Background/Purpose: Rheumatoid arthritis (RA) is a disease that typically induces secondary osteoporosis, which increases the risk of bone fractures and, consequently, mortality. Bone fracture is induced not only by lower BMD but also by deterioration in bone structure. It is not clear whether anti–human IL-6 receptor antibody (tocilizumab) affects bone structure in RA patients, and the purpose of this study is to examine the changes in bone structure that occur when arthritis develops and the effects of anti-IL-6 receptor antibody on those changes, using a mouse model of collagen-induced arthritis (CIA).

Methods: CIA was triggered in DBA/1J mice by an intradermal injection of bovine type II collagen on Days 0 and 21. Mice were injected intraperitoneally either with anti-mouse IL-6 receptor antibody (MR16-1) on Days 0 and 21 or with TNF receptor-Fc (TNFR-Fc) 3 times per week from Day 0 to Day 56. Urine and serum were sampled on Day 35, the peak of swelling. Urinary CTX, a bone resorption marker, and serum P1NP, a bone formation marker, were measured by ELISA. Femurs and lumbar spine were excised on Day 56, after swelling subsided. In the distal femur and L5 lumbar spine, the bone structure of trabecular bone and cortical bone was analysed by micro-computed tomography (μCT).

Results: In CIA mice, urinary CTX and serum P1NP were significantly higher and lower, respectively, than in non-immunized mice. Trabecular bone volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th), and cortical bone thickness (Ct) of the distal femur, and BV/TV and Tb. N of the L5 lumbar spine in CIA mice were significantly lower than in non-immunized mice. Both MR16-1 and TNFR-Fc suppressed the development of arthritis. An increase in urinary CTX during development of CIA was prevented by MR16-1 and TNFR-Fc. On the other hand, a decrease in serum P1NP was prevented by only MR16-1. MR16-1 treatment significantly suppressed the deterioration in bone structure (BV/TV, Tb. N, Tb. Th, and Ct in the distal femur, and BV/TV and Ct in the L5 lumbar spine). TNFR-Fc treatment significantly suppressed the decrease of BV/TV and Tb. N in the distal femur.

Conclusion: We demonstrated that CIA induced severe deterioration in bone structure through an imbalance of bone turnover that was a result of not only increased bone resorption but also decreased bone formation. Moreover, our results indicated that proinflammatory cytokines such as IL-6 and TNF play an important role in bone structure deterioration. Our findings indicate that anti-IL-6 receptor antibody improves the imbalance in bone turnover by suppressing both the increase in bone resorption and the decrease in bone formation and thus prevents the deterioration in bone structure.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-il-6-receptor-antibody-prevents-deterioration-in-bone-structure-in-a-mouse-model-of-collagen-induced-arthritis/