Correlation between serum bone remodeling biomarkers and CTX-1 levels among patients with rheumatoid arthritis: A cross-sectional study at a provincial referral hospital in Indonesia

Abstract

Rheumatoid arthritis (RA) is associated with accelerated bone loss, partly mediated by dysregulation of the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway, which regulates osteoclast activity. Carboxy-terminal cross-linked telopeptide of type I collagen (CTX-1) is a biochemical marker of bone resorption and may reflect increased skeletal turnover in RA. Although previous studies have evaluated RANKL, OPG, and the RANKL/OPG ratio in relation to bone mineral density, osteoporosis, and fracture risk, the correlations of circulating RANK, RANKL, and OPG with CTX-1 remain insufficiently characterized in patients with RA. The aim of this study was to evaluate the correlations of serum RANK, RANKL, and OPG levels with serum CTX-1 levels in patients with RA. An analytical cross-sectional study was conducted at a provincial referral hospital in Padang, Indonesia, from July to December 2024, during which patients with RA were recruited through consecutive sampling. Serum RANK, RANKL, OPG, and CTX-1 concentrations were measured using enzyme-linked immunosorbent assays. Correlations were assessed using Pearson’s correlation analysis. The mean age of the patients was 40.30±5.08 years. The mean serum concentrations of RANK, RANKL, OPG, and CTX-1 were 5.20±2.83, 6.55±3.14, 0.17±0.09, and 2.10±1.10 ng/mL, respectively. Serum RANK and RANKL levels showed very strong positive correlations with CTX-1 levels (r=0.928 and r=0.929, respectively; both p<0.001). Serum OPG levels also showed a strong positive correlation with CTX-1 levels (r=0.786; p<0.001). These findings suggest that circulating components of the RANK/RANKL/OPG pathway are associated with biochemical bone resorption in patients with RA. However, a larger longitudinal study incorporating disease activity, treatment exposure and bone mineral density is required to determine their clinical relevance.