Arthroplasty Today - 2026-04-01 - Journal Article
Antiresorptive Therapy and Revision Risk After Primary Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.
Huffman AB, Burbelo A, Stone W, Darbandi A, Cleary L, Vadapalli RC, Bullock M
Topics
Key Takeaway
Bisphosphonate use after primary TKA was associated with a 54% reduction in all-cause revision risk (1.37% vs 2.71%; OR 0.446), but evidence certainty is low due to I² = 95.5% heterogeneity.
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Summary
This systematic review and meta-analysis asked whether bisphosphonate or denosumab use after primary TKA reduces revision risk, aseptic loosening, periprosthetic fracture, or implant migration. Across 12 studies (426,920 patients), bisphosphonate use was associated with significantly lower all-cause revision rates (1.37% vs 2.71%; OR 0.446, p=0.0046), but no significant protective effect was found for aseptic loosening, periprosthetic fracture, or BMD preservation beyond 12 months. Denosumab reduced early implant migration by maximum total point motion metrics (p=0.01 and p=0.048), but no survivorship data were reported for this agent.
Key Limitation
The 7 RCTs were excluded from meta-analysis, meaning the quantitative pooled estimate derives entirely from registry cohorts with uncontrolled confounding by indication (patients on bisphosphonates differ systematically from those who are not).
Original 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, I 2 = 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.