Histologic analysis of medication-related osteonecrosis of the jaw compared with antiresorptive-exposed bone and other infectious, inflammatory, and necrotic jaw diseases

Objective. This study characterized histologic features of medication-related osteonecrosis of the jaw (MRONJ) through analysis of tissues from patients and healthy individuals. Study Design. Bone biopsies were collected from various infectious, inflammatory, and necrotic jaw diseases. Samples were divided into bone exposed to bisphosphonates or denosumab, as well as bisphosphonate-related osteonecrosis of the jaw (BRONJ), denosumab-related osteonecrosis of the jaw (DRONJ), and mixed necrosis, enabling us to identify features of single agent necrosis without influence from previous therapies. Hematoxylin and eosin (H&E), receptor activator of nuclear factor kappa-B ligand (RANKL), tartrate-resistant acid phosphatase (TRAP), osteoprotegerin, toluidine blue, CD14, and CD68 staining and micro-computed tomography (micro-CT) analysis were performed. Groups were compared by using analysis of variance (ANOVA). Results. In total, 156 bone samples were collected from 105 patients. MRONJ variants exhibited more infectious infiltration. Bisphosphonate (P<.001) and mixed necrosis (P=.002) demonstrated more RANKL-and TRAP-positive osteoclasts. Denosumab necrosis (P=.007), and bone exposed to bisphosphonates (P=.028) in combination with denosumab (P=.022) demonstrated significantly lower numbers of osteocytes per area. CD14 and CD68 positivity was increased for BRONJ (P=.008; P<.001, respectively). MRONJ variants exhibited the widest trabecular width and decreased medullary space to bone. No diminished vascular network in MRONJ samples was observed. Conclusions. Histologic features differ among MRONJ variants, with oversuppressed bone turnover, dysfunctional bone resorption, and a disturbed osteocyte network as potential mechanisms of pathogenesis.