Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity

Abstract

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/m² and smallest in women with BMI >30 kg/m². 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.

Figure 1.

Mean urine NTX levels (A) and instantaneous rates of change (B) in relation to years from the FMP in the women who experienced a natural FMP (n = 918). The shaded areas denote the 95% confidence intervals.

Figure 2.

Population mean urine NTX, serum estradiol, and serum FSH levels in relation to years from FMP in the women who experienced a natural FMP (n = 918). The dashed lines denote the 95% confidence intervals.

Figure 3.

Mean urine NTX levels and 95% confidence limits (shaded areas) in relation to years from the FMP in women with BMI <25 kg/m² (blue circles and shading), 25–30 kg/m² (red + and shading), or >30 kg/m² (green x and shading).

Figure 4.

Unadjusted (blue solid bars) and adjusted (red hatched bars) mean ± SEM net changes in urine NTX levels across the entire menopause transition in African American, Caucasian, Chinese, or Japanese women. For each woman, the net increase in NTX across the transition was calculated as the difference between the lowest NTX value from any of her visits before the FMP and the highest value from any of her visits after the FMP. Because the values in each woman represent the maximal net change in NTX across the menopause transition, these changes are greater than the difference between the overall mean NTX values before and after the FMP. Unadjusted mean net changes in urine NTX are the average net increases for all women in each of the 4 race/ethnic groups. The adjusted values were generated by restricting the cohort to women with BMI <29 and then adjusting for covariates that differed by ethnicity including study site, BMI, smoking, alcohol intake, physical activity, age at FMP, and the date of the blood draw. a, P < .0001 vs unadjusted values of Japanese women; b, P = .031 vs unadjusted values of Chinese women; c, P < .01 vs unadjusted values of Japanese women; d, P < .01 vs adjusted values of Japanese women.