Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease that is initiated by a traumatic joint injury. Current treatments during the early phase (<7 days) post-injury aim to reduce pain and inflammation through rest (unloading) and non-steroidal anti-inflammatory drug (NSAID) treatment, but how those early phase interventions impact long-term PTOA progression is unknown. We hypothesized that early unloading and NSAID treatment would both diminish joint inflammation and slow PTOA progression
In this study, we use a noninvasive anterior cruciate ligament rupture (ACL-R) mouse model to investigate whether PTOA progression can be slowed with early phase hindlimb unloading (HLU) and/or daily celecoxib (CXB) treatment following ACL-R. Inflammatory protease activity was evaluated using in vivo fluorescence imaging, osteophyte formation and epiphyseal trabecular bone microstructure were quantified using micro-computed tomography, and synovitis and PTOA progression were examined using whole-joint histology at 0, 7, 14, 21, and 28 days post-injury
Hindlimb unloading significantly reduced protease activity and synovitis in injured joints during the unloading period, but these returned to control levels during subsequent reloading. Similarly, trabecular bone volume was partially preserved in injured limbs with HLU, but returned to control values with reloading. Mineralized osteophyte volume was significantly reduced at 21 and 28 days post-injury by both HLU and CXB, but there was not a synergistic effect of these treatments. Similarly, HLU delayed PTOA progression in injured knee joints.
These data suggest that early unloading following a joint injury can diminish inflammation and can potentially have long-term benefits for joint health.