The role of prostaglandins in the regulation of bone metabolism.

Prostaglandins are likely to play an important role in the physiologic and pathologic responses of skeletal tissue. They are potent agonists that can stimulate and inhibit bone resorption and formation. In vivo, the major effect of exogenous prostaglandins, particularly prostaglandin E2, is to stimulate resorption and formation. These effects appear to involve replication and differentiation of osteoclast and osteoblast precursors, and to be mediated at least in part by cyclic 3' 5' adenosine monophosphate. Prostaglandins can inhibit the activity of isolated osteoclasts, probably also by a cyclic 3' 5' adenosine monophosphate-mediated mechanism. Inhibition of collagen synthesis can be seen in cell and organ cultures and appears to be caused by a receptor selective for prostaglandins of the F series and to involve activation of protein kinase C. Prostaglandin production by bone cells is regulated highly by mechanical forces, cytokines, growth factors, and systemic hormones. Prostaglandins also can amplify their own production. Regulation is associated with marked changes in the newly described "inducible" prostaglandin G/H synthase with less effect on the constitutive enzyme. Prostaglandins also may play a role in postmenopausal bone loss because estrogen deficiency, which increases bone turnover, can increase prostaglandin production in bone.