The pathophysiology of peri- and postmenopausal bone loss

Changes in sex hormones and bone turnover were studied longitudinally in 31 women aged 47-54 years who were approaching the menopause. Every 6 weeks for 2-3 years, hormones and biochemical estimates of the bone turnover were determined and the bone mass was measured at two forearm sites by single photon absorptiometry. Spinal bone mass was measured every 6 months. The bone turnover was normal in women aged 47-54 years with regular menstruation, whereas the estimates of bone resorption were high in the women with irregular menstruation. In nine women, who reached the menopause during the study, bone resorption increased significantly, whereas bone formation showed only a small increase. When the results of the nine women were combined with those of 50 women, who had passed a natural menopause within the preceding 3.5 years, the bone resorption indices reached their peak within the first postmenopausal year, whereas bone formation increased until 1.5-2 years after the last menstrual cycle. At the ultradistal forearm site the rate of bone loss was maximal (5% per year) immediately after the menopause and subsequently declined, which suggests that trabecular bone is more sensitive than cortical bone to changes in bone turnover. Spinal bone loss was identical in late peri- and early postmenopausal women. We conclude that bone resorption starts to increase during the last perimenopausal years, with a beginning acceleration in bone loss, which then becomes sharp after the menopause. The changes are related to the decline in oestrogens, but other mechanisms may also play a role.