Bisphosphonate-related osteonecrosis of the jaw: an Italian post-marketing surveillance analysis

Abstract

Objective: Although bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) is well recognized, little is known about it in terms of pathophysiology, epidemiology or management. We analyzed all suspected BRONJ reports sent to the Italian Pharmacovigilance Adverse Event Spontaneous Reporting System (Rete Nazionale Farmacovigilanza [RNF]) to determine their pattern and add new information about this relevant issue.

Research design and methods: All suspected BRONJ sent to the RNF between 2003 and 2011 were retrieved. After a case-by-case assessment procedure, we analyzed BP type, BP exposure time and time since last use.

Results: Between 2003 and 2011, 555 reports of osteonecrosis of the jaw (ONJ) after BP administration were recorded in the RNF. These events occurred mostly in patients affected by cancer (77.84%) in which zoledronate was the most frequently suspected BP. Most patients experienced ONJ after long-term use of the drug (median time of BP exposure being between 1.3 and 8.8 years). Interestingly, 139 (25.05%) cases of ONJ occurred between 2 and 121 months after BP withdrawal.

Conclusion: This study shows that BRONJ can occur much earlier than hitherto reported, adds new data on BRONJ onset following ibandronate treatment and reveals that patients who cease BP-based therapy develop ONJ, raising the question of post-treatment monitoring strategies.

Keywords::

• bisphosphonates
• osteonecrosis of the jaw
• osteonecrosis of the jaw monitoring
• spontaneous reporting

Acknowledgments

The authors wish to thank Maria Giuseppa Sullo for contributing to fruitful discussion on relevant concepts. The authors thank Jean Ann Gilder for text editing.

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