Changes in Bone Resorption Across the Menopause Transition: Effects of Reproductive Hormones, Body Size, and Ethnicity

Objective: Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity. Methods: Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women. Results: Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.5 years after the FMP. NTX levels declined modestly from 2 to 6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began increasing rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI <25 kg/m(2) and smallest in women with BMI >30 kg/m(2). Increases in NTX were greatest in Japanese women and smallest in African Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI. Summary: During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss.