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Extended report
Effect of bisphosphonates on knee replacement surgery
  1. Tuhina Neogi,
  2. Shanshan Li,
  3. Christine Peloquin,
  4. Devyani Misra,
  5. Yuqing Zhang
  1. Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts, USA
  1. Correspondence to Dr Tuhina Neogi, Boston University School of Medicine, 650 Albany Street, Suite X200, Clin Epi Unit, Boston, MA 02118, USA; tneogi{at}


Purpose Bone remodelling as a therapeutic target in knee osteoarthritis (OA) has gained much interest, but the effects of antiresorptive agents on knee OA have been conflicting, with no studies to date examining the effects of bisphosphonate use on the clinically relevant endpoint of knee replacement (KR) surgery.

Methods We used data from The Health Improvement Network (THIN), a general practitioner electronic medical records representative of the general UK population. We identified older women who had initiated bisphosphonate use after their incident knee OA diagnosis. Each bisphosphonate initiator was propensity score-matched with a non-initiator within each 1-year cohort accrual block. The effect of bisphosphonates on the risk of KR was assessed using Cox proportional hazard regression. Sensitivity analyses to address residual confounding were also conducted.

Results We identified 2006 bisphosphonate initiators, who were matched to 2006 non-initiators(mean age 76, mean body mass index 27), with mean follow-up time of 3 years. The crude incidence rate of KR was 22.0 per 1000 person-years among the initiators, and 29.1 among the non-initiators. Bisphosphonate initiators had 26% lower risk of KR than non-initiators(HR 0.74, 95% CI 0.59 to 0.93); these results were similar when additionally adjusted for potential confounders in the propensity score (HR 0.76, 95% CI 0.60 to 0.95). Results of sensitivity analyses supported this protective effect.

Conclusions In this population-based cohort of older women with incident knee OA, those with incident bisphosphonate users had lower risk of KR than non-users of bisphosphonates, suggesting a potential beneficial effect of bisphosphonates on knee OA.

  • knee osteoarthritis
  • treatment
  • orthopedic surgery

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  • Handling editor Tore K Kvien

  • Contributors All authors: participated in the study design, interpretation of results and manuscript preparation. TN: additionally drafted and revised the manuscript. CP: additionally extracted and analysed the data.

  • Funding NIH (NIAMS) P60AR047885 and K24AR070892, and Arthritis Foundation Innovative Research Grant.

  • Competing interests None declared.

  • Ethics approval Boston University Medical Campus Institutional Review Board (protocol H-32821).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The Health Improvement Network (THIN) dataset is a subscription-based dataset with a legal contract requiring data to remain onsite and be analysed at Boston University Medical Center. We are therefore not legally able to make these data available publicly. We would be happy to collaborate with potential external collaborators to address research questions of interest using THIN if appropriate resources are provided.

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