Is oral bisphosphonate-related osteonecrosis of the jaw an endemic condition?

Since the introduction of bisphosphonates to treat diseases that affect bone remodelling, there has been an increasing number of cases of bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ). Epidemiological data regarding BRONJ vary widely between studies, and a number of potential methodological biases have been detected. In some small preliminary studies, single nucleotide polymorphisms associated with an increased risk of BRONJ among cancer patients have been identified. However, genetic susceptibility to oral BP-related BRONJ has not previously been discussed. We suggest that epidemiological variability could be related to the existence of a susceptibility factor particularly prevalent in the population of a well-defined geographical region. To support our hypothesis we performed a search for published case series, only including those with at least 10 patients detected in a single city or a delimited geographical region; this showed that 55% of reports came from Mediterranean countries such as Italy, Israel, Spain and France. The finding does not appear to be conditioned by publication bias. Furthermore, conditions such as classic Kaposi sarcoma and beta-thalassaemia, though not exclusive to the Mediterranean region, also have a high prevalence in that area. We speculate that some of the patients included in the selected US and Australian series may be of Spanish or Italian descent. With an ageing population, the prevalence of osteoporosis will increase, and the number of cases of oral BP-related BRONJ may rise exponentially. Identification of risk groups with susceptibility to BRONJ will arise caution when prescribing BPs and will allow new preventive and therapeutic strategies to be developed.