Abstract
It is yet unknown whether the intravenous administration route alone can fully account for the exacerbation of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this retrospective study was to identify the potential role of the bisphosphonate (BP) administration route as an independent prognostic factor for non-cancerous, stage III MRONJ patients. Bone samples were retrospectively obtained from two groups of osteoporosis patients who underwent surgery for the treatment of stage III MRONJ. Among the subjects, 10 had a history of only oral BP consumption and 10 of intravenous (IV) BP administration. The samples were assessed for osteoclast morphology and immunohistochemical expression of the receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and potassium calcium-activated channel subfamily N member 4 (Kcnn4). Although the osteoclasts derived from both groups exhibited no significant differences in the mean quantity, diameter, and nuclearity, significantly attenuated tartrate-resistant acid phosphatase activity was noted among the IV BP-induced MRONJ bones compared to those of the oral BP group. Significant suppression of the RANKL/OPG ratio and Kcnn4 expression among the retrieved bones of IV BP group patients was also noted. Our results indicate the potential of the BP administration route as an independent prognostic factor for advanced-stage MRONJ, regardless of the dosage or indication for which the BP was prescribed.
Highlights
III, patients for whom the presence of necrotic bone was not confirmed via surgical biopsy, patients with a history of bisphosphonate or denosumab consumption for the management of conditions other than osteoporosis, and those documented to suffer from medical conditions that are known to affect bone regeneration such as anemia, diabetes, and a history of prolonged steroid treatment
Quantitative analysis of the number of osteoclasts within the region of interest (ROI) indicated no significant differences between the two groups (Figure 1d, Table 2)
Taken together with earlier observations that a decreased receptor activator of NF-κB ligand (RANKL)/OPG ratio leads to suppressed bone turnover in Medication-related osteonecrosis of the jaw (MRONJ) patients [4,53,70], our results provide compelling evidence that the administration route of bisphosphonates is an essential determinant of the severity of the disease
Summary
Medication-related osteonecrosis of the jaw (MRONJ) has emerged as a devastating side effect induced secondary to long-term administration of antiresorptive medications since its first description in 2003 [1,2,3,4]. The complex issue related to the unfathomed complex pathophysiology of this disease has led to the establishment of several fundamental milestone theories and subsequent novel treatment strategies for MRONJ patients. Owing to these innovative techniques, it is expected that effective downstaging and management of MRONJ from its earliest stages to the most advanced cases, even for those with concomitant osteo-metabolic diseases, could be possible [6,7,8,9]
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