| Title: | Muscle-origin creatinine-cystatin C ratio is an osteoporosis marker in individuals with normal renal function: evidence from observational and Mendelian randomization analysis |
| Journal: | Frontiers in Endocrinology |
| Published: | 21 May 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38836225/ |
| DOI: | https://doi.org/10.3389/fendo.2024.1325320 |
| URL: | http://dx.doi.org/10.3389/fendo.2024.1325320 |
Publication 12018
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Abstract
Background: Creatinine-cystatin C ratio (CCR) has been demonstrated as an objective marker of sarcopenia in clinical conditions but has not been evaluated as an osteoporosis marker in individuals with normal renal function.</p>
Methods: We selected 271,831 participants with normal renal function from UK Biobank cohort. Multivariable linear/logistic regression and Cox proportional hazards model were used to investigate the phenotypic relationship between CCR and osteoporosis in total subjects and gender-stratified subjects. Based on the genome-wide association study (GWAS) data, linkage disequilibrium regression (LDSC) and Mendelian randomization (MR) analysis were performed to reveal the shared genetic correlations and infer the causal effects, respectively.</p>
Results: Amongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P<0.05). The multivariable logistic regression model showed that the decrease in CCR was associated with a higher risk of osteoporosis/fracture in all models (all P<0.05). In the multivariable Cox regression analysis with adjustment for potential confounders, reduced CCR is associated with the incidence of osteoporosis and fracture in both total subjects and gender-stratified subjects (all P<0.05). A significant non-linear dose-response was observed between CCR and osteoporosis/fracture risk (P non-linearity < 0.05). LDSC found no significant shared genetic effects by them, but PLACO identified 42 pleiotropic SNPs shared by CCR and fracture (P<5×10-8). MR analyses indicated the causal effect from CCR to osteoporosis/fracture.</p>
Conclusions: Reduced CCR predicted increased risks of osteoporosis/fracture, and significant causal effects support their associations. These findings indicated that the muscle-origin serum CCR was a potential biomarker to assess the risks of osteoporosis and fracture.</p>
9 Authors
- Pei He
- Yi-Qun Yang
- Han Wang
- Ya-Qian Zhang
- Yu-Ni Gu
- Chen-Cheng Hong
- Lin Bo
- Fei-Yan Deng
- Shu-Feng Lei
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