Assessing the risk of osteonecrosis of the jaw (onj) due to bisphosphonates (bp) therapy in the secondary prevention of osteoporotic fractures

Introduction: Clinical trials indicate that oral BP reduce the incidence of osteoporotic fractures up to 60%. Although the safety of BP appears similar to placebo, adverse reaction reports have suggested an association between BP use and ONJ. On this concern, no epidemiological study including ‘validated’ cases of ONJ has been still conducted. Methods: A case-control study was nested into a cohort of 65,220 fractured osteoporotic patients. An Adjudication Committee selected codes plausibly related to ‘true’ cases of ONJ according to two levels of contiguity: level I ‘possibly contiguous with ONJ’ (e.g. 730.08 ‘multiple bone infections, site unspecified’), level II ‘probably contiguous with ONJ’ (e.g. 526.4 ‘jaw inflammation’). Up to 20 controls were matched to each case according to gender, age (±3 years), month and year of the cohort entry. Odds Ratio [OR; 95% Confidence Intervals (CIs)] of being exposed to BPs among cases vs. controls were estimated through conditional logistic regression model. Multivariable analysis includes use of steroids, proton pump inhibitors and diabetes as confounders. Results: Among (43 level I, 61 level II) 104 cases of ONJ the odds of being exposed to BPs was not different from controls (OR = 1.1; 95% CI: 0.6–1.1). When the analysis was restricted to level II cases, OR was 2.8 (95% CI, 1.3–5.9) higher among current users (last prescription within 1 year before the case’s date) of BP than never users. Conclusions: These findings seem to suggest an association between use of oral BP and ONJ. Further analyses on definitively validated cases are needed.