Osteopontin in rheumatic diseases: A systematic review and meta-analysis

• Published in: Clinica chimica acta Vol. 570; p. 120209
• Main Authors: Zoroddu, Stefano, Lorenzo, Biagio Di, Paliogiannis, Panagiotis, Mangoni, Arduino A., Carru, Ciriaco, Zinellu, Angelo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.03.2025
• Subjects: Ankylosing spondylitis; Biomarkers; Biomarkers - blood; Connective tissue diseases; Humans; Osteoarthritis; Osteopontin; Osteopontin - blood; Rheumatic disease; Rheumatic Diseases - blood; Rheumatic Diseases - diagnosis; Rheumatic Diseases - metabolism; Rheumatoid arthritis; Systemic lupus erythematosus; Systemic sclerosis; Systemic lupus erythematosus; Connective tissue diseases; Rheumatoid arthritis; Systemic sclerosis; Osteopontin; Biomarkers; Osteoarthritis; Ankylosing spondylitis; Rheumatic disease
• ISSN: 0009-8981; 1873-3492; 1873-3492
• DOI: 10.1016/j.cca.2025.120209

•Elevated osteopontin (OPN) concentrations are strongly associated with rheumatic diseases (RDs).•Meta-analysis reveals a pooled standardized mean difference (SMD) of 1.54 for OPN concentrations in RDs versus controls.•Subgroup analysis shows consistent elevations in systemic lupus erythematosus (SMD = 0.97, I2 = 0 %) and rheumatoid arthritis (SMD = 0.70, I2 = 92.5 %).•Osteoarthritis displays the largest OPN effect size in synovial fluid (SMD = 5.83, I2 = 80.9 %).•Results emphasize OPN’s potential as a biomarker for RDs, particularly in systemic and local disease contexts. Osteopontin (OPN), a glycoprotein involved in immune regulation and inflammation, is a potential candidate biomarker for rheumatic diseases (RDs). However, variability across studies limits its clinical utility. This meta-analysis evaluated OPN concentrations in RD patients compared to healthy controls and explored sources of heterogeneity. A systematic search identified 37 studies (43 comparator groups) including 3,201 RD patients and 2,543 controls. Standardized mean differences (SMDs) were calculated, and subgroup and meta-regression analyses examined the modulating role of demographic and clinical variables. Publication bias was assessed using Begg’s and Egger’s tests. OPN concentrations were significantly higher in RD patients than controls (SMD = 1.54, 95 % CI: 1.17–1.90, p < 0.001). Subgroup analysis revealed consistent elevations in systemic lupus erythematosus (SLE, SMD = 0.97, I2 = 0 %) and rheumatoid arthritis (RA, SMD = 0.70, I2 = 92.5 %), with osteoarthritis showing the largest effect size (SMD = 4.02). Age significantly moderated OPN concentrations (p = 0.030). Although publication bias was detected (p < 0.05), removing seven studies eliminated bias and maintained significant between-group differences (SMD = 0.78, 95 % CI: 0.62–0.93; p < 0.001). The high concentrations of OPN support its possible use as a candidate biomarker for RDs, particularly in SLE and RA. Resolution of heterogeneity and standardization may improve its clinical utility.