INSULIN-LIKE GROWTH-FACTOR-I IN MEN WITH IDIOPATHIC OSTEOPOROSIS

The etiology of osteoporosis in most men without a history of alcohol abuse, hypogonadism, or glucocorticoid excess is unknown. Several hist omorphometric reports have demonstrated a reduction in indices of bone formation. We tested the hypothesis that the putative reduction in bo ne formation in men with idiopathic osteoporosis may be related to def iciencies in skeletal mechanisms that are mediated by insulin-like gro wth factor I(IGF-I). Twenty-four middle-aged men (50.5 +/- 1.9 yr) wit h 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, testoster one, osteocalcin, carboxyterminal propeptide of type I collagen, bone specific alkaline phosphatase, urinary calcium, and collagen crosslink s. 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 rang e 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 I GF-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 dis tal 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 surf ace (33%; P < 0.01), and bone formation rate (54%; P < 0.01) when resu lts were compared with age-matched control subjects. Percent eroded su rface 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 ar e reduced in men with idiopathic osteoporosis and that IGF-I correlate s with and may contribute to the reduction in lumbar spine bone mass d ensity (BMD). The low IGF-I levels may reflect the reduction in bone f ormation demonstrated by histomorphometry. Insights into the etiology of idiopathic osteoporosis in men may be revealed by further studies o f the IGF-I axis.