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. 2025 Sep 17:16:1666884.
doi: 10.3389/fimmu.2025.1666884. eCollection 2025.

Neutrophil-to-albumin ratio: a novel predictor of osteoporosis in rheumatoid arthritis

Yifang Zhang #  1   2 , Zhongyu He #  1 , Kaiqiang Li #  1 , Qiuping Wu  1 , Shigang Wang  1 , Minying Liu  1   3 , Qingping Liu  3 , Qiang Xu  3 , Xiangying Kong  4 , Changsong Lin  3
Affiliations

Neutrophil-to-albumin ratio: a novel predictor of osteoporosis in rheumatoid arthritis

Yifang Zhang et al. Front Immunol. .

Abstract

Background: Osteoporosis (OP) frequently coexists with rheumatoid arthritis (RA), but validated predictors of early risk are not extensively studied. This study seeks to examine the relationship between the neutrophil percentage-to-albumin ratio (NPAR) and the likelihood of developing RA-related OP(RA-OP).

Methods: After investigating the relationship between the NPAR and RA-OP in the clinical retrospective study, we further validated this association using data from the National Health and Nutrition Examination Survey (NHANES) database (2005-2020 cycles). This retrospective study enrolled 718 RA patients from the Rheumatology Department of the First Affiliated Hospital of Guangzhou University of Chinese Medicine between January 2020 and December 2024. Patients were categorized into low-NPAR (<1.7598) and high-NPAR (≥1.7598) groups based on the median NPAR. Extracted clinical data encompassed demographic characteristics, comorbidities, serological markers, and other laboratory parameters. Preliminary univariate and multivariate logistic regression analyses assessed potential associations between NPAR and RA-OP, multi-model adjusted logistic regression was subsequently applied to evaluate the independent association, subgroup analyses examined consistency across demographic and clinical strata, Receiver operating characteristic (ROC) curve analysis assessed NPAR's diagnostic performance, and then Restricted cubic splines (RCS) visualized potential non-linear relationships. Finally using the identical statistical framework, we validated findings within the NHANES cohort.

Results: The high-NPAR group exhibited significantly higher OP incidence than the low-NPAR group (39.0% vs. 26.5%; P<0.001). After full adjustment (Model 4), NPAR remained independently associated with increased RA-OP risk as a categorical variable (high vs. low NPAR: adjusted OR = 1.70 (95%CI: 1.01~2.88); P = 0.049). Subgroup analyses demonstrated no significant interaction effects (P-interaction>0.05) except for disease duration. The ROC curve showed an Area Under the Curve(AUC) of 0.58 (95%CI: 0.53~0.63) and NPAR cut-off of 1.886. The covariate-adjusted RCS indicated a linear dose-response relationship (P overall=0.033; P nonlinearity=0.168). NHANES cohort analysis independently validated both the NPAR-RA-OP association and its linear characteristic.

Conclusion: NPAR, serving as a novel composite biomarker integrating neutrophil-mediated inflammation and nutritional status (via albumin), independently predicts OP risk in RA. Its derivation from routine clinical parameters renders NPAR a readily deployable, cost-effective tool for OP risk stratification in clinical practice.

Keywords: National Health and Nutrition Examination Survey; inflammation; neutrophil percentage to albumin ratio; osteoporosis; rheumatoid arthritis; risk stratification.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow Diagram of Study Population Selection.
Figure 2
Figure 2
Subgroup Analysis of the Association between NPAR and RA-OP Risk.
Figure 3
Figure 3
ROC curves of NPAR for predicting RA-OP risk.
Figure 4
Figure 4
RCS illustrating the relationship between NPAR and RA-OP: (A) unadjusted RCS, (B) covariate-adjusted RCS.
See this image and copyright information in PMC

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