# Beyond linearity: a threshold effect links serum creatinine to SIRI in osteoporotic fractures

**Authors:** Shuai Yuan, Ke Lu, Xiao-jie Zhou, Hao-tian Jiao, Yue-qin Guo, Chong Li

PMC · DOI: 10.3389/fmed.2025.1710691 · Frontiers in Medicine · 2025-12-18

## TL;DR

This study finds a threshold effect where higher serum creatinine levels above 78 μmol/L are linked to increased inflammation in patients with osteoporotic fractures.

## Contribution

The study identifies a non-linear, threshold relationship between serum creatinine and SIRI in osteoporotic fracture patients.

## Key findings

- Serum creatinine is independently and positively associated with SIRI in OPF patients.
- A threshold effect occurs at 78 μmol/L, with stronger association above this level.
- Each 1 μmol/L increase in creatinine above threshold raises SIRI by 0.033.

## Abstract

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.

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.

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).

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.

## Linked entities

- **Diseases:** diabetes (MONDO:0005015), heart disease (MONDO:0005267), chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Genes:** SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}
- **Diseases:** diabetes (MESH:D003920), inflammatory (MESH:D007249), OPF (MESH:D058866), hypertension (MESH:D006973), heart disease (MESH:D006331), CKD (MESH:D051436)
- **Chemicals:** triglycerides (MESH:D014280), TC (-), alcohol (MESH:D000438), phosphorus (MESH:D010758), cholesterol (MESH:D002784), creatinine (MESH:D003404)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12756718/full.md

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Source: https://tomesphere.com/paper/PMC12756718