SHORT-TERM EFFECTS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I ON BONE TURNOVER IN NORMAL WOMEN

Because insulin-like growth factor I (IGF-I) is a potent stimulator of osteoblast proliferation, it has potential in the treatment of osteop orosis. However, IGF-I affects multiple organ systems, and it is uncle ar whether treatment can stimulate bone formation without producing un acceptable side effects. Therefore, we evaluated the effects of treatm ent with recombinant human IGF-I in 18 postmenopausal women who receiv ed various dosages (30, 60, 120, or 180 mu g/kg.day) by sc injections for 6 days. Serum IGF-I concentrations increased by 2- to 4-fold durin g treatment. There were dose-dependent increases in serum type I proco llagen carboxyl-terminal propeptide concentration (r = 0.85, P < 0.001 ), an index of collagen synthesis, and of urinary excretion of deoxypy ridinoline (r = 0.75, P = 0.001), an index of bone collagen breakdown. At the two higher dosages, recombinant human IGF-I caused orthostatic hypotension, sinus tachycardia, bilateral parotid discomfort, weight gain, and edema in some women. Hypoglycemia did not occur. However, tr eatment at the 2 lower dosages increased serum type I procollagen carb oxyl-terminal propeptide significantly and produced minimal or no side effects. Long-term studies on the effects and the safety of low dosag e recombinant human IGF-I on bone mass should now be undertaken in ost eoporotic women.