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The Roles of Small GTPases in Osteoclast Biology

Megan M. Weivoda and Merry Jo Oursler

The adult skeleton undergoes bone remodeling that consists of bone formation by osteoblasts and bone resorption by osteoclasts. When the amount of bone resorbed is greater than the amount of new bone formed, low bone mass results, putting individuals at increased risk for osteoporosis and osteoporotic bone fracture. Nitrogenous bisphosphonates (NBPs) are the most common first line treatment for conditions of low bone mass. NBPs reduce osteoclast bone resorption by impairing the post-translational modification of small GTPases. Small GTPases play crucial roles in the differentiation, function, and survival of osteoclasts. Understanding the roles of individual small GTPases in osteoclast biology may lead to more targeted therapies for the treatment of low bone mass. In this review, we discuss recent investigations into the in vivo effects of individual GTPase deletion in osteoclasts and the molecular roles for small GTPases in osteoclast biology.