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Published in: Osteoporosis International 3/2014

01-03-2014 | Original Article

Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporosis: a systematic review and meta-analysis

Authors: S.-H. Lee, S.-S. Chang, M. Lee, R.-C. Chan, C.-C. Lee

Published in: Osteoporosis International | Issue 3/2014

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Abstract

Summary

We aimed to systematically review observational studies evaluating use of bisphosphonates (BPs) and risk of osteonecrosis of jaw (ONJ) or other sites among non-cancer patients.

Introduction

PubMed, EMBASE, and Cochrane Library were screened from database inception to Dec 2012.

Methods

Two reviewers independently identified cohort and case–control studies evaluating the use of oral or intravenous (IV) BPs and the risk of ONJ and extracted the characteristics of the studies and risk estimates. Pooled estimates of odds ratios and 95 % confidence intervals (CI) were derived by random effects meta-analysis. Subgroup analyses were carried according to patients’ characteristics and route of BP use.

Results

We identified 12 studies, including 2,652 cases and 1,571,997 controls. Use of BPs was associated with a significantly increased risk of ONJ or ON of other sites [odds ratio (OR) 2.32; 95 % CI 1.38–3.91; I 2 = 91 %]. The summary OR was 2.91 (95 % CI 1.62–5.22; I 2 = 85.9 %) for adjusted studies. Use of BPs were associated with higher risk on ONJ (OR 2.57; 95 % CI 1.37–4.84; I 2 = 92.2 %) than ON of other sites (OR 1.79; 95 % CI 0.71–4.47; I 2 = 83.3 %). Meta-regression analysis did not find design characteristics or outcome definitions to be significant sources of heterogeneity.

Conclusion

The available evidence suggests that use of BPs in cancer patients is associated with a substantial risk for ONJ. Patients receiving IV BP are at highest risk.
Literature
1.
go back to reference Rizzoli R, Reginster JY (2011) Adverse drug reactions to osteoporosis treatments. Expert Rev Clin Pharmacol 4(5):593–604PubMedCrossRef Rizzoli R, Reginster JY (2011) Adverse drug reactions to osteoporosis treatments. Expert Rev Clin Pharmacol 4(5):593–604PubMedCrossRef
2.
go back to reference Varun B, Sivakumar T, Nair BJ, Joseph AP (2012) Bisphosphonate induced osteonecrosis of jaw in breast cancer patients: a systematic review. J Oral Maxillofac Pathol 16(2):210–214PubMedCentralPubMedCrossRef Varun B, Sivakumar T, Nair BJ, Joseph AP (2012) Bisphosphonate induced osteonecrosis of jaw in breast cancer patients: a systematic review. J Oral Maxillofac Pathol 16(2):210–214PubMedCentralPubMedCrossRef
3.
go back to reference Yamazaki T, Yamori M, Ishizaki T et al (2012) Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study. Int J Oral Maxillofac Surg 41(11):1397–1403PubMedCrossRef Yamazaki T, Yamori M, Ishizaki T et al (2012) Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study. Int J Oral Maxillofac Surg 41(11):1397–1403PubMedCrossRef
4.
go back to reference Wessel JH, Dodson TB, Zavras AI (2008) Zoledronate, smoking, and obesity are strong risk factors for osteonecrosis of the jaw: a case–control study. J Oral Maxillofac Surg 66(4):625–631PubMedCentralPubMedCrossRef Wessel JH, Dodson TB, Zavras AI (2008) Zoledronate, smoking, and obesity are strong risk factors for osteonecrosis of the jaw: a case–control study. J Oral Maxillofac Surg 66(4):625–631PubMedCentralPubMedCrossRef
5.
go back to reference Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61(9):1115–1117PubMedCrossRef Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61(9):1115–1117PubMedCrossRef
6.
go back to reference Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62(5):527–534PubMedCrossRef Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62(5):527–534PubMedCrossRef
7.
go back to reference Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63(11):1567–1575PubMedCrossRef Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63(11):1567–1575PubMedCrossRef
8.
go back to reference Badros A, Weikel D, Salama A et al (2006) Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 24(6):945–952PubMedCrossRef Badros A, Weikel D, Salama A et al (2006) Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 24(6):945–952PubMedCrossRef
9.
go back to reference Zavras AI, Zhu S (2006) Bisphosphonates are associated with increased risk for jaw surgery in medical claims data: is it osteonecrosis? J Oral Maxillofac Surg 64(6):917–923PubMedCrossRef Zavras AI, Zhu S (2006) Bisphosphonates are associated with increased risk for jaw surgery in medical claims data: is it osteonecrosis? J Oral Maxillofac Surg 64(6):917–923PubMedCrossRef
10.
go back to reference Wilkinson GS, Kuo YF, Freeman JL, Goodwin JS (2007) Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis. J Natl Cancer Inst 99(13):1016–1024PubMedCrossRef Wilkinson GS, Kuo YF, Freeman JL, Goodwin JS (2007) Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis. J Natl Cancer Inst 99(13):1016–1024PubMedCrossRef
11.
go back to reference Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P (2007) A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther 29(8):1548–1558PubMedCrossRef Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P (2007) A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther 29(8):1548–1558PubMedCrossRef
12.
go back to reference Allen MR, Burr DB (2009) The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 67(5 Suppl):61–70PubMedCrossRef Allen MR, Burr DB (2009) The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 67(5 Suppl):61–70PubMedCrossRef
13.
go back to reference Pazianas M, Russell RG, Fogelman I (2009) Osteonecrosis of the jaw: more heat than light. J Nucl Med 50(1):6–7PubMedCrossRef Pazianas M, Russell RG, Fogelman I (2009) Osteonecrosis of the jaw: more heat than light. J Nucl Med 50(1):6–7PubMedCrossRef
14.
go back to reference Garrison LP Jr, Neumann PJ, Erickson P, Marshall D, Mullins CD (2007) Using real-world data for coverage and payment decisions: the ISPOR Real-World Data Task Force report. Value Health 10(5):326–335PubMedCrossRef Garrison LP Jr, Neumann PJ, Erickson P, Marshall D, Mullins CD (2007) Using real-world data for coverage and payment decisions: the ISPOR Real-World Data Task Force report. Value Health 10(5):326–335PubMedCrossRef
15.
go back to reference Motheral BR, Fairman KA (1997) The use of claims databases for outcomes research: rationale, challenges, and strategies. Clin Ther 19(2):346–366PubMedCrossRef Motheral BR, Fairman KA (1997) The use of claims databases for outcomes research: rationale, challenges, and strategies. Clin Ther 19(2):346–366PubMedCrossRef
16.
go back to reference Recker RR, Lewiecki EM, Miller PD, Reiffel J (2009) Safety of bisphosphonates in the treatment of osteoporosis. Am J Med 122(2 Suppl):S22–32PubMedCrossRef Recker RR, Lewiecki EM, Miller PD, Reiffel J (2009) Safety of bisphosphonates in the treatment of osteoporosis. Am J Med 122(2 Suppl):S22–32PubMedCrossRef
17.
go back to reference Etminan M, Aminzadeh K, Matthew IR, Brophy JM (2008) Use of oral bisphosphonates and the risk of aseptic osteonecrosis: a nested case–control study. J Rheumatol 35(4):691–695PubMed Etminan M, Aminzadeh K, Matthew IR, Brophy JM (2008) Use of oral bisphosphonates and the risk of aseptic osteonecrosis: a nested case–control study. J Rheumatol 35(4):691–695PubMed
18.
go back to reference Pazianas M, Blumentals WA, Miller PD (2008) Lack of association between oral bisphosphonates and osteonecrosis using jaw surgery as a surrogate marker. Osteoporos Int 19(6):773–779PubMedCrossRef Pazianas M, Blumentals WA, Miller PD (2008) Lack of association between oral bisphosphonates and osteonecrosis using jaw surgery as a surrogate marker. Osteoporos Int 19(6):773–779PubMedCrossRef
19.
go back to reference Cooper C, Steinbuch M, Stevenson R, Miday R, Watts NB (2010) The epidemiology of osteonecrosis: findings from the GPRD and THIN databases in the UK. Osteoporos Int 21(4):569–577PubMedCentralPubMedCrossRef Cooper C, Steinbuch M, Stevenson R, Miday R, Watts NB (2010) The epidemiology of osteonecrosis: findings from the GPRD and THIN databases in the UK. Osteoporos Int 21(4):569–577PubMedCentralPubMedCrossRef
20.
go back to reference Kallmes DF, Rad AE, Gray LA, McDonald RJ, Clarke BL (2009) Bisphosphonates are not associated with vertebral osteonecrosis. J Bone Miner Metab 27(4):452–455PubMedCrossRef Kallmes DF, Rad AE, Gray LA, McDonald RJ, Clarke BL (2009) Bisphosphonates are not associated with vertebral osteonecrosis. J Bone Miner Metab 27(4):452–455PubMedCrossRef
21.
go back to reference Pavkovic M, Petrushevska G, Jovanovic R et al (2010) Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates. Prilozi 31(2):39–49PubMed Pavkovic M, Petrushevska G, Jovanovic R et al (2010) Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates. Prilozi 31(2):39–49PubMed
22.
go back to reference Fellows JL, Rindal DB, Barasch A et al (2011) ONJ in two dental practice-based research network regions. J Dent Res 90(4):433–438PubMedCrossRef Fellows JL, Rindal DB, Barasch A et al (2011) ONJ in two dental practice-based research network regions. J Dent Res 90(4):433–438PubMedCrossRef
23.
go back to reference Barasch A, Cunha-Cruz J, Curro FA et al (2011) Risk factors for osteonecrosis of the jaws: a case–control study from the CONDOR dental PBRN. J Dent Res 90(4):439–444PubMedCrossRef Barasch A, Cunha-Cruz J, Curro FA et al (2011) Risk factors for osteonecrosis of the jaws: a case–control study from the CONDOR dental PBRN. J Dent Res 90(4):439–444PubMedCrossRef
24.
go back to reference Baillargeon J, Kuo YF, Lin YL, Wilkinson GS, Goodwin JS (2011) Osteonecrosis of the jaw in older osteoporosis patients treated with intravenous bisphosphonates. Ann Pharmacother 45(10):1199–1206PubMedCrossRef Baillargeon J, Kuo YF, Lin YL, Wilkinson GS, Goodwin JS (2011) Osteonecrosis of the jaw in older osteoporosis patients treated with intravenous bisphosphonates. Ann Pharmacother 45(10):1199–1206PubMedCrossRef
25.
go back to reference Tennis P, Rothman KJ, Bohn RL et al (2012) Incidence of osteonecrosis of the jaw among users of bisphosphonates with selected cancers or osteoporosis. Pharmacoepidemiol Drug Saf 21(8):810–817PubMedCrossRef Tennis P, Rothman KJ, Bohn RL et al (2012) Incidence of osteonecrosis of the jaw among users of bisphosphonates with selected cancers or osteoporosis. Pharmacoepidemiol Drug Saf 21(8):810–817PubMedCrossRef
26.
go back to reference Vestergaard P, Schwartz K, Rejnmark L, Mosekilde L, Pinholt EM (2012) Oral bisphosphonate use increases the risk for inflammatory jaw disease: a cohort study. J Oral Maxillofac Surg 70(4):821–829PubMedCrossRef Vestergaard P, Schwartz K, Rejnmark L, Mosekilde L, Pinholt EM (2012) Oral bisphosphonate use increases the risk for inflammatory jaw disease: a cohort study. J Oral Maxillofac Surg 70(4):821–829PubMedCrossRef
27.
go back to reference Lapi F, Cipriani F, Caputi AP et al (2013) Assessing the risk of osteonecrosis of the jaw due to bisphosphonate therapy in the secondary prevention of osteoporotic fractures. Osteoporos Int 24(2):697–705PubMedCrossRef Lapi F, Cipriani F, Caputi AP et al (2013) Assessing the risk of osteonecrosis of the jaw due to bisphosphonate therapy in the secondary prevention of osteoporotic fractures. Osteoporos Int 24(2):697–705PubMedCrossRef
28.
go back to reference Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62(10):e1–34PubMedCrossRef Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62(10):e1–34PubMedCrossRef
29.
go back to reference Thorlund K, Imberger G, Johnston BC et al (2012) Evolution of heterogeneity (I2) estimates and their 95 % confidence intervals in large meta-analyses. PLoS One 7(7):e39471PubMedCentralPubMedCrossRef Thorlund K, Imberger G, Johnston BC et al (2012) Evolution of heterogeneity (I2) estimates and their 95 % confidence intervals in large meta-analyses. PLoS One 7(7):e39471PubMedCentralPubMedCrossRef
30.
31.
go back to reference Galbraith RF (1988) A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med 7(8):889–894PubMedCrossRef Galbraith RF (1988) A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med 7(8):889–894PubMedCrossRef
32.
33.
go back to reference Johnell O (1997) The socioeconomic burden of fractures: today and in the 21st century. Am J Med 103(2A):20S–25S, discussion 25S-26SPubMedCrossRef Johnell O (1997) The socioeconomic burden of fractures: today and in the 21st century. Am J Med 103(2A):20S–25S, discussion 25S-26SPubMedCrossRef
34.
go back to reference Sandhu SK, Hampson G (2011) The pathogenesis, diagnosis, investigation and management of osteoporosis. J Clin Pathol 64(12):1042–1050PubMedCrossRef Sandhu SK, Hampson G (2011) The pathogenesis, diagnosis, investigation and management of osteoporosis. J Clin Pathol 64(12):1042–1050PubMedCrossRef
35.
go back to reference Black DM, Cummings SR, Karpf DB et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348(9041):1535–1541PubMedCrossRef Black DM, Cummings SR, Karpf DB et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348(9041):1535–1541PubMedCrossRef
37.
go back to reference Reid IR, Cornish J (2012) Epidemiology and pathogenesis of osteonecrosis of the jaw. Nat Rev Rheumatol 8(2):90–96 Reid IR, Cornish J (2012) Epidemiology and pathogenesis of osteonecrosis of the jaw. Nat Rev Rheumatol 8(2):90–96
38.
go back to reference Khosla S, Burr D, Cauley J et al (2007) Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 22(10):1479–1491PubMedCrossRef Khosla S, Burr D, Cauley J et al (2007) Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 22(10):1479–1491PubMedCrossRef
Metadata
Title
Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporosis: a systematic review and meta-analysis
Authors
S.-H. Lee
S.-S. Chang
M. Lee
R.-C. Chan
C.-C. Lee
Publication date
01-03-2014
Publisher
Springer London
Published in
Osteoporosis International / Issue 3/2014
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-013-2575-3

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