Effects of Male and Female Sex on the Development of Posttraumatic Osteoarthritis in the Porcine Knee After Anterior Cruciate Ligament Surgery

Abstract

Background: Posttraumatic osteoarthritis (PTOA) is a common sequela of anterior cruciate ligament (ACL) injury, even when surgical treatment is selected. The effect of patient sex on cartilage health after ACL injury and surgical treatment has been less studied. Purpose/Hypothesis: The study objective was to compare the macroscopic cartilage damage that develops after ACL surgery in male and female Yucatan minipigs. It was hypothesized that after ACL surgery, the macroscopic cartilage damage of the tibiofemoral joints from female animals would be greater than that from male animals. Additionally, it was hypothesized that the effect of sex on the macroscopic cartilage damage would depend on surgical treatment. Study Design: Controlled laboratory study Methods: Twelve-month follow-up data were obtained for 55 adolescent Yucatan minipigs (22 female/33 male) that were randomized to 1 of 3 experimental groups: no treatment (ACL transection [ACLT]), ACL reconstruction, and bridge-enhanced ACL restoration. The Osteoarthritis Research Society International guidelines were used to determine a standardized macroscopic cartilage damage score on 5 surfaces of the knee joint. Results: Females had significantly worse mean total macroscopic cartilage damage scores on the surgical side (adjusted P value [P adj] = .04) and significantly better scores on the contralateral side (P adj = .01) when compared with males. The trochlear damage scores were also significantly worse in females for surgical limbs (P adj = .009) and significantly better for the contralateral limbs (P adj < .001) when compared with males. Although there were no significant differences in total macroscopic cartilage damage scores between sexes within treatment groups on the surgical limbs (ACLT, P adj = 0.45; ACL reconstruction, P adj = .56; bridge-enhanced ACL restoration, P adj = .23), the mean trochlear scores on the surgical limb of females were significantly worse than those of the males in the ACLT group (P adj = .003). Conclusion: Mean total macroscopic cartilage damage scores of Yucatan minipigs were significantly worse in females than males, regardless of treatment. These differences were predominantly found in the trochlear scores across all treatment groups. Clinical Relevance: These data suggest that patient sex could be more influential in the progression of PTOA than surgical treatment after ACL injury. Identifying factors responsible for this discrepancy may prove valuable to identify targets to slow PTOA progression in male and female ACL-injured populations.