Differences Between Medication-Related Osteonecrosis of the Jaw Caused by Bisphosphonates and Denosumab: Histological, Molecular Biological, and Clinical Studies

双膦酸盐和地诺单抗引起的药物相关性颌骨坏死之间的差异:组织学、分子生物学和临床研究

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作者:Taro Miyoshi, Mitsunobu Otsuru, Kota Morishita, Keisuke Omori, Kei-Ichiro Miura, Saki Hayashida, Satoshi Rokutanda, Yuki Matsushita, Masahiro Umeda, Tomohiro Yamada

Abstract

Purpose Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of antiresorptive agents such as bisphosphonates (BPs) and denosumab (DMB). We investigated whether a difference exists between BP- and DMB-related osteonecrosis of the jaw (ONJ). Patients and methods Histological images of 30 patients with BP-related ONJ and 13 patients with DMB-related ONJ were observed using hematoxylin-eosin and cathepsin K staining. Moreover, bone metabolism markers in the blood and bone mineral density were measured in 18 patients with BP-related ONJ and five patients with DMB-related ONJ. Furthermore, we conducted a quantitative analysis of local bone metabolism-related genes using surgical specimens through real-time reverse transcription polymerase chain reaction. Additionally, a retrospective study of 298 patients with MRONJ examined the differences in the characteristics of BP- and DMB-related ONJ and the factors associated with treatment outcomes. Results Histological examination revealed that patients treated with DMB had more severe osteoclast suppression than those treated with BP. No significant difference was observed in blood-bone metabolism markers between the two drugs; however, the suppression of local bone metabolism-related genes was stronger in patients treated with DMB. Clinical studies indicate that DMB-related ONJ is more frequently observed without osteolysis. Conclusion BP-associated ONJ and DMB-associated ONJ were shown to differ slightly. Clinical studies indicate that osteolysis is often unclear in DMB-related ONJ, and methods of bone resection during surgery need to be established.

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