Antiresorptive Therapy and Revision Risk After Primary Total Knee Arthroplasty: A Systematic Review and Meta-Analysis

Abstract Background This systematic review evaluates whether the use of bisphosphonates or denosumab influences the rate of revision and aseptic loosening after primary total knee arthroplasty (TKA). Additionally, the effects of antiresorptive therapy on periprosthetic fracture risk, bone mineral density (BMD) loss, and migration after TKA were evaluated, along with the potential adverse effects associated with these therapies. Methods A systematic review and meta-analysis were conducted using PubMed, Cochrane Library databases, and gray literature between January 2009 and July 2025 to identify studies evaluating bisphosphonate or denosumab use after primary TKA. Results After screening 253 results, 12 studies encompassing 426,920 patients met the inclusion criteria, with 4 studies eligible for meta-analysis. There were 7 randomized controlled trials) and 5 prospective/retrospective cohort studies; meta-analytic estimates were derived exclusively from registry-based cohorts. Bisphosphonate use was associated with a significantly lower rate of all-cause revision (1.37% vs 2.71%; P = .0046, confidence interval: 0.255-0.779, odds ratio=0.446), although heterogeneity was substantial (P < .0001, I² = 95.5%). No significant protective effect was observed for aseptic loosening, periprosthetic fracture, or BMD beyond 12 months. In assessments of component maximum total point motion, denosumab demonstrated reduced early implant migration (P = .01 and P = .048), with no survivorship outcomes reported. Conclusions Bisphosphonate therapy after TKA is associated with a lower risk of all-cause revision; however, the certainty of evidence is low, and the findings are limited by substantial heterogeneity. No consistent benefit was observed for aseptic loosening, periprosthetic fracture, or long-term BMD preservation.