4.5 Article

The role of M1 and M2 macrophage polarization in progression of medication-related osteonecrosis of the jaw

Journal

CLINICAL ORAL INVESTIGATIONS
Volume 25, Issue 5, Pages 2845-2857

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00784-020-03602-z

Keywords

Jaw diseases; Denosumab; Bisphosphonate-associated osteonecrosis of the jaw; Zoledronic acid; Alendronate; Macrophage; Phenotype

Funding

  1. NIH/NIDCR [R01 DE019465]

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This study investigated the relationship between M1 and M2 macrophage polarization and clinical stage in MRONJ patients. Early-stage patients showed a switch towards M2 phenotype, while advanced-stage patients demonstrated a shift towards the M1 phenotype. Macrophage density of both M1 and M2 subsets was significantly enhanced in patients receiving bisphosphonates.
Objectives The aim of this study was to investigate the relationship between M1 and M2 macrophage polarization and clinical stage in patients with medication-related osteonecrosis of the jaw (MRONJ) who underwent treatment with bisphosphonates or denosumab. Materials and methods M1 and M2 macrophage density and expression of interleukin (IL)-6 and IL-10 were assessed on biopsies of mucosal tissues surrounding necrotic bone in 30 MRONJ patients with stages 1-3 and controls. For identification of M1 and M2 macrophages, double CD68/iNOS and CD68/CD206 immunofluorescence staining was conducted, respectively. Computer-assisted immunofluorescence quantification of markers was performed. Results Early stage 1 MRONJ patients showed a switch toward the M2 phenotype, as indicated by the higher density of M2 macrophages, the decreased M1/M2 ratio, and the upregulation of IL-10. MRONJ patients with advanced stages 2 and 3 showed a shift toward M1-polarized macrophages, as suggested by the higher density of M1 macrophages, the increased M1/M2 ratio, and the overexpression of IL-6. The macrophage density of both M1 and M2 subsets was significantly enhanced in patients receiving bisphosphonates compared with those receiving denosumab. Conclusions The M1-M2 macrophage polarization status in mucosal tissues bordering necrotic bone correlates with clinical stage of MRONJ. Patients with early-stage MRONJ show a switch toward M2-polarized macrophages, while MRONJ patients with advanced stage demonstrate a shift toward the M1 phenotype.

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