In:
Frontiers in Endocrinology, Frontiers Media SA, Vol. 15 ( 2024-5-21)
Abstract:
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. 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. Results Amongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P & lt;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 & lt;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 & lt;0.05). A significant non-linear dose–response was observed between CCR and osteoporosis/fracture risk ( P non-linearity & lt; 0.05). LDSC found no significant shared genetic effects by them, but PLACO identified 42 pleiotropic SNPs shared by CCR and fracture (P & lt;5×10– 8 ). MR analyses indicated the causal effect from CCR to osteoporosis/fracture. 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.
Type of Medium:
Online Resource
ISSN:
1664-2392
DOI:
10.3389/fendo.2024.1325320
DOI:
10.3389/fendo.2024.1325320.s001
DOI:
10.3389/fendo.2024.1325320.s002
DOI:
10.3389/fendo.2024.1325320.s003
DOI:
10.3389/fendo.2024.1325320.s004
DOI:
10.3389/fendo.2024.1325320.s005
DOI:
10.3389/fendo.2024.1325320.s006
DOI:
10.3389/fendo.2024.1325320.s007
DOI:
10.3389/fendo.2024.1325320.s008
DOI:
10.3389/fendo.2024.1325320.s009
DOI:
10.3389/fendo.2024.1325320.s010
DOI:
10.3389/fendo.2024.1325320.s011
DOI:
10.3389/fendo.2024.1325320.s012
DOI:
10.3389/fendo.2024.1325320.s013
DOI:
10.3389/fendo.2024.1325320.s014
DOI:
10.3389/fendo.2024.1325320.s015
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2024
detail.hit.zdb_id:
2592084-4
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