Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Microbiome: Clinical Risk Factors, Pathophysiology and Treatment Options

Abstract

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a serious health condition, impacting the lives of many patients worldwide. The condition challenges clinical care due to its complex etiology and limited therapeutic options. A thorough understanding of the pathophysiological and patient-related factors that promote disease development is essential. Recently, the oral microbiome has been implicated as a potential driver and modulating factor of BRONJ by several studies. Modern genomic sequencing methods have provided a wealth of data on the microbial composition of BRONJ lesions; however, the role of individual species in the process of disease development remains elusive. A comprehensive PubMed search was conducted to identify relevant studies on the microbiome of BRONJ patients using the terms "microbiome", "osteonecrosis of the jaws", and "bisphosphonates". Studies focusing on symptoms, epidemiology, pathophysiology, risk factors, and treatment options were included. The principal risk factors for BRONJ are tooth extraction, surgical procedures, and the administration of high doses of bisphosphonates. Importantly, the oral microbiome plays a significant role in the progression of the disease. Several studies have identified alterations of microbial composition in BRONJ lesions. However, there is no consensus regarding bacterial species that are associated with BRONJ across studies. The bacterial genera typically found include Actinomyces, Fusobacterium, and Streptococcus. It is postulated that these microbes contribute to the pathogenesis of BRONJ by promoting inflammation and disrupting normal bone remodeling processes. Current therapeutic approaches are disease-stage-specific and the necessity for more effective treatment strategies remains. This review examines the potential causes of and therapeutic approaches to BRONJ, highlighting the link between microbial colonization and BRONJ development. Future research should seek to more thoroughly investigate the interactions between bisphosphonates, the oral microbiome, and the immune system in order to develop targeted therapies.

Keywords: antiresorptive drug-related osteonecrosis of the jaw (ARONJ); bisphosphonate-related osteonecrosis of the jaw (BRONJ); oral microbiome; pathophysiology.

Figure 1

The pathophysiology of osteonecrosis of the jaw is based on five main factors: immune dysfunction, class-dependent effects of bisphosphonate (BP), bone remodeling, inflammation/infection, and the oral microbiome. The magnified area depicts the most abundant bacteria of the microbial composition commonly found within necrotic bone. The white arrow indicates bacterial migration from soft tissue to the exposed bone ↓ = decreased expression, ↑ = increased expression. Clinical image shows exposed bone with a necrotic lesion located on the left alveolar ridge of the edentulous maxilla (figure created with BioRender).

Figure 2

BRONJ of the lower jaw following implant placement. (A): exposed bone in the oral cavity; (B): panoramic radiograph showing a bone sequester; (C): intraoperative exposure of the sequester; (D): removed bone sequester.