High‐fat diet exacerbates pain‐like behaviors and periarticular bone loss in mice with CFA‐induced knee arthritis

Objective Our aim was to quantify nociceptive spontaneous behaviors, knee edema, proinflammatory cytokines, bone density, and microarchitecture in high‐fat diet (HFD)‐fed mice with unilateral knee arthritis. Methods ICR male mice were fed either standard diet (SD) or HFD starting at 3 weeks old. At 17 weeks, HFD and SD mice received intra‐articular injections either with Complete Freund's Adjuvant (CFA) or saline into the right knee joint every 7 days for 4 weeks. Spontaneous pain‐like behaviors and knee edema were assessed for 26 days. At day 26 post‐first CFA injection, serum levels of IL‐1β, IL‐6, and RANKL were measured by ELISA, and microcomputed tomography analysis of knee joints was performed. Results HFD‐fed mice injected with CFA showed greater spontaneous pain‐like behaviors of the affected extremity as well as a decrease in the weight‐bearing index compared to SD‐fed mice injected with CFA. Knee edema was not significantly different between diets. HFD significantly exacerbated arthritis‐induced bone loss at the distal femoral metaphysis but had no effect on femoral diaphyseal cortical bone. HFD did not modify serum levels of proinflammatory cytokines. Conclusions HFD exacerbates pain‐like behaviors and significantly increases the magnitude of periarticular trabecular bone loss in a murine model of unilateral arthritis.