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Building bone to reverse osteoporosis and repair fractures
Sundeep Khosla, … , Jennifer J. Westendorf, Merry Jo Oursler
Sundeep Khosla, … , Jennifer J. Westendorf, Merry Jo Oursler
Published February 1, 2008
Citation Information: J Clin Invest. 2008;118(2):421-428. https://doi.org/10.1172/JCI33612.
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Building bone to reverse osteoporosis and repair fractures

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Abstract

An important, unfilled clinical need is the development of new approaches to improve fracture healing and to treat osteoporosis by increasing bone mass. Recombinant forms of bone morphogenetic protein 2 (BMP2) and BMP7 are FDA approved to promote spinal fusion and fracture healing, respectively, and the first FDA-approved anabolic drug for osteoporosis, parathyroid hormone, increases bone mass when administered intermittently but can only be given to patients in the US for two years. As we discuss here, the tremendous explosion over the last two decades in our fundamental understanding of the mechanisms of bone remodeling has led to the prospect of mechanism-based anabolic therapies for bone disorders.

Authors

Sundeep Khosla, Jennifer J. Westendorf, Merry Jo Oursler

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Figure 4

Potential cellular targets for the anabolic effects of PTH.

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Potential cellular targets for the anabolic effects of PTH.
PTH targets ...
PTH targets multiple cell types to mediate its bone anabolic effects. Specifically, PTH decreases apoptosis and proliferation of osteoblasts (OBs), as well as increasing their differentiation. It can activate bone-lining cells into functioning osteoblasts and decrease sclerostin production by osteocytes, which would be expected to increase Wnt signaling to osteoblasts. Finally, PTH is postulated to stimulate factors produced by osteoclasts (OCs) that stimulate osteoblasts.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 4 patents
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