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Bisphosphonate use and risk of post-operative fracture among patients undergoing a total knee replacement for knee osteoarthritis: a propensity score analysis

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Abstract

Summary

We have shown that patients with osteoarthritis are at increased risk of fracture after total knee replacement (TKR). We conducted a population-based cohort study to assess the effect of bisphosphonate use on their post-surgery fracture risk. Cox regression adjusted by propensity score suggested a 50–55% reduction in risk of fracture post-surgery.

Introduction

Patients with osteoarthritis have a higher bone mass but similar or higher risk of fracture. We recently demonstrated that patients have an elevated fracture risk after TKR, but it is unknown if bisphosphonate therapy in this patient group would reduce fracture risk. We aimed to assess the effect of bisphosphonate prescription to patients undergoing a TKR, on their risk of fracture after surgery.

Methods

From the General Practice Research Database, all patients ≥ 40 years old, who received a TKR from 1986 to 2006 for knee osteoarthritis were eligible. We identified bisphosphonate use (BPU) as the main exposure. Propensity scores (equivalent to the estimated conditional probability of being treated given the individual's covariates) were calculated using logistic regression and used to reduce observed confounding. We fitted Cox models to study the effect of BPU on post-surgery fracture occurrence. Analyses were stratified by history of previous fracture: no fracture, osteoporotic fracture (hip, wrist, humerus, spine), and other fractures.

Results

The hazard ratio (HR) associated with BPU in non-previously fractured patients was 0.50 (95% confidence interval, 0.37–0.68; propensity-adjusted model), and 0.48 (0.35–0.65; matched analysis). In subjects with osteoporotic and with other previous fracture, BPU was associated with a propensity-adjusted HR of 0.46 (0.30 to 0.71) and 0.47 (0.26–0.85), respectively, and with a propensity-matched HR of 0.45 (0.29 to 0.70) and 0.45 (0.25–0.82).

Conclusion

Our results suggest that BPU in primary prevention could reduce post-operative risk of fracture by 50% and by 55% in secondary prevention.

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Acknowledgements

Funding sources

This study was funded by the NIHR Programme Grant for Applied Research Funding Scheme. This work represents the views and opinions of the authors and does not necessarily reflect those of the DH/NIHR. Support was also received from the NIHR Biomedical Research Unit into Musculoskeletal Disease, Nuffield Orthopaedic Centre and University of Oxford.

Partial fundings by: Institut Catala de la Salut-IDIAP Jordi Gol (Grant for a research fellowship, 4th Edition), Instituto de Salud Carlos III, Government of Spain (BAE Grant 2009, Exp.Number BA09/90023), MSD, Novartis and Southampton Rheumatology Trust.

Conflicts of interest

DPA has no conflicts of interest to declare. MKJ, NKA and CC have received honorarium, ad boards and consortium research grants respectively from: Novartis, Alliance for Better Health and Lilly; Merck, MSD, Roche, Novartis, Smith and Nephew, Q-MED, Nicox, Servier, GSK, Schering-Plough, Pfizer and Rottapharm; Alliance for Better Bone Health, Amgen, Novartis, MSD, Servier, Eli Lilly and GSK. The rest of authors have no conflicts of interest to state.

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Authors and Affiliations

  1. NIHR Oxford Musculoskeletal Biomedical Research Unit, University of Oxford, Windmill Road, Headington, Oxford, OX3 7LD, UK

    D. Prieto-Alhambra, M. K. Javaid, A. Judge, J. Maskell, A. Kiran, C. Cooper & N. K. Arden

  2. Institut Catala de la Salut, Barcelona, Spain

    D. Prieto-Alhambra

  3. Internal Medicine Department, Universitat Autonoma de Barcelona, Barcelona, Spain

    D. Prieto-Alhambra

  4. IDIAP Jordi Gol (Primary Care Research Institute), Barcelona, Spain

    D. Prieto-Alhambra

  5. MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK

    J. Maskell, C. Cooper & N. K. Arden

  6. The Botnar Research Centre Institute of Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre, Windmill Road, Oxford, OX3 7LD, UK

    N. K. Arden

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  1. D. Prieto-Alhambra
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Corresponding author

Correspondence to N. K. Arden.

Appendices

Appendix 1

Table 4 READ/OXMIS codes used for the ascertainment of primary total knee replacement
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Appendix 2

Table 5 READ/OXMIS codes used for the ascertainment of fractures
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Appendix 3

Table 6 Fracture occurrence among different bisphophonate users
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Prieto-Alhambra, D., Javaid, M.K., Judge, A. et al. Bisphosphonate use and risk of post-operative fracture among patients undergoing a total knee replacement for knee osteoarthritis: a propensity score analysis. Osteoporos Int 22, 1555–1571 (2011). https://doi.org/10.1007/s00198-010-1368-1

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