Background/Purpose: Osteoporotic patients with no evidence of fractures sometimes experience vague low back pain. Bone pain associated with bone metastasis may also be related to increased osteoclastic bone resorption suggesting that osteoporosis-related bone pain is caused by increased osteoclastic bone resorption. J.Mysliwiec et al suggested that Interleukin-6 (IL-6) plays a considerable role of in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in estrogen-deficient women. In prospective study, IL-6 receptor inhibitor (IL-6Ri) increased the BMD of RA patients who had osteopenia. In addition, anti-IL-6R antibody inhibits systemic bone loss in the collagen-induced arthritis model mice. In this study, we investigated the effect of anti-IL-6R antibody on pain-related behavior and bone morphometry in ovariectomized mice.

Methods: 8-week-old female ddY mice were ovariectomized (OVX) and assigned to 3groups; SHAM-operated mice treated with vehicle (SHAM), OVX mice treated with vehicle (OVX), OVX mice treated with anti-IL-6R antibody  (IL-6Ri). Starting immediately after surgery, vehicle or 2mg anti-IL-6R antibody was injected subcutaneously once a week for 4 weeks. The bilateral proximal tibial metaphyses were analyzed three-dimensionally by μCT 4 weeks after surgery (each group; 8 mice). Mechanical sensitivity was tested using von Frey filaments 4 weeks after surgery. The frequency of the withdrawal response and the withdrawal threshold to the application of von Frey filaments to the planter surface of the hindpaws was examined. To evaluate the frequency of the withdrawal response, three von Frey filaments with forces of 0.4, 0.6 and 1.4 were applied 5 times each in ascending order of force, and the number and intensity of withdrawal responses were noted. Results were expressed as the percent response frequency of paw withdrawals. To evaluate the withdrawal threshold, each von Frey filament was applied once, starting with 0.008g and increasing until a withdrawal response was reached, which was considered a positive response. The lowest force producing a response was considered the withdrawal threshold.

Results:μCT analysis of the femoral distal metaphysis and the proximal tibial metaphysis showed that bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) were significantly less in the OVX group than in the SHAM group, whereas trabecular separation (Tb.Sp) was significantly greater in the OVX group than in the SHAM group. IL-6Ri treatment was no effect on bone morphometry compared with OVX group. The withdrawal threshold was significantly lower in the OVX group than in the SHAM group, and was significantly improved in the IL-6Ri group than in the OVX group. The paw-withdrawal-frequency stimulated by von Frey filaments with strength of 0.4, 0.6 and 1.4 g was significantly higher in the OVX group than in the SHAM group, and von Frey filaments with strength of 1.4g was significantly higher in the OVX group than in the IL-6Ri group. Anti-IL-6R antibody improved mechanical hyperalgesia in hindlimbs. 

Conclusion: In this study, anti-IL-6R antibody prevented mechanical hyperalgesia in hindlimbs in hindlims of OVX mice, but did not prevent ovariectomy-induced bone loss.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-anti-interleukin-6-receptor-antibody-in-ovariectomized-mice/