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Background <p>Early immuno-inflammatory response serves a critical role in the process of fracture healing, and both excessive and insufficient activation after injury may predict adverse outcomes. This study aimed to investigate the association between post-injury high-sensitivity C-reactive protein to lymphocyte ratio (HCLR) and nonunion.</p> Methods <p>This multicenter retrospective cohort study included adult patients who underwent orthopedic surgery for limb fractures at five tertiary hospitals in China between January 2020 and December 2022. Exposure variable was post-injury HCLR level, calculated by dividing high-sensitivity C-reactive protein by lymphocyte count. The primary outcome was extremity fracture nonunion, which was defined as absence of union ≥ 9 months after injury with no radiographic progression toward healing during the preceding 3 months, and which was ascertained through comprehensive chart review, structured medical records, telephone follow-ups, and outpatient assessments. The association between HCLR and nonunion was estimated using restricted cubic spline (RCS) curve and multivariate logistic regression to adjust for potential confounders.</p> Results <p>In total, 27,941 patients were included (aged 49.5 ± 16.5 years, 59.9% male). Nonunion occurred in 598 patients (2.1%). RCS analysis showed a non-linear relationship between HCLR and nonunion risk; and the cutoff value for the risk-protective effect of HCLR on nonunion was 6.5. Compared to high HCLR level (≥ 6.5), lower HCLR level (&lt; 6.5) was significantly associated with higher nonunion risk (odds ratio [<i>OR</i>] = 2.092; 95% CI, 1.763–2.483); and this association persisted after adjustment for a range of confounders (adjusted <i>OR</i> = 2.305; 95% CI, 1.846–2.877). Subgroup analyses showed heterogeneous results in terms of surgery site and fixation methods (<i>P for interaction</i> &lt; 0.050).</p> Conclusion <p>In patients with surgically treated extremity fractures at low risk of nonunion, lower post-injury HCLR levels were associated with a higher risk of nonunion. HCLR may serve as a candidate adjunctive biomarker reflecting the early systemic inflammatory and immune status. These findings require further confirmation through external validation of the threshold and mechanistic studies to clarify the biological basis of this association.</p>

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Post-injury high-sensitivity C-reactive protein to lymphocyte ratio and nonunion risk in adult extremity fractures: evidence from a multicenter retrospective cohort

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  • 发表日期：

    2026年7月31日

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  • Zhenbang Yang,
  • Tianwei An,
  • Xiangcheng Gao,
  • Puxin Yang,
  • Chengsi Li,
  • Zhiqiang Li,
  • Tianrui Wang,
  • Baorui Xing,
  • Yubin Long,
  • Yanbin Zhu,
  • Yingze Zhang,
  • Wei Chen

摘要

Background

Early immuno-inflammatory response serves a critical role in the process of fracture healing, and both excessive and insufficient activation after injury may predict adverse outcomes. This study aimed to investigate the association between post-injury high-sensitivity C-reactive protein to lymphocyte ratio (HCLR) and nonunion.

Methods

This multicenter retrospective cohort study included adult patients who underwent orthopedic surgery for limb fractures at five tertiary hospitals in China between January 2020 and December 2022. Exposure variable was post-injury HCLR level, calculated by dividing high-sensitivity C-reactive protein by lymphocyte count. The primary outcome was extremity fracture nonunion, which was defined as absence of union ≥ 9 months after injury with no radiographic progression toward healing during the preceding 3 months, and which was ascertained through comprehensive chart review, structured medical records, telephone follow-ups, and outpatient assessments. The association between HCLR and nonunion was estimated using restricted cubic spline (RCS) curve and multivariate logistic regression to adjust for potential confounders.

Results

In total, 27,941 patients were included (aged 49.5 ± 16.5 years, 59.9% male). Nonunion occurred in 598 patients (2.1%). RCS analysis showed a non-linear relationship between HCLR and nonunion risk; and the cutoff value for the risk-protective effect of HCLR on nonunion was 6.5. Compared to high HCLR level (≥ 6.5), lower HCLR level (< 6.5) was significantly associated with higher nonunion risk (odds ratio [OR] = 2.092; 95% CI, 1.763–2.483); and this association persisted after adjustment for a range of confounders (adjusted OR = 2.305; 95% CI, 1.846–2.877). Subgroup analyses showed heterogeneous results in terms of surgery site and fixation methods (P for interaction < 0.050).

Conclusion

In patients with surgically treated extremity fractures at low risk of nonunion, lower post-injury HCLR levels were associated with a higher risk of nonunion. HCLR may serve as a candidate adjunctive biomarker reflecting the early systemic inflammatory and immune status. These findings require further confirmation through external validation of the threshold and mechanistic studies to clarify the biological basis of this association.