| Title: | Serum creatinine, genetic susceptibility, and the risk of osteoporosis and fracture: a prospective cohort study from the UK Biobank |
| Journal: | Frontiers in Endocrinology |
| Published: | 20 Jan 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41641030/ |
| DOI: | https://doi.org/10.3389/fendo.2025.1727636 |
| URL: | https://public-pages-files-2025.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1727636/pdf |
Publication 18605
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Background: Osteoporosis imposes a substantial fracture burden, yet scalable and dynamic biomarkers for risk stratification remain limited. Serum creatinine-routinely assayed and capturing intertwined muscle and renal signals-has been little studied for incident osteoporosis or fractures.</p>
Methods: In the UK Biobank, covariate-adjusted Cox models and restricted cubic splines assessed associations of baseline creatinine with incident osteoporosis and fractures. Creatinine was modeled categorically (six strata; G4 [70-80 μmol/L] as reference) and continuously. The pre-defined analysis was stratified by sex and age (>65) as well as the three tertiles of the polygenic risk score for osteoporosis (PRS); the multiplicative interaction term examined the relationship between creatinine and PRS.</p>
Results: Creatinine showed a U-shaped association with osteoporosis, with a nadir near 80 μmol/L (overall P<0.001; nonlinearity P<0.001). In piecewise models, each 1-μmol/L increase corresponded to a 2.0% lower osteoporosis risk within 25-80 μmol/L (HR = 0.980, 95% CI 0.978-0.982) and a 1.1% higher risk within 80-130 μmol/L (HR = 1.011, 95% CI 1.006-1.017). For fractures, the dose-response was J-shaped around the same nadir: risk decreased by 1.0% per μmol in 25-80 μmol/L (HR = 0.990, 95% CI 0.988-0.992) and increased by 0.3% per μmol in 80-130 μmol/L (HR = 1.003, 95% CI 0.999-1.006). Sex-stratified patterns were directionally concordant. In PRS-stratified categorical analyses (vs G4), the low-creatinine stratum (G1) carried higher osteoporosis risk across tertiles (HRs 1.925, 1.811, and 1.592 for low, intermediate, and high PRS). Creatinine×PRS interactions were not significant (osteoporosis P = 0.132; fractures P = 0.210).</p>
Conclusions: Baseline serum creatinine was significantly and nonlinearly associated with incident osteoporosis (U-shaped pattern) and fractures (J-shaped pattern), with the lowest risk observed at approximately 80 μmol/L, and there was a notable sex difference (higher in males). These associations were independent of genetic susceptibility, suggesting that serum creatinine may serve as a low-cost adjunct marker for clinical risk stratification and surveillance of osteoporosis.</p>
17 Keywords
- Aged
- Biological Specimen Banks
- Biomarkers
- Creatinine
- Female
- Follow-Up Studies
- Fractures, Bone
- Genetic Predisposition to Disease
- Humans
- Male
- Middle Aged
- Osteoporosis
- Osteoporotic Fractures
- Prospective Studies
- Risk Factors
- UK Biobank
- United Kingdom
9 Authors
- Weijie He
- Yu Zhou
- Jiaxuan Ding
- Jiale Jiang
- Hang Zhang
- Chonghui Hu
- Qiongyan Liu
- Honglin Gu
- Huimou Chen
1 Application
| Application ID | Title |
|---|---|
| 85224 | Identification of risk factors and construction of early-diagnosis model for predicting the risk of pancreatic cancer in new-onset diabetes population based on UK Biobank data |
Enabling scientific discoveries that improve human health