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Division of Endocrinology (M.J.H., M.B.T., A.G.-O., A.F.S.), The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; and Department of Orthopedics (C.G.), Yale University School of Medicine, New Haven, Connecticut 06520
Address all correspondence and requests for reprints to: Andrew F. Stewart, M.D., Division of Endocrinology, BST E-1140, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, Pennsylvania 15213. E-mail: stewart{at}msx.dept-med.pitt.edu.
PTH-related protein (PTHrP) is homologous with PTH. PTH, an effective anabolic agent for treating osteoporosis, has been shown to stimulate both bone resorption by osteoclasts and bone formation by osteoblasts. We examined whether PTHrP might share anabolic properties in osteoporosis. A 3-month double-blind, prospective, placebo-controlled, randomized clinical trial was performed in 16 healthy postmenopausal women with osteoporosis. All received calcium and vitamin D, and all continued their prior hormone replacement therapy. One group also received daily sc PTHrP (6.56 µg/kg·d, or approximately 400 µg/d), and the other group received placebo injections.
The PTHrP group displayed a 4.7% increase in lumbar spine bone mineral density (BMD) and also demonstrated an increase in osteoblastic bone formation, as assessed using serum osteocalcin measurements. In contrast, there was no increase in bone-specific alkaline phosphatase and collagen-1 propeptide or either of two markers of osteoclastic bone resorption, N-telopeptide, or deoxypyridinoline. One subject in the placebo group withdrew from the study, but there were no significant adverse events in the PTHrP group.
PTHrP administered sc in high doses for only 3 months appears to be a potent anabolic agent, producing a 4.7% increase in lumbar spine BMD. This compares very favorably to available antiresorptive drugs for osteoporosis and is similar to the increases in BMD at this early time point reported for PTH. Despite the high doses, PTHrP was well tolerated. Larger clinical trials are required to confirm these results and fully assess the anabolic potential of PTHrP in osteoporosis.
This work was supported by NIH Grants DK 55081 and AR 38460.
Abbreviations: BMD, Bone mineral density; DPD, deoxypyridinoline; NS, not significant; NTX, N-telopeptide; P1CP, collagen-1 propeptide; PTHrP, PTH-related protein.
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