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Genetic Perspective on the Relationship between Female Reproductive Traits, Exercise, and Bone Health Outcomes:
Bo-Kai Chen1, Jansen Marcos Cambia2, Chien-An Shih3,4
1School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Lifestyle Genomics
|July 10, 2026
Summary
Later natural menopause offers protection against osteoporosis in East Asian women, while exercise and genetic factors influence bone density. Personalized prevention strategies are recommended.
Area of Science:
- Genetics and Bone Health
- Reproductive Endocrinology
- Osteoporosis Research
Background:
- Female reproductive traits, influenced by estrogen, affect bone mineral density (BMD) and fracture risk.
- Causal links between reproductive traits and bone health are unclear due to confounding factors.
- Understanding these relationships is vital for effective osteoporosis prevention.
Purpose of the Study:
- To investigate the causal impact of age at natural menopause (ANM) and age at menarche (AAM) on BMD and osteoporosis risk.
- To explore gene-exercise interactions influencing bone health in East Asian women.
Main Methods:
- Two-sample Mendelian randomization (MR) was employed using genetic variants for AAM and ANM.
- Data from 51,049 East Asian women in the Taiwan Biobank were analyzed across discovery and validation cohorts.
- Outcomes included BMD Z-scores, T-scores, and clinical osteoporosis, with regression analyses for gene-exercise interactions.
Main Results:
- Later age at natural menopause (ANM) was causally linked to higher BMD and reduced osteoporosis risk.
- No consistent causal effect of age at menarche (AAM) on bone health was observed due to genetic pleiotropy.
- Both ANM polygenic risk scores and regular exercise independently improved BMD and reduced osteoporosis risk, with specific gene-exercise interactions identified.
Conclusions:
- Later ANM causally protects against osteoporosis in East Asian women; AAM effects were insignificant.
- Exercise positively impacts bone health, with benefits varying based on specific activities and genetic predispositions.
- Findings support personalized osteoporosis prevention through genetic risk assessment and tailored exercise recommendations.
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