In postmenopausal women, faster increases in bone turnover during the menopausal transition and greater bone turnover in the early postmenopausal period are associated with an increased risk for fracture, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

The study included women who were premenopausal or early perimenopausal at baseline of the Study of Women’s Health Across the Nation (SWAN) who transitioned to postmenopause during the study period. Menopausal transition was defined as 2 years before to 2 years after the final menstrual period. Early postmenopause was defined as ≥2 years after the final menstrual period.

Patients were included if they had available data on the date of their final menstrual period, urinary levels of the bone turnover marker collagen type 1 N-telopeptide (NTX), bone mineral density (BMD), and incident fracture. The researchers used Cox proportional hazards regression to estimate whether the rate of increase in urinary NTX across the menopausal transition predicted time to first fracture, controlling for several factors.

The mean urine NTX was 36.8±17.5 nM BCE/nM Cr at the start of the menopausal transition and 48.8±22.5 nM BCE/nM Cr in early postmenopause. After the early postmenopausal visit, 65 incident fractures occurred in all patients, of which 58.5% (n=38) were categorized as minimum trauma. The mean duration of the observation period was 8.5±2.9 years.


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After adjusting for age, race/ethnicity, fracture prior to menopausal transition, cigarette use, body mass index, and study site, the results indicated that faster bone turnover during the menopausal transition increased the risk for incident fracture in postmenopause. Specifically, each standard deviation increment increase in the rate of bone turnover increased the hazard of incident fracture by 24% (P =.008).

The researchers also found that each standard deviation increment increase in the rate of bone turnover during early postmenopause was associated with a 27% greater hazard of fracture (P =.01)

Both of these associations remained significant after the researchers adjusted for absolute BMD in early menopause and rate of change in BMD during the menopausal transition.

The study had several limitations, including its use of urine NTX as the marker of bone turnover instead of serum levels of C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (PINP), which are the recommended markers for clinical studies. However, NTX was available in the SWAN dataset and deemed to be an acceptable marker by the researchers.

“[F]uture studies must… examine whether early, short-term anti-resorptive therapy in these women can indeed prevent the rapid increase in bone turnover during the [menopause transition],” the researchers wrote.

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Reference

Shieh A, Greendale GA, Cauley JA, Karlamangla AS. The association between fast increase in bone turnover during the menopause transition and subsequent fracture [published online December 16, 2019]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz281