Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
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Granulomas in sarcoidosis express high levels of 1α-hydroxylase, an enzyme that catalyzes the hydroxylation of 25-OH vitamin D to its active form, 1,25(OH)2 vitamin D. Overproduction of 1α-hydroxylase is held responsible for the development of hypercalcemia in sarcoidosis patients. Corticosteroids are used as first-line treatment in organ-threatening sarcoidosis. ⋯ During CAD supplementation, no hypercalcemia developed as a result of supplementation. Hypovitaminosis D seems to be related with more disease activity of sarcoidosis and, therefore, could be a potential risk factor for disease activity of sarcoidosis. Thus, vitamin D-deficient sarcoidosis patients should be supplemented.
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J. Bone Miner. Res. · Nov 2014
Multicenter StudyRisk of Osteoporotic Fractures With Angiotensin II Receptor Blockers Versus Angiotensin-Converting Enzyme Inhibitors in Hypertensive Community-Dwelling Elderly.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are used to treat hypertension; however, in vivo and clinical studies suggest that ARBs and ACE inhibitors may exert different effects on bone. The association between long-term use of ARBs and ACE inhibitors and fracture requiring medical attention is limited. We conducted a population-based, retrospective cohort study with propensity score matching using administrative databases in Ontario, Canada, to examine the risk of osteoporosis-related fractures in hypertensive elderly treated with ARBs versus ACE inhibitors. ⋯ Among new ARB users, 27,815 (96.5%) were successfully matched to ACE inhibitor users. Without dose adjustment, no significant association was observed for ARBs relative to ACE inhibitor users for hip fractures (HR = 0.88; 95% confidence interval [CI] 0.70-1.11), with a decreased risk of other major osteoporotic fractures (HR = 0.81; CI 0.70-0.93) and no significant association for other osteoporotic fractures (HR = 0.88; CI 0.74-1.05). When adjusted for dosage, there was no significant difference between the effects of ARBs and ACE inhibitors on hip (HR = 0.99; CI 0.78-1.25), other major osteoporotic (HR = 0.87; CI 0.75-1.01), and other osteoporotic fractures (HR = 0.90; CI 0.74-1.08).
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J. Bone Miner. Res. · Nov 2014
Influence of aromatase inhibition on the bone-protective effects of testosterone.
The influence of the aromatase enzyme in androgen-induced bone maintenance after skeletal maturity remains somewhat unclear. Our purpose was to determine whether aromatase activity is essential to androgen-induced bone maintenance. Ten-month-old male Fisher 344 rats (n = 73) were randomly assigned to receive Sham surgery, orchiectomy (ORX), ORX + anastrozole (AN; aromatase inhibitor), ORX + testosterone-enanthate (TE, 7.0 mg/wk), ORX + TE + AN, ORX + trenbolone-enanthate (TREN; nonaromatizable, nonestrogenic testosterone analogue; 1.0 mg/wk), or ORX + TREN + AN. ⋯ In contrast, TE and TREN produced potent myotrophic effects in the LABC muscle and maintained fat mass at the level of Shams. AN co-administration did not alter androgen-induced effects on muscle or fat. In conclusion, androgens are able to induce direct effects on musculoskeletal and adipose tissue, independent of aromatase activity.
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J. Bone Miner. Res. · Sep 2014
Fracture risk predictions based on statistical shape and density modeling of the proximal femur.
Increased risk of skeletal fractures due to bone mass loss is a major public health problem resulting in significant morbidity and mortality, particularly in the case of hip fractures. Current clinical methods based on two-dimensional measures of bone mineral density (areal BMD or aBMD) are often unable to identify individuals at risk of fracture. We investigated predictions of fracture risk based on statistical shape and density modeling (SSDM) methods using a case-cohort sample of individuals from the Osteoporotic Fractures in Men (MrOS) study. ⋯ The SSDM-based prediction model adjusted by age correctly identified 55% of the fracture cases (and 94.7% of the non-cases), whereas the clinical standard aBMD correctly identified 10% of the fracture cases (and 91.3% of the non-cases). SSDM identifies subtle changes in combinations of structural bone traits (eg, geometric and BMD distribution traits) that appear to indicate fracture risk. Investigation of important structural differences in the proximal femur between fracture and no-fracture cases may lead to improved prediction of those at risk for future hip fracture.
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J. Bone Miner. Res. · Aug 2014
A novel osteogenic oxysterol compound for therapeutic development to promote bone growth: activation of hedgehog signaling and osteogenesis through smoothened binding.
Osteogenic factors are often used in orthopedics to promote bone growth, improve fracture healing, and induce spine fusion. Osteogenic oxysterols are naturally occurring molecules that were shown to induce osteogenic differentiation in vitro and promote spine fusion in vivo. The purpose of this study was to identify an osteogenic oxysterol more suitable for clinical development than those previously reported, and evaluate its ability to promote osteogenesis in vitro and spine fusion in rats in vivo. ⋯ Unlike rhBMP-2, Oxy133 did not induce adipogenesis in the fusion mass and resulted in denser bone evidenced by greater bone volume/tissue volume (BV/TV) ratio and smaller trabecular separation. Findings here suggest that Oxy133 has significant potential as an osteogenic molecule with greater ease of synthesis and improved time to fusion compared to previously studied oxysterols. Small molecule osteogenic oxysterols may serve as the next generation of bone anabolic agents for therapeutic development.