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Published in: Osteoporosis International 5/2011

01-05-2011 | Original Article

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

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

Published in: Osteoporosis International | Issue 5/2011

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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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Literature
1.
go back to reference Cooper C, Campion G, Melton LJ 3rd (1992) Hip fractures in the elderly: a world-wide projection. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2:285–289 Cooper C, Campion G, Melton LJ 3rd (1992) Hip fractures in the elderly: a world-wide projection. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2:285–289
2.
go back to reference Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF (1987) The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum 30:914–918PubMedCrossRef Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF (1987) The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum 30:914–918PubMedCrossRef
3.
go back to reference Jordan KM, Sawyer S, Coakley P, Smith HE, Cooper C, Arden NK (2004) The use of conventional and complementary treatments for knee osteoarthritis in the community. Rheumatology (Oxford, England) 43:381–384CrossRef Jordan KM, Sawyer S, Coakley P, Smith HE, Cooper C, Arden NK (2004) The use of conventional and complementary treatments for knee osteoarthritis in the community. Rheumatology (Oxford, England) 43:381–384CrossRef
4.
go back to reference National Joint R (2009) National Joint Registry for England and Wales. 6th Annual Report National Joint R (2009) National Joint Registry for England and Wales. 6th Annual Report
5.
go back to reference Laupacis A, Bourne R, Rorabeck C, Feeny D, Wong C, Tugwell P, Leslie K, Bullas R (1994) Costs of elective total hip arthroplasty during the first year. Cemented versus noncemented. J Arthroplasty 9:481–487PubMedCrossRef Laupacis A, Bourne R, Rorabeck C, Feeny D, Wong C, Tugwell P, Leslie K, Bullas R (1994) Costs of elective total hip arthroplasty during the first year. Cemented versus noncemented. J Arthroplasty 9:481–487PubMedCrossRef
6.
go back to reference Foss MV, Byers PD (1972) Bone density, osteoarthrosis of the hip, and fracture of the upper end of the femur. Ann Rheum Dis 31:259–264PubMedCrossRef Foss MV, Byers PD (1972) Bone density, osteoarthrosis of the hip, and fracture of the upper end of the femur. Ann Rheum Dis 31:259–264PubMedCrossRef
7.
go back to reference Nevitt MC, Lane NE, Scott JC, Hochberg MC, Pressman AR, Genant HK, Cummings SR (1995) Radiographic osteoarthritis of the hip and bone mineral density. The Study of Osteoporotic Fractures Research Group. Arthritis Rheum 38:907–916PubMedCrossRef Nevitt MC, Lane NE, Scott JC, Hochberg MC, Pressman AR, Genant HK, Cummings SR (1995) Radiographic osteoarthritis of the hip and bone mineral density. The Study of Osteoporotic Fractures Research Group. Arthritis Rheum 38:907–916PubMedCrossRef
8.
go back to reference Hannan MT, Anderson JJ, Zhang Y, Levy D, Felson DT (1993) Bone mineral density and knee osteoarthritis in elderly men and women. The Framingham Study. Arthritis Rheum 36:1671–1680PubMedCrossRef Hannan MT, Anderson JJ, Zhang Y, Levy D, Felson DT (1993) Bone mineral density and knee osteoarthritis in elderly men and women. The Framingham Study. Arthritis Rheum 36:1671–1680PubMedCrossRef
9.
go back to reference Abdin-Mohamed M, Jameson K, Dennison EM, Cooper C, Arden NK, Hertfordshire Cohort Study G (2009) Volumetric bone mineral density of the tibia is not increased in subjects with radiographic knee osteoarthritis. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society 17:174–177PubMedCrossRef Abdin-Mohamed M, Jameson K, Dennison EM, Cooper C, Arden NK, Hertfordshire Cohort Study G (2009) Volumetric bone mineral density of the tibia is not increased in subjects with radiographic knee osteoarthritis. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society 17:174–177PubMedCrossRef
10.
go back to reference Arden NK, Griffiths GO, Hart DJ, Doyle DV, Spector TD (1996) The association between osteoarthritis and osteoporotic fracture: the Chingford Study. Br J Rheumatol 35:1299–1304PubMedCrossRef Arden NK, Griffiths GO, Hart DJ, Doyle DV, Spector TD (1996) The association between osteoarthritis and osteoporotic fracture: the Chingford Study. Br J Rheumatol 35:1299–1304PubMedCrossRef
11.
go back to reference Bergink AP, van der Klift M, Hofman A, Verhaar JA, van Leeuwen JP, Uitterlinden AG, Pols HA (2003) Osteoarthritis of the knee is associated with vertebral and nonvertebral fractures in the elderly: the Rotterdam Study. Arthritis Rheum 49:648–657PubMedCrossRef Bergink AP, van der Klift M, Hofman A, Verhaar JA, van Leeuwen JP, Uitterlinden AG, Pols HA (2003) Osteoarthritis of the knee is associated with vertebral and nonvertebral fractures in the elderly: the Rotterdam Study. Arthritis Rheum 49:648–657PubMedCrossRef
12.
go back to reference Arden NK, Crozier S, Smith H, Anderson F, Edwards C, Raphael H, Cooper C (2006) Knee pain, knee osteoarthritis, and the risk of fracture. Arthritis Rheum 55:610–615PubMedCrossRef Arden NK, Crozier S, Smith H, Anderson F, Edwards C, Raphael H, Cooper C (2006) Knee pain, knee osteoarthritis, and the risk of fracture. Arthritis Rheum 55:610–615PubMedCrossRef
13.
go back to reference Prieto-Alhambra D, Javaid M, Maskell J, Judge A, Nevitt M, Cooper C, Arden NK (2010) Changes in Hip Fracture Rate before and after total knee replacement due to Osteoarthritis: a population-based cohort study. Ann Rheum Dis (in press) Prieto-Alhambra D, Javaid M, Maskell J, Judge A, Nevitt M, Cooper C, Arden NK (2010) Changes in Hip Fracture Rate before and after total knee replacement due to Osteoarthritis: a population-based cohort study. Ann Rheum Dis (in press)
14.
go back to reference Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR (2000) Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124PubMedCrossRef Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR (2000) Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124PubMedCrossRef
15.
go back to reference Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282:1344–1352PubMedCrossRef Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282:1344–1352PubMedCrossRef
16.
go back to reference Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:637–645PubMedCrossRef Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:637–645PubMedCrossRef
17.
go back to reference Seeman E (2006) Strontium ranelate: vertebral and non-vertebral fracture risk reduction. Curr Opin Rheumatol 18(Suppl 1):S17–S20PubMedCrossRef Seeman E (2006) Strontium ranelate: vertebral and non-vertebral fracture risk reduction. Curr Opin Rheumatol 18(Suppl 1):S17–S20PubMedCrossRef
18.
go back to reference Spector TD (2003) Bisphosphonates: potential therapeutic agents for disease modification in osteoarthritis. Aging Clin Exp Res 15:413–418PubMed Spector TD (2003) Bisphosphonates: potential therapeutic agents for disease modification in osteoarthritis. Aging Clin Exp Res 15:413–418PubMed
19.
go back to reference Bingham CO 3rd, Buckland-Wright JC, Garnero P, Cohen SB, Dougados M, Adami S, Clauw DJ, Spector TD, Pelletier JP, Raynauld JP, Strand V, Simon LS, Meyer JM, Cline GA, Beary JF (2006) Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum 54:3494–3507PubMedCrossRef Bingham CO 3rd, Buckland-Wright JC, Garnero P, Cohen SB, Dougados M, Adami S, Clauw DJ, Spector TD, Pelletier JP, Raynauld JP, Strand V, Simon LS, Meyer JM, Cline GA, Beary JF (2006) Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum 54:3494–3507PubMedCrossRef
20.
21.
go back to reference Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397PubMedCrossRef Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397PubMedCrossRef
22.
go back to reference Kanis JA, Group WHOS (2007) Assessment of osteoporosis at the primary health care level. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield 2007 (available on request from the WHO Collaborating Centre or the IOF) Kanis JA, Group WHOS (2007) Assessment of osteoporosis at the primary health care level. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield 2007 (available on request from the WHO Collaborating Centre or the IOF)
23.
go back to reference Van Staa TP, Abenhaim L, Cooper C, Zhang B, Leufkens HG (2000) The use of a large pharmacoepidemiological database to study exposure to oral corticosteroids and risk of fractures: validation of study population and results. Pharmacoepidemiol Drug Saf 9:359–366PubMedCrossRef Van Staa TP, Abenhaim L, Cooper C, Zhang B, Leufkens HG (2000) The use of a large pharmacoepidemiological database to study exposure to oral corticosteroids and risk of fractures: validation of study population and results. Pharmacoepidemiol Drug Saf 9:359–366PubMedCrossRef
24.
go back to reference Brankin E, Walker M, Lynch N, Aspray T, Lis Y, Cowell W (2006) The impact of dosing frequency on compliance and persistence with bisphosphonates among postmenopausal women in the UK: evidence from three databases. Curr Med Res Opin 22:1249–1256PubMedCrossRef Brankin E, Walker M, Lynch N, Aspray T, Lis Y, Cowell W (2006) The impact of dosing frequency on compliance and persistence with bisphosphonates among postmenopausal women in the UK: evidence from three databases. Curr Med Res Opin 22:1249–1256PubMedCrossRef
25.
go back to reference Rosenbaum PR, Rubin DB (1983) The central role of the propensity score in observational studies for causal effects. Biometrika 70:15CrossRef Rosenbaum PR, Rubin DB (1983) The central role of the propensity score in observational studies for causal effects. Biometrika 70:15CrossRef
26.
go back to reference Braitman LE, Rosenbaum PR (2002) Rare outcomes, common treatments: analytic strategies using propensity scores. Ann Intern Med 137:693–695PubMed Braitman LE, Rosenbaum PR (2002) Rare outcomes, common treatments: analytic strategies using propensity scores. Ann Intern Med 137:693–695PubMed
27.
go back to reference Normand SL, Sykora K, Li P, Mamdani M, Rochon PA, Anderson GM (2005) Readers guide to critical appraisal of cohort studies: 3. Analytical strategies to reduce confounding. BMJ 330:1021–1023PubMedCrossRef Normand SL, Sykora K, Li P, Mamdani M, Rochon PA, Anderson GM (2005) Readers guide to critical appraisal of cohort studies: 3. Analytical strategies to reduce confounding. BMJ 330:1021–1023PubMedCrossRef
28.
go back to reference Austin PC (2009) Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations. Biom J 51:171–184PubMedCrossRef Austin PC (2009) Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations. Biom J 51:171–184PubMedCrossRef
29.
go back to reference Barratt A, Wyer PC, Hatala R, McGinn T, Dans AL, Keitz S, Moyer V, For GG (2004) Tips for learners of evidence-based medicine: 1. Relative risk reduction, absolute risk reduction and number needed to treat. CMAJ 171:353–358PubMedCrossRef Barratt A, Wyer PC, Hatala R, McGinn T, Dans AL, Keitz S, Moyer V, For GG (2004) Tips for learners of evidence-based medicine: 1. Relative risk reduction, absolute risk reduction and number needed to treat. CMAJ 171:353–358PubMedCrossRef
30.
go back to reference Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353:878–882PubMedCrossRef Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353:878–882PubMedCrossRef
31.
go back to reference Spector TD, Conaghan PG, Buckland-Wright JC, Garnero P, Cline GA, Beary JF, Valent DJ, Meyer JM (2005) Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]. Arthritis Res Ther 7:R625–R633PubMedCrossRef Spector TD, Conaghan PG, Buckland-Wright JC, Garnero P, Cline GA, Beary JF, Valent DJ, Meyer JM (2005) Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]. Arthritis Res Ther 7:R625–R633PubMedCrossRef
32.
go back to reference Carbone LD, Nevitt MC, Wildy K, Barrow KD, Harris F, Felson D, Peterfy C, Visser M, Harris TB, Wang BW, Kritchevsky SB, Health A, Body Composition S (2004) The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis. Arthritis Rheum 50:3516–3525PubMedCrossRef Carbone LD, Nevitt MC, Wildy K, Barrow KD, Harris F, Felson D, Peterfy C, Visser M, Harris TB, Wang BW, Kritchevsky SB, Health A, Body Composition S (2004) The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis. Arthritis Rheum 50:3516–3525PubMedCrossRef
33.
go back to reference Buckland-Wright JC, Messent EA, Bingham CO 3rd, Ward RJ, Tonkin C (2007) A 2 yr longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients. Rheumatology (Oxford) 46:257–264CrossRef Buckland-Wright JC, Messent EA, Bingham CO 3rd, Ward RJ, Tonkin C (2007) A 2 yr longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients. Rheumatology (Oxford) 46:257–264CrossRef
34.
go back to reference Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR, Fracture Intervention T (2000) Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124PubMedCrossRef Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR, Fracture Intervention T (2000) Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124PubMedCrossRef
35.
go back to reference Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280:2077–2082PubMedCrossRef Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280:2077–2082PubMedCrossRef
36.
go back to reference Sheehy O, Kindundu CM, Barbeau M, LeLorier J (2009) Differences in persistence among different weekly oral bisphosphonate medications. Osteoporos Int 20:1369–1376PubMedCrossRef Sheehy O, Kindundu CM, Barbeau M, LeLorier J (2009) Differences in persistence among different weekly oral bisphosphonate medications. Osteoporos Int 20:1369–1376PubMedCrossRef
37.
go back to reference Caro JJ, Ishak KJ, Huybrechts KF, Raggio G, Naujoks C (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 15:1003–1008 Caro JJ, Ishak KJ, Huybrechts KF, Raggio G, Naujoks C (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 15:1003–1008
38.
go back to reference Austin PC (2008) The performance of different propensity-score methods for estimating relative risks. J Clin Epidemiol 61:537–545PubMedCrossRef Austin PC (2008) The performance of different propensity-score methods for estimating relative risks. J Clin Epidemiol 61:537–545PubMedCrossRef
Metadata
Title
Bisphosphonate use and risk of post-operative fracture among patients undergoing a total knee replacement for knee osteoarthritis: a propensity score analysis
Authors
D. Prieto-Alhambra
M. K. Javaid
A. Judge
J. Maskell
A. Kiran
C. Cooper
N. K. Arden
Publication date
01-05-2011
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 5/2011
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-010-1368-1

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