Actinomyces osteomyelitis in bisphosphonate-related osteonecrosis of the jaw (BRONJ): the missing link?

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare complication of bisphosphonate treatment characterized by the development of exposed, necrotic bone in the jaw with inflammatory signs. The pathogenesis of BRONJ is not yet fully understood. This review analyzes the evidence supporting the hypothesis that BRONJ may be considered as a bisphosphonate-induced Actinomyces infection of the jaw according to the modified Koch's postulates. The main arguments relies on the following factors: (1) the high prevalence of isolation of Actinomyces from bone BRONJ lesions (73.2 % in retrospective series); (2) the similar pathological appearance of BRONJ and Actinomyces osteomyelitis in most studies, although BRONJ lesions without inflammation have been reported; (3) the high incidence of events that disrupt the normal mucosal barrier as a necessary trigger to develop BRONJ in bisphosphonate-exposed patients; (4) the predilection of bisphosphonate-induced osteonecrosis for the bones of the jaws; and (5) the favorable response of BRONJ on treatment that is active on Actinomyces. If BRONJ confirms to be a bisphosphonate-induced Actinomyces osteomyelitis of the jaw, this has major consequences for the prevention and treatment of this condition.