.In endochondral ossification, chondroblasts become embedded in their matrix and become chondrocytes, which are mature cells that continue to proliferate, eventually becoming hypertrophic. Hypertrophic chondrocytes produce cartilage that is then resorbed by osteoclasts prior to bone matrix replacement via osteoblasts. Although sexually dimorphic bone phenotypes have long been characterized, specific modulation of the growth plate during a critical window in sexual maturation has not been evaluated. Here we report that specific depletion of osteocalcin- (OCN-) expressing cells in vivo during sexual maturation leads to dimorphic bone phenotypes in males and females. At 6 to 8 weeks of age, OCN-Cre;iDTR (inducible diphtheria toxin receptor-expressing) mice were treated with diphtheria toxin (DT) for 2 weeks to deplete OCN+ cells. At the end of the study, long bones were collected for μCT and histomorphometry, and serum was collected for proteomic and lipidomic analyses. Ablation of OCN+ cells in mice leads to consistent trends for weight loss after 2 weeks of treatment. Females exhibited decreased skeletal parameters in response to OCN+ cell ablation treatment, as expected. However, OCN+ cell ablation in males uniquely displayed an expansion of hypertrophic chondrocytes, a widening of the growth plate, and an abnormal “clubbing” anatomy of the distal femur. Following DT treatment, mice from both sexes also underwent metabolic cage analysis, in which both sexes exhibited decreased energy expenditure. Smad phosphorylation We conclude that skewing endochondral bone formation during longitudinal growth has a profound effect on body weight and energy expenditure with sex-specific effects on developing bone. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.Zoledronic acid is a bisphosphonate commonly used to treat bone diseases such as osteoporosis and cancer-induced bone disease. Patients exhibit a variable sensitivity to zoledronic acid; the underlying explanation for this remains unclear. The objective of this study was to obtain more knowledge in this regard. We hypothesized that osteoclasts generated from different individuals would show a variable sensitivity to zoledronic acid in vitro. Osteoclasts were generated using monocytes from 46 healthy female blood donors (40 to 66 years). Matured osteoclasts were reseeded onto bone slices precoated with different concentrations of zoledronic acid. IC50 values were determined based on total eroded bone surface after 3 days of resorption. The IC50 for inhibition of osteoclastic bone resorption varied from 0.06 to 12.57μM zoledronic acid; thus, a more than 200-fold difference in sensitivity to zoledronic acid among osteoclasts from different individuals was observed. Multiple linear regression analyses showed that the determined IC50 correlated with smoking status, and the average number of nuclei per osteoclast in vitro.