Purpose: This study aims to systematically review observational studies evaluating the use of bisphosphonates (BPs) and risk of osteonecrosis of the jaw (ONJ) among cancer patients. Methods: PubMed, Embase, and Cochrane Library were screened from database inception to Aug 2012. 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 were derived by random effects meta-analysis. Subgroup analyses were carried out according to patients' characteristics and route of BP use. Results: We identified eight studies, including 1,389 cases and 569,620 controls. Use of BPs was associated with a significantly increased risk of ONJ (odds ratio (OR) 4.25; 95% confidence interval (CI) 3.67-5.36; I 2=0%). The summary OR was 4.22 (95% CI 3.21-5.54; I2=0%) for adjusted studies. IV BPs were associated with higher risk (OR 4.27; 95% CI 3.38-5.40; I2=0%) than oral BPs (OR 1.18; 95% CI 0.89-1.56; I 2=0%). Hospital-based studies were associated with higher risk estimates than population-based studies. 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 the highest risk. It is important to assess oral health before initiating therapy and to avoid dental procedures during the active phase of intravenous BP therapy.
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