This research, undertaken under the auspices of the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE), combined data from 141,222 naturally postmenopausal women from five cohorts. It was designed to test two overarching hypotheses: whether reproductive difficulties like infertility, miscarriage, stillbirth, and low parity are related to elevated risk of osteoporosis, and whether menopausal age might explain these relationships.
This pooled analysis employed retrospective and prospective data from five cohorts from around the world who belonged to the InterLACE consortium. Excluding women who had undergone unnatural menopause and those for whom reproductive history, osteoporosis status, and covariates were incomplete, the researchers included only those women who met these criteria. Major exposures to infertility, miscarriage, stillbirth, and parity were reported by participants themselves.
Diagnoses of osteoporosis were derived from various sources of data, such as surveys, hospital discharge records, death registers, primary care data, and records of drug use. Cox regression models were used by researchers to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between factors related to fertility and osteoporosis risk. Models were also adjusted for key covariates including race, age, education, smoking, alcohol consumption, BMI, physical activity, and age at menarche, with a further step adjusting for age at natural menopause as a time-varying covariate.
Key Findings
Modest but persistent elevated risks of osteoporosis in women with unfavorable reproductive histories were found by the study:
Infertility history was linked with a 16% increased risk of osteoporosis (HR=1.16, 95% CI: 1.13–1.19).
Women with three or more miscarriages had 17% increased risk (HR=1.17, 95% CI: 1.05–1.30).
Those who had stillbirth had 14% increased risk (HR=1.14, 95% CI: 1.10–1.17).
No live births: HR=1.20 (95% CI: 1.15–1.25)
One live birth: HR=1.15 (95% CI: 1.14–1.16)
This big international study verifies that infertility, habitual miscarriage, stillbirth, and low parity are associated with higher risk of osteoporosis in naturally postmenopausal women. These relationships remained significant even after controlling for age at menopause, indicating an independent contribution of reproductive factors in bone health. Physicians can think of these reproductive markers as preliminary indicators for osteoporosis risk assessment and individualized prevention measures.
Reference:
Chen, L. I. A. N. G., Chung, H.-F., Anderson, D. J., VAN DER Schouw, Y. T., Avis, N. E., Karvonen-Gutierrez, C. A., Dobson, A. J., & Mishra, G. D. (2025). The association of infertility, miscarriage, stillbirth, and parity with osteoporosis: a pooled analysis of five cohort studies. Fertility and Sterility. https://doi.org/10.1016/j.fertnstert.2025.07.382
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