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 bone mineral density (BMD) but also by deterioration in bone structure. Anti-IL-6 receptor antibody is used as RA treatment, however its effect on bone strength is not clear. The purpose of this study is to clarify the influence of IL-6 on the changes of bone strength in arthritis, using a mouse model of collagen-induced arthritis (CIA). Additionally, we analyzed what correlates with bone strength in CIA mice.

Methods: CIA was immunized in DBA/1J mice by an intradermal injection of bovine type II collagen on Days 0 and 21. Mice were injected intraperitoneally with anti-mouse IL-6 receptor antibody (MR16-1) on Days 0 and 21. Urine and serum were sampled on Day 33-35. Urinary collagen type 1 cross-linked C-telopeptide (CTX), a bone resorption marker, and serum procollagen type 1 N-terminal propeptide (P1NP), a bone formation marker, were measured by ELISA. Femurs and feet were excised on Day 35, the peak of swelling of joints. As the bone structure, trabecular bone volume (BV/TV) of distal femur, and cortical bone thickness (Ct) of femur shaft, BMD of femur shaft and foot were analysed by micro-computed tomography (μCT). The bone strength of femur shaft was measured a maximum load by bending test.

Results: In CIA mice, urinary CTX and serum P1NP were significantly higher and lower, respectively, than in non-immunized mice. All parameters of bone structure (BV/TV of the distal femur, Ct of the femur shaft, BMD of the femur shaft and the foot) in CIA mice significantly decreased than in non-immunized mice. Moreover, maximum load of the femur shaft in CIA mice was significantly lower than in non-immunized mice. Maximum load of the femur shaft more strongly correlated with Ct of the femur shaft than BMD of the femur shaft and swelling score in hind limb. On the other hand, swelling score in the hind limb most strongly correlated with BMD of the foot, but did not correlate with Ct of the femur shaft. MR16-1 suppressed the development of arthritis. An increase in urinary CTX and a decrease in serum P1NP during development of CIA were suppressed by MR16-1. MR16-1 treatment significantly prevented a decrease in BV/TV of the distal femur, BMD of the foot and maximum load of the femur shaft by CIA induction.

Conclusion: We demonstrated that CIA induced loss of bone strength through a deterioration of bone structure and that cortical thickness has possibility of playing the most important role in bone strength. Moreover, our results indicated that IL-6 played an important role in bone strength because anti-IL-6 receptor antibody prevented the loss in bone strength in CIA.

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