Bone loss in premenopausal, perimenopausal and postmenopausal women: results of a prospective observational study over 9 years.

INTRODUCTION: Few longitudinal data about rates of bone loss in women in midlife exist. Fewer still with their reproductive states having been carefully assessed and sequentially followed-up.
METHODS: Complete data from 50 women younger than 60 years (mean age at baseline 48.3 ± 5.4 years) were prospectively collected over 9 years. This was done by standardized interviews, measurement of endocrinological parameters as well as bone markers and repeated bone mineral density (BMD) measurements using quantitative computer tomography (QCT). Women were classified in three groups according to their reproductive characteristics over 9 years.
RESULTS: Significant BMD loss was found in women going through the menopausal transition. In perimenopause, there was a correlation (multiple regression results, r = -0.396 and r = -0.527) between accelerated bone density loss and increased gonadotropin levels (follicle stimulating hormone, luteinizing hormone). Although significantly higher levels of bone markers (osteocalcin, bone-specific alkaline phosphatase, c-terminal telopeptide cross-linked collagen type I) were measured in postmenopause, the greatest increase in these markers was seen during the menopausal transition. No individual marker's increase, however, was predictive for perimenopausal bone density loss. The major risk factors for rapid bone loss were a lower initial body weight (< 57 kg), a body mass index < 20 kg/m(2) as well as a positive family history of fragility fractures.
CONCLUSIONS: Women in the menopausal transition lose trabecular bone at a rapid rate despite intermittently high and usually normal estrogen levels. This is the only prospective study to date that documents trabecular bone changes in women through the entire perimenopause, which may last up to 10 years.