Bone
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Elevated extracellular calcium (Ca(e)) stimulates both chemotaxis and mitogenesis of MC3T3-E1 osteoblasts via a calcium-sensing receptor (CasR). Ca(e)-mediated chemotaxis of these bone-forming cells is dependent on phospholipase C (PLC) and blocked by the Gi-protein inhibitor pertussis toxin. In this study, we examine the signaling mechanisms by which the CasR stimulates PLC activity in MC3T3-E1 osteoblasts. ⋯ Inhibition of protein kinase C (PKC) disrupted Ca(e)-stimulated tyrosine phosphorylation of PLC-gamma1. In addition, exposure to pertussis toxin or exogenous activation of protein kinase A (PKA) inhibited PLC-gamma1 tyrosine phosphorylation in response to Ca(e). The results indicate that: (a) the osteoblast CasR activates PLC-gamma1 downstream of PLC-beta in a PKC-dependent manner; (b) PKA is a negative regulator of Ca(e)-promoted PLC-gamma1 phosphorylation; and (c) Gq and Gi are both involved in the CasR-mediated phosphorylation of PLC-gamma1.
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Comparative Study
Static histomorphometry of human iliac crest and vertebral trabecular bone: a comparative study.
We recently developed a new, rapid method for conducting static histomorphometry on large histologic sections. This method has now been applied on both iliac crest and lumbar vertebral bone to compare the age-related changes at these two skeletal sites and to investigate the correlation between the histomorphometric measures at the iliac crest and the vertebral body. The material comprised matched sets of unilateral transiliac crest bone biopsies and lumbar vertebral bodies (L-2) from 24 women (19-96 years) and 24 men (23-95 years) selected from a larger autopsy material. ⋯ Trabecular bone volume showed a correlation coefficient of r = 0.59. It is concluded that static histomorphometry performed on one skeletal site does not automatically predict static histomorphometric measures at another skeletal site. Therefore, it is recommended that static histomorphometry be performed at the skeletal site of interest-if at all possible.
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Records from the General Practice Research Database were used to derive age- and gender-specific fracture incidence rates for England and Wales during the period 1988-1998. In total, 103,052 men and 119,317 women in the sample of 5 million adults sustained a fracture over 10.4 million and 11.2 million person-years (py) of follow-up. Among women, the most frequent fracture sites were the radius/ulna (30.2 cases per 10,000 py) and femur/hip (17.0 per 10,000 py). ⋯ The lifetime risk of any fracture was 53.2% at age 50 years among women, and 20.7% at the same age among men. Whereas fractures of the proximal femur and vertebral body were associated with excess mortality over a 5 year period following fracture diagnosis among both men and women, fractures of the distal forearm were associated with only slight excess mortality in men. This study provides robust estimates of fracture incidence that will assist health-care planning and delivery.
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We assessed the current trends in the number and incidence of osteoporotic knee fractures in Finland by collecting data from the National Hospital Discharge Register for all patients > or =60 years of age who were admitted to Finnish hospitals in 1970-1999 for primary treatment of such fractures. The knee fracture was defined "osteoporotic" if it was caused by a low-energy trauma only; that is, a fall from standing height or less. We also predicted fracture development until the year 2030 by a regression model, which took into account the predicted changes in the fracture incidences and population at risk. ⋯ If this trend continues, there will be about 2.5 times more osteoporotic knee fractures in Finnish women in the year 2030 than there were in 1999. In Finnish men aged > or =60 years, the annual number of fractures and its changes were clearly smaller (77 in 1970 vs. 138 in 1999), and the fracture incidence did not show consistent trend changes over time (30 in 1970 vs. 34 in 1999). We conclude that in elderly Finnish women the number of osteoporotic knee fractures shows a rise with a rate that cannot be explained merely by demographic changes and, therefore, vigorous preventive measures are needed to control this development.
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This study compares effects of maintenance doses of human parathyroid hormone [hPTH(1-84)], 17beta-estradiol (E2), and risedronate on distal femur bone mineral density and proximal tibia cancellous bone histomorphometry in ovariectomized (ovx), osteopenic rats previously administered a higher dose of hPTH. Nine groups (n = 8) of 3.5-month-old ovx or intact Sprague-Dawley rats were left untreated for 11 weeks to allow for the development of cancellous osteopenia in the ovx groups. Next, the ovx rats received subcutaneous injections of hPTH (75 microg/kg per day, three times per week) or vehicle for 12 weeks. ⋯ Thus, in osteopenic rats, the increment in distal femur BMD and proximal tibia BV/TV gained by 12 weeks of hPTH treatment was lost within 24 and 12 weeks of treatment termination, respectively. Low-dose hPTH maintained BMD and BV/TV after hPTH treatment by stimulating bone formation, whereas risedronate maintained BMD and BV/TV by reducing bone resorption. E2 in a maintenance dose failed to maintain BMD and BV/TV after withdrawal of hPTH treatment.