Bone Turnover Markers and Bone Density Across the Menopausal Transition

We measured lunbar spine and femoral neck bone mineral density (BMD); urine markers of bone resorption; serum markers of bone formation; and serum gonadotrophin, estradiol and inhibin concentrations in a population-based cohort of 281 women aged 45-57 yr. Women were classified into pre-, peri-, and postmenopausal groups, depending on menstrual bleeding patterns. Compared with premenopausal women, BMD was lower only in postmenopausal women but not in women currently using hormone replacement therapy (HRT). BMD decreased with age in the perimenopausal group. Compared with premenopausal women, perimenopausal women had 20% greater urine N-telopeptide excretion (P < 0.05) and a doubling of gonadotrophin levels (P < 0.01), whereas serum estradiol and bone formation marker concentrations were no different. Postmenopausal Women had greater levels of bone turnover markers (P < 0.0001), except free deoxypyridinoline and type I procollagen propeptide. Among postmenopausal women, bone resorption markers were lower in those using HRT. Levels of nearly all bone turnover markers were positively related to serum FSH concentrations (P < 0.0001). Overall, the major independent predictors of BMD were age, urine N-telopeptide, serum bone alkaline phosphatase, and serum, FSH, whereas urine free deoxypyridinoline was positively related to BMD in pre- and perimenopausal women. In conclusion, the perimenopause is associated with elevated bone resorption rates and declining BMD, and factors in addition to estrogen deficiency may also contribute to the pathogenesis of postmenopausal osteoporosis.