Effects Of a One-Month Treatment With PTH(1–34) on Bone Formation on Cancellous, Endocortical, and Periosteal Surfaces of the Human Ilium

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Abstract
Using bone histomorphometry, we found that a 1-month treatment with PTH(1-34) [hPTH(1-34)] stimulated new bone formation on cancellous, endocortical, and periosteal bone surfaces. Enhanced bone formation was associated with an increase in osteoblast apoptosis. The precise mechanisms by which hPTH(1-34) increases bone mass and improves bone structure are unclear. Using bone histomorphometry, we studied the early effects of treating postmenopausal women with osteoporosis with hPTH(1-34). Tetracycline-labeled iliac crest bone biopsies were obtained from 27 postmenopausal women with osteoporosis who were treated for 1 month with hPTH(1-34), 50 microg daily subcutaneously. The results were compared with tetracycline-labeled biopsies from a representative control group of 13 postmenopausal women with osteoporosis. The bone formation rate on the cancellous and endocortical surfaces was higher in hPTH(1-34)-treated women than in control women by factors of 4.5 and 5.0, respectively. We also showed a 4-fold increase in bone formation rate on the periosteal surface, suggesting that hPTH(1-34) has the potential to increase bone diameter in humans. On the cancellous and endocortical surfaces, the increased bone formation rate was primarily caused by stimulation of formation in ongoing remodeling units, with a modest amount of increased formation on previously quiescent surfaces. hPTH(1-34)-stimulated bone formation was associated with an increase in osteoblast apoptosis, which may reflect enhanced turnover of the osteoblast population and may contribute to the anabolic action of hPTH(1-34). These findings provide new insight into the cellular basis by which hPTH(1-34) improves cancellous and cortical bone architecture and geometry in patients with osteoporosis.

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