Insulin-like growth factor-I and parathyroid hormone: potential new therapeutic agents for the treatment of osteoporosis

Abstract

Millions of men and women worldwide are afflicted by osteoporosis. As this number is projected to increase over the next half century, attempts to forestall the disease process are being tested. Conventional therapies centre on maintaining bone mineral density (BMD) by blocking bone resorption. However, there is a growing need for drugs that can stimulate new bone formation (anabolic agents), thereby reducing future fracture risk. Both parathyroid hormone (PTH) and insulin like growth factor-I (IGF-I) have been the subject of numerous animal and human studies to determine whether these peptides have promise for the treatment of low bone mass. Although the mechanisms of action for these agents are not well delineated, each protein can activate the osteoblast and thereby enhance bone mass. The effects of these drugs on the osteoclast are less well defined. At the current time, there is considerably more interest in PTH than IGF-I, for several reasons. Firstly, animal studies with PTH are more impressive in terms of histomorphometry and biomechanics than IGF-I; secondly, PTH is specific for the skeleton whereas IGF-I is ubiquitous; and thirdly, human studies with PTH have been relatively devoid of significant side-effects. Large scale Phase III trials are now underway in the US and Europe. It is anticipated that at least one of these peptides may prove to have a role in the prevention and treatment of osteoporosis.