Related Experiment Videos
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.
Introduction:
Female reproductive traits influence bone mineral density (BMD) and fracture risks through estrogen exposure. However, these causal relationships remain unclear due to confounding. Understanding these relationships is crucial for osteoporosis prevention strategies. This study aimed to investigate the causal impact of age at natural menopause (ANM) and age at menarche (AAM) on BMD and osteoporosis risk, and to explore gene-exercise interactions influencing bone health in East Asian women.
Methods:
We conducted two-sample Mendelian randomization (MR) using 15 genetic variants for AAM and 36 variants for ANM in 51,049 women from the Taiwan Biobank, split into discovery (n = 25,549) and validation (n = 25,500) cohorts. Outcomes were BMD Z scores, T scores, and clinical osteoporosis. We performed univariable and multivariable MR, followed by regression analyses, focusing on exercise effects on BMD and genetic predisposition scores for AAM and ANM.
Results:
In multivariable MR, genetically determined later ANM was associated with higher BMD Z scores (β = 0.045, 95% confidence interval [0.021, 0.069]), higher T scores (β = 0.046, [0.020, 0.072]), and lower osteoporosis risk (β = -0.106, [-0.154, -0.058]). No consistent causal effect was observed for AAM due to genetic pleiotropy. ANM polygenic risk score and regular exercise were independently associated with improved BMD Z- and T scores and reduced risk of osteoporosis. Specific gene-exercise interactions were identified in which the AAM polygenic risk score interacted significantly with gymnastics, while the ANM polygenic risk score interacted with lower-limb exercise and swimming.
Conclusion:
Late ANM provides causal protection against osteoporosis in East Asian women, while the effects of AAM remain insignificant. Exercise benefits bone health with activity-specific genetic interactions. These findings support personalized osteoporosis prevention strategies incorporating both genetic risk assessment and targeted exercise recommendations, particularly for women with early menopause predisposition.
Related Concept Videos
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:25Role of Vitamins in Maintaining Bone Health
Vitamin A
Vitamin A is involved in the process of bone remodeling. Retinoic acid, the active metabolite of Vitamin A, has nuclear receptors in osteoblasts and osteoclasts, which are involved in bone remodeling.
Vitamin B12
Vitamin B12 acts as a cofactor during the formation of osteoblast-related proteins, such as osteocalcin. Vitamin B12 plays a role...
01:20Introduction to the Skeletal System
Components of the Skeletal System
Bone, or osseous tissue, is a hard connective tissue that forms an internal support structure for the human body. Bones shield vulnerable organs and soft tissue from external forces. For example, the vertebral bones protect and support the spinal cord.
Cartilage, a semi-rigid connective tissue found in regions such as...
01:09Changes in the Appendicular Skeleton with Age
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying...
01:20Study Designs in Epidemiology
Observational studies are those where the researcher does not intervene but rather observes natural variations. They include cross-sectional, cohort, and case-control studies.