Temporal relationship between bone loss and increased bone turnover: a longitudinal study following natural menopause.

We report the results of a longitudinal study aimed at better defining concomitant changes of both bone mineral density (BMD) and of four independent markers of bone turnover (serum osteocalcin, serum alkaline phosphatase activity, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratio) following natural menopause. The results obtained indicate that, within a relatively short period of time since cessation of gonadal function, conventional markers of bone turnover behave differently. In fact, while the mean values of hydroxyproline/creatinine ratio (felt to be a marker of bone resorption) rise immediately at the first control (19.7 +/- 11.7 months), the bone formation markers gradually increase and, as far as serum osteocalcin levels are concerned, this increment appears to be long-lasting. As a result of these changes, a negative skeletal balance follows, which is documented by the prolonged reduction of bone mineral density during the entire observation period. Mean +/- SD % measured yearly bone loss was -2.83 +/- 2.6. There was a highly significant correlation between initial and final BMD values (r = 0.908, p < 0.001; r2 = 82.5) and a weak inverse correlation (r = -0.298, p < 0.046) between initial serum alkaline phosphatase values and % yearly bone loss. In conclusion, measurement of the biological indices of bone remodelling following natural menopause indicate that the increase in osteogenesis is delayed compared to that of bone resorption; furthermore, in the immediate postmenopausal period, the actual bone mass should be considered the best predictor of future bone mass. The inverse correlation found between % yearly bone loss and serum alkaline phosphatase values seems to emphasize the importance of increased bone turnover as an independent predictor of bone loss.