Reproductive Factors Help Predict Fracture Risk in Aging Women

An analysis of nearly 1.3 million women is shedding light on how certain female reproductive factors can help predict increased risk of fracture among postmenopausal women.

Results of the analysis, which examined women from the Korean National Health Insurance Service database, suggest female reproductive factors are independent risk factors for fracture incidence and indicate shorter lifetime endogenous estrogen exposure was associated with higher risk of fracture.

“To our knowledge, this is the largest study performed to date to assess the association between female reproductive factors and fracture, especially according to skeletal site. We directly assessed fracture risk as a clinical outcome rather than BMD, which is a surrogate marker,” wrote study investigators.

With fractures posing a significant risk to the health and quality of life of aging women and previous research linking estrogen levels to fracture risk, a team from Seoul, Korea sought to determine how reproductive factors might influence fracture risk. With this in mind, investigators designed their analysis as a population-based retrospective cohort study using data from women within the Korean National Health Insurance Service database.

For inclusion in the analysis, women were required to have no previous fractures and have undergone both cardiovascular and breast and/or cervical cancer screening between January 1 and December 31, 2009.

Investigators first search yielded 3,109,506 women 40 years and older. After exclusion of patients based on history of fracture (111,764), those with a history of hysterectomy (215,083), and other factors, a cohort of 1,272,115 women was identified for inclusion in the final analysis. The mean age of the study cohort was 61.0 (SD, 8.1) years.

Data related to reproductive factors, including age at menarche, age at menopause, parity, breastfeeding, and exogenous hormone use, was obtained through questionnaires. For the purpose of the analysis, the incidence of any fractures and site-specific fractures were used as outcome measures.

Upon analysis, investigators found being aged 12 or younger at menarche rather than later age at menarche was associated with an increased risk of any fracture and vertebral fractures. Additionally, entering menopause at 40-54 years of age rather than at age 55 or later was associated with a lower risk of any fracture (aHR, 0.89; 95% CI, 0.86-0.93), vertebral fracture (aHR, 0.77; 95% CI, 0.73-0.81), and hip fracture (aHR, 0.89; 95% CI, 0.78-1.00).

Further analysis indicated a reproductive span of 40 years or longer was associated with lower risk of any fracture (aHR, 0.86; 95% CI, 0.84-0.88), vertebral fracture (aHR, 0.73; 95% CI, 0.71-0.76), and hip fracture (aHR, 0.87; 95% CI, 0.80-0.95) when compared to women with a reproductive age of less than 30 years. Investigators also found parous women who had given birth had a lower risk of any fracture than those who were considered nulliparous (aHR, 0.96; 95% CI, 0.92-0.99).

Results of the analysis indicated breastfeeding for 12 months or longer was associated with a higher risk of any fracture (aHR, 1.05; 95% CI, 1.03-1.08) and vertebral fractures (aHR, 1.22; 95% CI, 1.17-1.27) but a lower risk of hip fracture (aHR, 0.84; 95% CI, 0.76-0.93). Investigators pointed out receiving hormone therapy for 5 years or longer was associated with a lower risk of any fractures (aHR, 0.85; 95% CI, 0.83-0.88) and use of oral contraceptives for 1 year or longer was associated with an increased risk of any fractures (aHR, 1.03; 95% CI, 1.01-1.05).

“The clinical implications of our study are that menstrual and reproductive factors associated with reproductive hormonal disturbances, in particular late menarche, early menopause, and longer reproductive span, are potential risk factors for osteoporosis-related fractures,” wrote investigators.

This study, “Association of Female Reproductive Factors With Incidence of Fracture Among Postmenopausal Women in Korea,” was published in JAMA Network Open.