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Insulin-Like Growth Factor-I in Men with Idiopathic Osteoporosis¹

Departments of Medicine (E.S.K., F.C., E.S., R.L., J.P.B.), Pathology (D.D.), and Pharmacology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, N.Y. 10032; St. Joseph Hospital (C.J.R.), Bangor Maine; Regional Bone Center (F.C., R.L., D.D.), Helen Hayes Hospital, West Haverstraw, New York; Irving Center for Clinical Research (D.M.), Columbia-Presbyterian Medical Center, New York, N.Y. 10032; Queen Elizabeth Hospital (F.C.), Hong Kong

Address correspondence and requests for reprints to: John P. Bilezikian, M.D., Department of Medicine, College of Physicians and Surgeons, 630 W. 168th Street, New York, N.Y. 10032.

The etiology of osteoporosis in most men without a history of alcohol abuse, hypogonadism, or glucocorticoid excess is unknown. Several histomorphometric reports have demonstrated a reduction in indices of bone formation. We tested the hypothesis that the putative reduction in bone formation in men with idiopathic osteoporosis may be related to deficiencies in skeletal mechanisms that are mediated by insulin-like growth factor I (IGF-I). Twenty-four middle-aged men (50.5 ± 1.9 yr) with severe idiopathic osteoporosis (mean lumbar spine T-score -3.5 ± 0.16) were studied. The following biochemical indices were all normal: serum calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, testosterone, osteocalcin, carboxyterminal propeptide of type I collagen, bone specific alkaline phosphatase, urinary calcium, and collagen crosslinks. Parathyroid hormone level was in the lower range of normal, 25 ± 2 pg/mL (nl: 10–65). Mean serum IGF-I level was also in the lower range of normal, 157.9 ± 7.6 ng/mL (normal age-matched range, 140–260 ng/mL). Eight men had IGF-I levels that were below 140 ng/mL. The mean IGF-I Z score was -0.75, significantly different from the expected mean of zero (P = 0.0002). IGF-I was correlated negatively with age (r = -0.49, P < 0.02). With age held constant, serum IGF-I accounted for 15% of the variance in lumbar bone mineral density (BMD; P < 0.001). The osteocalcin concentration correlated well with bone density at the distal 1/3 radius (r = + 0.44; P < 0.002).

Histomorphometric analysis of bone biopsy specimens showed significant reductions in cancellous bone volume (31%; P < 0.001), cortical width (28%; P < 0.05), osteoid surface (33%; P < 0.01), and bone formation rate (54%; P < 0.01) when results were compared with age-matched control subjects. Percent eroded surface was normal and was correlated inversely with serum IGF-I levels (r = -0.5; P < 0.04).

These results suggest that serum IGF-I levels are reduced in men with idiopathic osteoporosis and that IGF-I correlates with and may contribute to the reduction in lumbar spine bone mass density (BMD). The low IGF-I levels may reflect the reduction in bone formation demonstrated by histomorphometry. Insights into the etiology of idiopathic osteoporosis in men may be revealed by further studies of the IGF-I axis.

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