Background: Bone metabolism is disrupted in rheumatoid arthritis (RA); however, the bone metabolic signature of RA is poorly known.

Objectives: The objective of the study is to further characterize the bone metabolic profile of RA and compare it to psoriatic arthritis (PsA), systemic sclerosis (SSc) and healthy controls.

Methods: We did a cross-sectional case-control study on consecutively enrolled patients and age-matched controls. We collected clinical characteristics, serum biomarkers related to bone metabolism and Bone Mineral Density (BMD). A multiple correlation analysis using Spearman’s rank correlation coefficient was conducted within the RA patient group to investigate associations between biomarker levels and clinical variables. Machine learning (ML) models and Principal Component Analysis (PCA) was performed to evaluate the ability of bone biomarker profiles to differentiate RA patients from controls. We ran three different ML models (random forest, neural network, logistic regression) considering the following features in addition to all serum biomarkers tested: cumulative glucocorticoid intake, age, gender, CRP levels, csDMARD and b/tsDMARD use. To assess the performance of these machine learning models, we employed standard evaluation metrics, including classification accuracy (CA), precision, recall, and receiver operating characteristic (ROC) curves with area under the curve (AUC) analysis. We implemented cross-validation (10 folds, stratified) to ensure the robustness of our models and mitigate overfitting.

Results: A total of 1883 participants were included in the analysis, comprising 1462 Rheumatoid Arthritis (RA) patients, 60 Psoriatic Arthritis (PsA) patients, 62 Systemic Sclerosis (SSc) patients, and 359 age-matched healthy controls. We found significantly lower BMD in RA patients compared to PsA, and Systemic Sclerosis SSc groups. RA patients exhibited higher Dkk1, sclerostin and lower P1nP and B-ALP levels compared to controls. No significant differences in CTX levels were noted. Figure 1 shows the relevant markers. Correlation analysis revealed associations between bone biomarkers and clinical variables ( Figure 2A ). PCA and ML highlighted distinct biomarker patterns in RA which can effectively discriminated bone biomarkers profile in RA from controls ( Figure 2B ).

Figure 1.

Figure 2.

Conclusion: Our study helped uncover the distinct bone profile in RA, including changes in bone density and unique biomarker patterns. These findings enhance our comprehension of the intricate links between inflammation, bone dynamics, and RA activity, offering potential insights for diagnostic and therapeutic advancements in managing bone involvement in this challenging condition.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Giovanni Adami Theramex, UCB, Lilly, Galapagos, Fresenius Kabi, Amgen, BMS, Abiogen and Pfizer, Angelo Fassio: None declared, Ombretta Viapiana: None declared, Camilla Benini: None declared, Davide Gatti: None declared, Maurizio Rossini: None declared.