Bone adjusts its structure to become better suited to withstand the mechanical demands it experiences. Physical loading and routine activities have been shown to inhibit bone resorption. However, the cellular mechanism underlying this phenomenon remains largely unknown. The focus of a recent study [1] was to determine the mechanisms by which osteocytes might transduce and regulate bone resorption, and the antiresorptive effects of loading.
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Despite the sexual dimorphism of bone, hip fracture risk is very similar in men and women at the same absolute bone mineral density (BMD). A recent study was conducted with the objective of elucidating the main structural properties of bone that underlie the measured BMD and that ultimately determine the risk of hip fracture in elderly men and women [1]. This study is part of the Rotterdam Study (a large prospective population-based cohort) and included 147 incident hip fracture cases in 4806 participants with DXA-derived hip structural analysis (mean follow-up, 8.6 y).
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Calcineurin is a protein phosphatase that regulates several physiological processes and is the target for cyclosporine A. Pharmacological inhibition of calcineurin by low concentrations of cyclosporin A increases osteoblast differentiation in vitro and bone mass in vivo. To determine whether calcineurin exerts direct actions on osteoblasts, the authors of a recent study [1] generated mice lacking a calcineurin regulatory subunit selectively in osteoblasts.
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Cardiovascular disease and osteoporotic fractures are two major public health problems. Cardiovascular disease and osteoporosis coexist in women: progression of aortic calcifications has been associated with faster bone loss. Low BMD has been shown to predict cardiovascular events and cardiovascular mortality, whereas the association between the extension of aortic calcifications and hip fracture risk is controversial. In contrast to these findings in women, few studies concern the relationship between osteoporosis and cardiovascular disease in men.
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Some studies have reported associations between cardiovascular diseases (CVD) and bone mineral loss. Osteoclast regulatory factors can affect vascular calcifications, and a high blood pressure can induce abnormalities in calcium metabolism and increase bone mineral loss in women. Low bone mineral density is not only an important predictor of osteoporotic fracture, but is also a risk factor for mortality.
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Osteoporosis is a progressive and debilitating disease that is characterized by massive bone loss during the first 10 years following the menopause, with a deterioration of bone tissues, and propensity for fragility fractures. Until recently, the major drugs to treat osteoporosis were inhibitors of bone remodeling reducing both bone resorption and formation, or anabolic drugs, increasing bone remodeling by enhancing bone formation, but also increasing bone resorption. Strontrium ranelate is the first antiosteoporotic treatment that has dual mode of action and simultaneously increases bone formation, while decreasing bone resorption, thus rebalancing bone turnover of favor of bone formation.
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The differentiation of multipotent stemcells of mesodermal origin results in the formation of adipocytes, chondrocytes, osteoblasts, and myoblasts. In humans, osteoporosis and age-related osteopenia are associated with an increase in marrow fat tissue and osteoblast numbers correlated negatively with the number of adipocytes. Osteoblastic differentiation is driven by runx2, and then characterized by the expression of alkaline phosphatase, osteocalcin, and eventually by the mineralization of the extracellular matrix.
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Skeletal development and turnover occur in close spatial and temporal association with angiogenesis. Osteoblasts are ideally situated in bone to sense oxygen tension and respond to hypoxia by activating the hypoxia inducible factor α (HIFα) pathway. An elegant study [1] provides evidence that HIFα promotes angiogenesis and osteogenesis by elevating vascular endothelial growth factor (VEGF) levels in osteoblasts. Mice overexpressing HIFα in osteoblasts through selective deletion of the von Hippel¿Lindau gene (Vhl), a factor which usually promotes degradation of HIFα , expressed high levels of Vegf and developed extremely dense, heavily vascularized long bones.
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