Beyond Linearity: A Threshold Effect Links Serum Creatinine to SIRI in Osteoporotic Fractures

Shuai Yuan¹Ke Lu¹Xiao-jie Zhou¹Hao-tian Jiao¹Yue-qin Guo²Chong Li^1*

• ¹Affiliated Kunshan hospital of Jiangsu University, Suzhou, China
• ²The Fifth People's Hospital Kunshan, Suzhou, China

Introduction: There is a scarcity of research examining the association between serum creatinine and the systemic inflammatory response index (SIRI) in individuals with osteoporotic fractures (OPF). Understanding this link may improve perioperative risk stratification and inflammatory management in OPF inpatients. Consequently, we explored the independent association between serum creatinine and SIRI and assessed potential non-linear or threshold effects in hospitalized OPF patients. Methods: A retrospective cross-sectional analysis was performed on 2,135 individuals with OPF who needed surgical intervention or inpatient care at affiliated Kunshan Hospital of Jiangsu University from January 2017 to August 2023. The exposure was serum creatinine and the outcome was SIRI. Covariates included age, sex, body mass index (BMI), hypertension, diabetes, heart disease, chronic kidney disease (CKD), alcohol consumption, smoking status, phosphorus, total cholesterol (TC), triglycerides, and aspartate aminotransferase (AST). Associations were estimated using multivariable linear regression and generalized estimating equations (GEE). Nonlinearity was examined using generalized additive models (GAMs) with smooth curve fitting and threshold (piecewise) analysis; univariable analyses were also performed. Results: After multivariable adjustment, serum creatinine was independently and positively associated with SIRI (β, 0.013; 95% CI, 0.004, 0.021, P-value < 0.01). GAM indicated a significant threshold effect (P-value for LRT = 0.02) with an inflection at 78 µmol/L. Above this threshold, the association strengthened (β, 0.033; 95% CI, 0.014, 0.052, P-value < 0.01) Conclusion: Among hospitalized patients with OPF, higher serum creatinine is associated with higher SIRI, with a clinically relevant threshold at 78 µmol/L. For creatinine values above this threshold, each 1 µmol/L increment corresponds to a 0.033 increase in SIRI. These findings support routine monitoring of creatinine, inflammatory status, and renal function in this population and warrant confirmation in prospective studies.