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. 2025 Jul;44(7):2993-3001.
doi: 10.1007/s10067-025-07517-6. Epub 2025 Jun 3.

Association between serum creatinine/cystatin C ratio and symptomatic knee osteoarthritis incidents in Chinese middle-aged and older adults, considering sex variations: findings from the CHARLS

Boran Sun  1 , Aerman Nuer  1 , Lemeng Ma  1 , Yasi Yang  1 , Wenbo Xiao  1 , Huanli Jiao  2 , Xiaochen Huai  3 , Yun Zhu  1 , Yuan Wang  1 , Yongjie Chen  1 , Wenli Lu  4
Affiliations

Association between serum creatinine/cystatin C ratio and symptomatic knee osteoarthritis incidents in Chinese middle-aged and older adults, considering sex variations: findings from the CHARLS

Boran Sun et al. Clin Rheumatol. 2025 Jul.

Abstract

Introduction/objectives: Symptomatic knee osteoarthritis (KOA) and muscle-related disorders are prevalent and interrelated among middle-aged and elderly people. Serum creatinine/cystatin C (Cr/CysC) ratio is a promising biomarker for identifying low muscle mass or sarcopenia. The aim of this study was to investigate the association between serum Cr/CysC and the incident risk of symptomatic knee osteoarthritis in Chinese middle-aged and older adults, considering sex variations.

Methods: This prospective cohort study included 4155 participants aged ≥ 45 years from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). Cr/CysC ratio was calculated by serum creatinine (mg/dL)/cystatin C (mg/L) *100. The incidence of symptomatic KOA was defined as participants who were free of symptomatic KOA at baseline and diagnosed with symptomatic KOA at the 4-year follow-up. Logistic regression models were used to explore the relationship between Cr/CysC ratio and incidence of KOA in both sexes. Restricted cubic analysis was employed to analyze the nonlinear relationship.

Results: Then, 420 participants (10.1%) developed KOA during the 4-year follow-up. Higher Cr/CysC ratio was associated with a lower risk of symptomatic KOA incidents (per 1 SD increase, OR = 0.85, 95% CI = 0.74-0.98, P < 0.001), with significant effect modification by sex (P-interaction = 0.013). The highest tertile of Cr/CysC ratio was significantly linked with a lower incidence of symptomatic KOA in males (OR = 0.50, 95% CI = 0.29-0.88, P = 0.015), but not in females (OR = 0.88, 95% CI = 0.61-1.29, P = 0.522) compared with the lowest tertile. A significant nonlinear relationship was identified for males, with 75.0 of Cr/CysC ratio being an inflection point.

Conclusions: Our findings provided new insights that the Cr/CysC ratio might serve as a promising biomarker for KOA among Chinese males. The clinical utility of applying the Cr/CysC ratio to routine clinical screening for KOA warranted further strictly designed randomized controlled trials and health economics studies. Key points • This study elucidated the longitudinal association between serum creatinine/cystatin C (Cr/CysC) ratio and symptomatic knee osteoarthritis (KOA) and sex differences among middle-aged and older Chinese people. • There was a significant relationship between the lower Cr/CysC ratio and increasing risk of symptomatic KOA in males, but not in female adults. A significant nonlinear relationship was identified for males, with 75.0 of the Cr/CysC ratio being an inflection point. • Cr/CysC ratio may serve as a biomarker for predicting the risk of symptomatic KOA in Chinese middle-aged and older males.

Keywords: Biomarker; China health and retirement longitudinal study; Creatinine; Cystatin C; Symptomatic knee osteoarthritis.

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Conflict of interest statement

Compliance with ethical standards. Ethics approval and consent to participate: The present study was approved by the Peking University Biomedical Ethics Review Committee (IRB00001052-11015). Participants provided written informed consent for this study. All procedures performed were in accordance with the 1964 Declaration of Helsinki ethical standards and its later amendments. Consent for publication: Not applicable. Disclosures: None.

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