[Studies on the bone metabolisms in either after natural menopause or surgical menopause: implications of IGF-IGFBP system for postmenopausal osteoporosis].

It is well established that accelerated bone loss occurs in association with estrogen deprivation as seen following the natural menopause and in premenopausal women undergoing surgical oophorectomy (i.e., surgical menopause). We have measured serum levels of bone biochemical markers after both natural menopause and surgical menopause. Circulating levels of insulin-like growth factor-I (IGF-I), which is considered to be the local regulator of osteoblast activity and one of its binding protein, insulin-like growth factor binding protein-4 (IGFBP-4) which binds to IGF-I and suppress its biological activity, were also measured. Bone mineral density measured by dual energy X-ray absorptiometry was decreased more rapidly after surgical menopause. A concomitantly higher rate of bone turnover as assessed by bone biochemical markers was observed after surgical menopause, and thus the levels of procollagen type I C-peptide, pyridinoline and deoxypyridinoline were increased. The serum levels of IGF-I were significantly reduced after natural menopause compared with that after surgical menopause. The levels of IGF-I were correlated with bone mineral density after natural menopause (r = 0.62, p < 0.001), but no significant correlation was observed between these two variables after surgical menopause. The binding activity of IGFBP-4 was significantly greater after surgical menopause than after natural menopause. A stronger inverse correlation existed between the binding activity of IGFBP-4 and bone mineral density after surgical menopause (r = -0.90, p < 0.001) compared to that after natural menopause (r = -0.29, p < 0.05). The simplest explanation is that whereas the loss of bone depends upon the decreased level of IGF-I after natural menopause, after surgical menopause it depends upon the increased level of IGFBP-4.