Early Anterior Cruciate Ligament Reconstruction Mitigates the Development of Posttraumatic Osteoarthritis in a Murine Anterior Cruciate Ligament Rupture Model.
Academic Article
Overview
abstract
BACKGROUND: Up to 60% of patients develop posttraumatic osteoarthritis (PTOA) 10 to 25 years after anterior cruciate ligament reconstruction (ACLR). While some studies suggest that early ACLR may mitigate PTOA, other studies, by contrast, have found no difference in the timing of ACLR on the development of PTOA. Therefore, the optimal timing of ACLR for the mitigation of PTOA has yet to be fully elucidated in the literature. PURPOSE: To evaluate the effect of timing of ACLR on the development of PTOA using a murine noninvasive (closed) anterior cruciate ligament (ACL) rupture model, as well as on pain-related gait behaviors, peripheral and central immune and inflammatory response, knee range of motion (ROM), and proximal tibial epiphyseal and distal femoral epiphyseal bone volume. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 55 male C57BL/6 mice, 11 to 12 weeks of age, were randomized to 1 of 3 conditions: ACL rupture only, ACL rupture followed by immediate ACLR, or ACL rupture followed by delayed ACLR (7 days after injury). Normal, uninjured animals served as controls. Mice in the immediate and delayed ACLR groups were sacrificed at 28 days postoperatively, and those in the ACL rupture group were sacrificed at 28 days postinjury. The primary outcome measure was histological evaluation using the Osteoarthritis Research Society International (OARSI) score. The secondary outcomes included ROM testing, flow cytometry (from ipsilateral iliac lymph node [iLN] and spleen), gait analysis, and micro-computed tomography (µCT) analysis. RESULTS: The ACL rupture and delayed ACLR groups had higher femoral OARSI scores, consistent with a greater degree of osteoarthritic changes, compared with the control (P < .0001 and P < .0001, respectively) and immediate ACLR (P < .001 and P < .0001, respectively) groups. In addition, the ACL rupture and delayed ACLR groups had higher tibial OARSI scores compared with the control (P < .0001 and P < .001, respectively) and immediate ACLR (P < .01 and P < .01, respectively) groups. There were no differences between groups with respect to ROM or pain-related gait behaviors. There was an increase in total ipsilateral iLN cellularity in the surgical cohorts compared with the ACL rupture and control cohorts. The delayed ACLR group had decreased bone volume in both the proximal tibial epiphysis and distal femoral epiphysis on µCT imaging compared with the immediate ACLR group (P < .001 and P < .01, respectively). CONCLUSION: The authors found that immediate ACLR mitigates the development of PTOA in a murine closed ACL rupture model. CLINICAL RELEVANCE: PTOA is common after ACL injury and surgery. The authors found that early ACLR mitigates PTOA in a murine noninvasive ACL rupture model.
