The cost of osteoporosis is immense, both financially and medically. There is a 20% mortality rate from hip fractures, and spinal fractures are associated with major changes in quality of life. this disease affects nearly 20 million Americans and is increasing in prevalence, in part because men and women are living longer, and in part because of better diagnostic methods to detect low bone density via dual energy xray absorptiometry before fractures occur. However, the pathophysiology of osteoporosis is poorly understood, and treatment options are limited to slowing bone loss rather than to augmenting bone mass. In spite of evidence that anti-resorptive agents ~ estrogen, calcitonin, and bisphosphonates ~ can prevent additional bone loss and reduce fractures, there is a tremendous clinical need for new therapeutic agents that can increase bone density by stimulating bone formation. One such potential anabolic agent is parathyroid hormone (PTH). One possible mechanism for PTH action on bone involve growth hormone (GH) ad insulin-like growth factor-I (IGF-I), important stimulatory agents for bone formation. Unfortunately, often patients who present with low bone density are also deficient for these bone growth factors. In this application we present a murine model of GH./IGF-I deficiency accompanied by low bone density, a condition analogous to these GH/IGF-I deficient elders. This model represents an ideal system within which to test the therapeutic potential of PTH as an anabolic therapy for GH/IGF-I deficiency-induced bone density and to determine its mechanism of action.
NIH ExPorter
NIH ExPorter