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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The role of osteocytes in bone is still an enigma. It was thought that osteocytes are passive cells or ¿¿placeholders¿¿ in bone or, conversely, that osteocytes could potentially be mechanosensors and transducers of mechanical load. A new study [1] now sheds light on the role of osteocytes in maintaining skeletal homeostasis and regulating skeletal responses to mechanical loading. Loading, as occurs with exercise, increases bone mass. Conversely, unloading, as occurs with space flight or immobilization, results in bone loss. The complex lacunocanalicular network connecting all of the osteocytes within bone and cells on the bone surface supports the idea that these cells can sense loading on the skeleton or its absence and then translate those signals to biochemical signals of resorption or formation. The authors used an ingenious approach to determine the role of osteocytes by loss-of-function studies. Using mice carrying a diphtheria toxin (DT) receptor specifically expressed in osteocytes, the authors were able to kill off osteocytes using single injections of DT.

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Oteoblasts develop, synthesize, and deposit extracellular (osteoid) matrix comprising collagen and noncollagenous proteins, and participate in osteoid mineralization. The control of systemic inorganic phosphate (Pi) levels is known to be indispensable for bone formation, especially for osteoid mineralization processes, but the parathyroid hormone (PTH) (decreasing serum Pi levels)-vitamin D (increasing serum Pi levels) axis does not fully explain systemic Pi homeostasis. Attention has been paid to the role of local Pi handling by osteoblasts in bone mineralization. Two related sodium-Pi cotransporters, named Pit1 and Pit2, have been found in osteoblastic cell lines. Molecular inhibition of PiT1 abrogates differentiation and matrix mineralization in osteoblastic cells. In contrast, PiT1 overexpression in smooth muscle cells switches their phenotype from a contractile to an osteogenic one.
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