Targeted IGF-I/PDGF for Estrogen Deficiency Osteoporosis

Postmenopausal (estrogen deficiency-induced) osteoporosis is a major public health problempredisposing to fracture and resulting in significant morbidity and mortality. Current therapies canstabilize bone mass but can not repair or restore lost bone. Thus, a critical need exists to improvetherapeutics for the treatment of osteoporosis. Growth factors are essential for bone repair, andexogenous growth factors can augment bone formation. We have demonstrated that the combinationof platelet-derived growth factor (pDGF) and insulin-like growth factor-I (IGF-I) can dramatically stimulatebone repair when applied locally in vivo. However, the systemic administration of growth factors tostimulate generalized bone growth is limited by their equally potent, and less desirable, extra-skeletalactions. This proposal will examine whether IGF-I and PDGF, linked to a bone seeking agent whichtargets them to bone and renders them inactive in the circulation, will prevent bone loss or restore bonemass in estrogen deficient rats. The effects of the growth factors on bone will be followed usingbiochemical markers of bone metabolism, state-of-the-art non-invasive bone densitometry, histomorpho-metry and mechanical strength testing. These studies are designed to lead directly to furtherinvestigations to develop clinically useful therapeutic agents for osteoporosis.