Raloxifene Is Associated with Total Knee Arthroplasty in Postmenopausal Women: A Comparative Cohort Study

Post-traumatic osteoarthritis (PTOA) is a distinct form of knee osteoarthritis characterized by accelerated joint degeneration following injury. It poses unique challenges in post-menopausal women due to hormonal changes and altered bone metabolism that create complex pathophysiological environments. This retrospective cohort study compared the effectiveness of different anti-osteoporotic medications in preventing total knee replacement (TKR) in 6155 postmenopausal women with PTOA treated between 2011 and 2021. We compared raloxifene and denosumab, with alendronate serving as the reference group. The primary outcome was TKR occurrence. Cox proportional hazards regression and inverse probability of treatment weighting (IPTW) were performed to estimate hazard ratios, with Kaplan-Meier survival analysis for time-to-event assessment. Participants' mean (SD) age was 69.4 (10.0) years. Given the retrospective nature and typical delayed presentation of PTOA symptoms, cohort entry was defined as the concurrent diagnosis of PTOA and osteoporosis requiring anti-resorptive therapy. Over a mean follow-up of 5.47 years, 26 patients (0.42%) underwent TKR. Raloxifene was associated with a significantly reduced TKR risk compared to alendronate (IPTW-HR 0.81, 95% CI 0.67-0.99, <i>p</i> = 0.040), representing a 19% relative risk reduction. Kaplan-Meier analysis demonstrated raloxifene maintained the lowest cumulative TKR incidence compared to alendronate and denosumab over time, particularly beyond 5 years. These findings suggest that raloxifene may offer superior joint protection compared with alendronate and denosumab in postmenopausal women with PTOA, supporting its potential as a disease-modifying therapeutic option for this vulnerable population.