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Because insulin-like growth factor I (IGF-I) is a potent stimulator of osteoblast proliferation, it has potential in the treatment of osteoporosis. However, IGF-I affects multiple organ systems, and it is unclear whether treatment can stimulate bone formation without producing unacceptable side effects. Therefore, we evaluated the effects of treatment with recombinant human IGF-I in 18 postmenopausal women who received various dosages (30, 60, 120, or 180 micrograms/kg.day) by sc injections for 6 days. Serum IGF-I concentrations increased by 2- to 4-fold during treatment. There were dose-dependent increases in serum type I procollagen carboxyl-terminal propeptide concentration (r = 0.85, P < 0.001), an index of collagen synthesis, and of urinary excretion of deoxypyridinoline (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, treatment at the 2 lower dosages increased serum type I procollagen carboxyl-terminal propeptide significantly and produced minimal or no side effects. Long-term studies on the effects and the safety of low dosage recombinant human IGF-I on bone mass should now be undertaken in osteoporotic women.

A B S T R A C T The effect of sex hormones on bone tissue was studied in 12 osteoporotic patients. Surfaces of bone undergoing formation and resorption were determined by quantitative microradiography of iliac crest biopsy samples before and after treatment with estrogens in 11 postmenopausal women and with testosterone in one gonadally competent man. Before treatment, bone resorption was greater than normal in all but one patient and bone formation was normal. After treatment, bone resorption decreased to within the normal range in all patients, and bone formation did not change significantly. Biochemical studies showed significant decreases in serum calcium, phosphorus, and alkaline phosphatase levels and in urinary excretion of calcium and hydroxyproline. These changes are believed to be the consequence of the effect of the hormones on bone. The data indicate that the major effect of sex hormones in osteoporosis is an inhibition of bone resorption. INTRODUCTIONAlbright, Smith, and Richardson in 1941 proposed that anabolic sex hormones were necessary for bone matrix synthesis, and that the loss of estrogens at the menopause in women or of androgens with aging in men caused osteoporosis (1). Since then, sex hormones have been used extensively in the treatment of osteoporosis, although their mechanism of action and therapeutic usefulness have not been completely established.Estrogens stimulate intramedullary bone formation in birds (2), but their effect on mammalian bone is variable. Experiments have demonstrated increased endosteal formation in mice (3), decreased endosteal resorption in rats (4), and no specific skeletal response in