Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation, under the control of pro-inflammatory cytokines, including TNFα. Therefore, we tested the hypothesis that administration of infliximab, an anti-TNFα drug in the treatment of RA would modulate both systemic and local bone resorption and reduce cartilage degradation. We performed a prospective study of a multicentric cohort of 48 women, mean age 54.2±12.1 years old, with severe RA for 11.4±7.8 years, who started infliximab after failure of other disease-modifying antirheumatic drugs. At baseline and 6, 22 and 54 weeks after initiating Infliximab therepy we measured the following biochemical markers: serum type I procollagen N-terminal propeptide (PINP), a marker of bone formation, serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), a marker of cathepsin K-mediated bone collagen degradation believed to reflect systemic bone resorption, serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP), an index of matrix-metalloprotease (MMP) mediated type I collagen degradation reflecting preferential joint metabolism and urinary CTX-II a biochemical markers of cartilage degradation. Total hip and lumbar spine bone mineral density (BMD) was assessed at baseline, and after 6 and 12 months by DXA.
No patient received bisphosphonates while 77% were under oral glucocorticoids. BMD remained stable over one year. Serum CTX-I levels rapidly decreased by 19% and 28% at week 6 and week 22, respectively (p ANOVA=0.032) values returning to pre-treatment level at week 54. In contrast ICTP levels progressively declined with a maximal 25% decrease at week 54 (p ANOVA=0.028). On the other hand, PINP levels remained stable over time, which led to a 30 to 40% improvement in bone remodeling balance, as assessed by the ratios PINP/CTX and PINP/ICTP (p<0.05). There was no significant change of urinary CTX-II in the whole population, but a slight decrease (P ANOVA=0.041) in those with pretreatment levels above the upper limit of normal range. In summary, the improvement in the formation/resorption marker ratio suggests beneficial systemic and local bone effects of infliximab in patients with RA.
- bone biomarkers
- cartilage biomarkers
- rheumatoid arthritis