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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 2

The central role of canonical Wnt signaling in regulating osteoblast lineage specification, expansion, and terminal differentiation.

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The central role of canonical Wnt signaling in regulating osteoblast lin...
Osteoblasts are derived from multipotent mesodermal or neural crest progenitors. Activation of the canonical (ca) Wnt signaling pathway, manifest through β-catenin stabilization, prevents the formation of cartilage (chondrogenesis). Wnt10b prevents adipogenesis (40). The canonical Wnt signaling pathway promotes survival of all cells of the osteoblast lineage and induces the proliferation of preosteoblasts. +, canonical Wnt signaling promotes the process; –, canonical Wnt signaling inhibits the process; AP, alkaline phosphatase; Cola1, collagen α1; DMP1, dentin matrix protein 1; OCN, osteocalcin; Osx, osterix; PTHR, receptor for PTH.

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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