Use of bisphosphonatesis associated with adverse drug reactions such as atypical femoral fractures (AFs) and osteonecrosis of the jaw (ONJ). Understanding the risk factors can help prevent these reactions and help discover the pathogenic mechanisms.

Rebecca S. Bejhed, MSc, PhD, Uppsala University, Sweden, and colleagues aimed to identify risk factors for bisphosphonate-related ONJ and AF. They conducted a case-control study of reports of bisphosphonate-related adverse drug reactions between February 16, 1984 and October 16, 2013 in the Swedish national database of adverse drug reactions.

Study authors compared cases of ONJ (n=167) and AF (n=55) with other bisphosphonate-related adverse drug reactions (n=565) in regards to demographic variables, clinical characteristics, and concomitant drug therapies. 

The data showed a statistically significant difference in time to onset of adverse drug reactions between AF cases and controls (2,156 days vs. 111 days). When comparing ONJ cases vs. controls, statistically significant differences were seen for time to onset (1,240 days vs. 111 days), intravenous administration (40% vs. 20%), dental procedures (49% vs. 0.2%), prostheses (5% vs. 0%), cancer disease (44% vs. 12%), multiple myeloma (21% vs. 1%), rheumatoid arthritis (14% vs. 5%), and treatment with antineoplastic drugs and oxycodone. 

Study findings further support the risk factors previously identified for ONJ, which included intravenous bisphosphonate administration, invasive dental procedures, dental prostheses, cancer (myeloma in particular), and possibly long-term bisphosphonate treatment. A presumed further risk factor is rheumatoid arthritis. Among cases of AF, only long-term bisphosphonate treatment was more common. Researchers added that the “lack of overlap of risk factors between ONJ and AF suggests different pathogenic mechanisms.”

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