Background/Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction and disability. Previous studies showed abnormal activation of osteoclasts as well as altered skeletal bone metabolism and co-morbid conditions in RA. Tumor necrosis factor receptor-associated factor (TRAF) 6 is one of the critical modulator in differentiation and resorption activity of osteoclasts. New biochemical markers of bone formation showed contradictory results in different studies, although markers of bone resorption have shown significant increase in patients with RA. This study aimed to evaluate serum levels of bone metabolism markers and their correlation with synovial TRAF6 expression, as well as clinical and biological parameters that reflect the activity and severity of RA.

Methods: Serum C-terminal telopeptide of type I collagen (CTX-I), N-terminal propeptide of type I collagen (PINP) and N-terminal midfragment of Osteocalcin (N-MID.OC) was tested by chemiluminescence in 30 patients with active RA, as well as 60 age and gender matched healthy controls. Synovial tissue samples were obtained by needle biopsy from RA patients, and semiquantitative analysis was performed to evaluate the intensity of TRAF6+ cells. Serological and clinical parameters that reflect the activity and severity of RA, as well as radiographic joint destruction (Sharp score) were collected simultaneously.

Results: Serum CTX-I level was significantly higher in RA patients compared with healthy controls (0.56±0.37 vs. 0.34±0.21, p=0.004). No significant difference was found in serum PINP or N-MID.OC level. Spearman’s correlation test showed serum PINP and N-MID.OC level of RA patients correlated negatively with morning stiffness (r=–0.450 and –0.267, p=0.016 and 0.046, respectively) and pain VAS (r=–0.247 and –0.354, p=0.049 and 0.045, respectively), but correlated positively with gripping power (r=0.676 and 0.621, p=0.005 and 0.006, respectively). Significant correlation was found between synovial TRAF6 expression and serum PINP level (r=0.381, p=0.038), as well as serum N-MID.OC level (r=0.345, p=0.042). Subanalysis of lining and sublining TRAF6 expression showed that PINP correlated significantly with sublining TRAF6 expression (r=0.353, p=0.046), N-MID.OC correlated significantly with lining TRAF6 expression (r=0.407, p=0.025).

Conclusion: Increased bone resorption and altered skeletal bone metabolism was found in RA. PINP and N-MID.OC may be a helpful biomarker for disease activity in RA. Synovial TRAF6 expression in RA correlated significantly with serum PINP and N-MID.OC level and maybe involved in the pathogenesis of bone metabolism disbalance in RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/altered-serum-levels-of-bone-metabolism-markers-in-rheumatoid-arthritis/