Macrophages and bisphosphonate-related osteonecrosis of the jaw (BRONJ): evidence of local immunosuppression of macrophages in contrast to other infectious jaw diseases

Alteration of macrophage viability, differentiation, and function by bisphosphonates

“…These data indicate the influence of BPs on several cellular stages including monocytes, differentiating macrophages, and macrophages. Our results were consistent with the data shown in in vivo studies (Hoefert et al, 2015;Kyrgidis et al, 2017;Wehrhan et al, 2017) that BPs regulated the monocyte-and macrophage-mediated immune response by suppressing the differentiation of CD68 + macrophages. It could be possible that the reduction in CD68 + macrophages is compensated by the increase in CD14 + monocyte population as shown in the CD68/CD14 ratio (Hoefert et al, 2015;Kyrgidis et al, 2017).…”

“…It has been suggested that BPs initiate BRONJ by several mechanisms such as suppression of bone turnover (Coxon et al., ; Idris et al., ; Patntirapong et al., ) and the cytotoxicity of oral mucosal cells (Ravosa et al., ). However, recent findings have led to the hypothesis that macrophages could play a prominent role in the development of BRONJ (Hoefert, Schmitz, Weichert, Gaspar, & Eufinger, ; Kyrgidis et al., ; Wehrhan et al., ). The data in this study support this hypothesis.…”

“…ZA administration for 48 hr increases CD14 + monocyte population (Kyrgidis et al., ). Notably, biopsies performed in the affected areas of BRONJ cases result in the altered ratio of CD68/CD14 in contrast to the osteoradionecrosis group and the osteomyelitis group (Hoefert et al., ). These data indicate the influence of BPs on several cellular stages including monocytes, differentiating macrophages, and macrophages.…”

Diabetes as a Risk Factor for Medication-Related Osteonecrosis of the Jaw

“…Similarly, reduced neutrophil activity and impaired chemotaxis were demonstrated in individuals diagnosed with MRONJ, independent of BP treatment (Favot et al 2013). Furthermore, compromised macrophage function at MRONJ sites was also recently demonstrated (Hoefert et al 2014). In patients with metastatic prostate cancer treated with docetaxel and zoledronic acid, leukopenia induced by chemotherapy was suggested as a risk factor for MRONJ, perhaps by aggravating oral cavity infection mediated by mucositis (Miyazaki et al 2012).…”

Zoledronate but not denosumab suppresses macrophagic differentiation of THP-1 cells. An aetiologic model of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

“…Recently, Hoefert et al [33] demonstrated an altered macrophage profile at BRONJ sites in contrast to other infectious jaw diseases as evidence for a disturbed function of local macrophages. Macrophages are important for innate and adaptive immune responses, and they are present in the oral mucosa, and infections increase macrophage recruitment to these sites [34].…”