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

Abstract

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.

Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw

“…Although histopathological definition for diagnosis of ARONJ is yet to be established, several Actinomyces play a role in the pathogenesis of BRONJ [23].…”

Drug-induced osteonecrosis of the jaw: the state of the art

“…The major histopathological finding in ONJ is chronic osteomyelitis accompanied by osteonecrosis (15). Actinomyces colonies (resident bacteria in the oral cavity) are frequently found in contact with necrotic bones in ONJ lesions, supporting the possibility that Actinomyces bacteria could play a key role in the pathogenesis of ONJ (16). Bacteria also stimulate bone resorption through the production of local cytokines and contribute to bone necrosis.…”

Medication‐related osteonecrosis of the jaw – a current review

“…Histology of excised necrotic jaw specimens identified bacteria, viruses and fungi, coexisting in biofilms. Actinomyces may be an important factor in high‐grade osteonecrosis and is isolated in most osteonecrosis specimens. The presence of actinomyces at osteonecrotic sites may be opportunistic because oral actinomyces are common but actinomycosis is uncommon.…”