Oral bisphosphonate use and total knee/hip implant survival:validation of results in an external population-based cohort

OBJECTIVE: Aseptic loosening is the most common cause of revision arthroplasty. Bisphosphonates could minimize this through their antiresorptive effects. This study was undertaken to investigate the association between bisphosphonate use and implant survival.METHODS: A retrospective cohort study was conducted within the Danish nationwide registries (5.5 million residents). Using procedure codes of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, we identified patients age ≥40 years undergoing total joint replacement in 1998-2007. We excluded users of disease-modifying antirheumatic drugs as well as patients with rheumatoid arthritis, Paget's disease, or hip fracture. Participants were classified as bisphosphonate users if they had been receiving treatment for ≥6 months. A time-varying exposure was used to avoid immortal time bias. Up to 6 bisphosphonate nonusers undergoing arthroplasty were matched to each bisphosphonate user, using propensity scores. Stratified Cox regression was performed to model implant survival according to bisphosphonate use. Further, we studied the associations of implant survival with duration of use, adherence (medication possession ratio), and timing of therapy initiation (preoperative/postoperative).RESULTS: Of 95,392 patients with a primary total joint replacement, 80,342 (84.2%) were eligible. We identified 1,590 bisphosphonate users (2.0%), and 1,558 of them (98.0%) were matched to 8,966 bisphosphonate nonusers. Twenty-seven of the 1,558 bisphosphonate users (1.73%) and 399 of the 8,966 matched nonusers (4.45%) underwent revision surgery during the study followup period (at a median 2.61 years after the first surgery [interquartile range 1.04-5.41 years]). Cox regression showed a reduced risk of revision surgery in bisphosphonate users (hazard ratio 0.41 [95% confidence interval 0.27-0.61]). This association was strongest in patients with the longest duration of treatment and/or the best adherence.CONCLUSION: Oral bisphosphonate users have a 59% reduced risk of revision surgery. This association is only present when bisphosphonates are started after arthroplasty surgery. Confirmation in randomized controlled trials is urgently needed.