Abstract Background Aseptic loosening and osteolysis are the most common indications after TKA for revision surgery. This meta-analysis which included high-quality randomized controlled trials (RCTs) aimed to analyze the effect of bisphosphonates (BPs) on maintaining periprosthetic bone mineral density (BMD) after total knee arthroplasty. Methods PubMed, AMED, EMBASE, the Cochrane library, ISI Web of Science, and China National Knowledge Infrastructure were systematically searched, five RCTs were included and the total number of participants was 188. The weighted mean differences with 95% confidence interval were calculated to evaluate the efficacy of BPs on total BMD of knee and the BMD of different periprosthetic regions. A descriptive review was performed for BP-related adverse effects. Results The BPs group presented significantly higher total BMD in proximal part of the tibia than the control group at 3 and 6 months (P