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Normal Growth Hormone Secretory Reserve in Men with Idiopathic Osteoporosis and Reduced Circulating Levels of Insulin-Like Growth Factor-I¹

Departments of Medicine (E.S.K, J.P.B.) and Pharmacology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Queen Elizabeth Hospital (F.K.W.C.), Hong Kong; and St. Joseph Hospital (C.J.R.), Bangor, Maine 04401

Address all correspondence and requests for reprints to: John P. Bilezikian, Department of Medicine, College of Physicians and Sur-geons, 630 West 168th Street, New York, New York 10032.

Many men with idiopathic osteoporosis have reduced circulating insulin-like growth factor-I (IGF-I) levels. The major source of circulating IGF-I is GH-mediated production by the liver. The known anabolic effects of GH on the skeleton raised the possibility of GH deficiency in these men. We sought to test this hypothesis in this study. Fourteen men (mean age, 52.1 ± 3.2 yr, range 31–68) with idiopathic osteoporosis were studied. Mean lumbar spine bone mineral density (BMD) was 0.723 g/cm², T score -3.5; femoral neck BMD was 0.642 g/cm², T score, -3.07; distal (1/3) radius BMD was 0.708 g/cm², T score, -2.05. Eleven of 14 (79%) had frank reductions in serum IGF-I levels compared with age and sex-matched values (158.5 ± 50 SD vs. 180 ± 45 SD). GH secretion was stimulated by iv arginine infusion (30 g) over 30 min followed 1 h later by oral L-dopa (500 mg). Serum GH was measured at time (t) = -15, 0, 30, 45, 60, 90, 120, 150, and 180 min. All patients responded to at least one stimulus with the majority (n = 9) responding to both. Five patients responded either to arginine or to L-dopa but not to both. Baseline GH for the entire group was 0.77 + 0.08 ng/mL (SEM). Peak GH following arginine (t = 45–60 min) was 14.0 ± 2.8 ng/mL, a 17.7 ± 2.8-fold rise. Peak GH following L-dopa (t = 120–180 min) was 5.7 ± 1.0 ng/mL, a 9.2 ± 2.2-fold rise. No difference in maximal secretion was observed between those with low or normal IGF-I levels. Neither IGF-I nor IGF binding protein-3 concentrations changed significantly during the short period of GH stimulation. These data suggest that men with osteoporosis and reduced IGF-I levels do not appear to have a deficiency in the GH axis. Other hormonal or local factors may be important in regulating IGF-I expression. Deficiencies of IGF-I production at skeletal sites may be important in the pathogenesis of this syndrome.

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