| Title: | Plasma proteins mediate the protective association between physical activity and osteoporosis risk: A prospective study in the UK biobank |
| Journal: | Archives of Gerontology and Geriatrics |
| Published: | 15 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42001538/ |
| DOI: | https://doi.org/10.1016/j.archger.2026.106240 |
Publication 17988
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Abstract
BACKGROUND: This study examined the association between physical activity (PA) and osteoporosis risk and, using plasma proteomics and mediation analysis, identified circulating proteins and pathways that mediate this relationship.</p>
METHODS: We included 39,799 UK Biobank participants free of osteoporosis at baseline. Cox regression models assessed associations between PA and incident osteoporosis. Linear regression identified PA-associated proteins, and enrichment analysis characterised their functional pathways. Taking moderate-to-vigorous physical activity (MVPA) categories as the exposure, causal mediation analysis within a Cox framework estimated the total effect (TE), pure natural direct effect (PNDE), pure natural indirect effect (PNIE), and proportion mediated (PM). Proteins with significant mediation effects underwent pathway enrichment analysis.</p>
RESULTS: Over a mean follow-up of 13.1 years, 1589 participants developed osteoporosis. After multivariable adjustment, moderate and high MVPA were associated with lower osteoporosis risk (HR=0.75, 95% CI 0.64-0.88; HR=0.74, 95% CI 0.63-0.87), whereas the association for low MVPA was weaker. Restricted cubic splines showed that, compared with 0 MET-min/week, MVPA in the range of approximately 500-7000 MET-min/week was associated with the lowest risk, with little additional benefit at higher levels. We identified 60 proteins (PM ≥ 5%) that mediated the MVPA-osteoporosis association, mainly enriched in cytokine-cytokine receptor interaction and PI3K-Akt signaling.</p>
CONCLUSION: PA is inversely associated with osteoporosis risk. Plasma proteins involved in immune/inflammatory regulation, mechanotransduction signaling, and the PI3K-Akt signaling pathway exerted significant mediating effects in this association. These proteins represent candidates for further investigation in studies designed to establish causality and clinical utility.</p>
11 Authors
- Binbin Liu
- Shicheng Luo
- Ziming Geng
- Xiaopeng Jia
- Hongji Wang
- Ze Pei
- Tianran Tang
- Xiaopei Yang
- Gongzi Zhang
- Shuwei Zhang
- Lihai Zhang
1 Application
| Application ID | Title |
|---|---|
| 716731 | Assessing Optimal Treatment Protocols for Pelvic Fractures in Motor Vehicle Accident Patients |
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