Journal of Orthopaedic Translation

S1 File. Minimal dataset of the study.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive medications managing osteoporosis and cancer-related conditions. The frequency of MRONJ in the osteoporosis patients receiving antiresorptive medications is estimated at 0.001%-0.01%, and in oncology patients receiving higher doses is 1%-15%. The pathogenesis of MRONJ is still unclear and probably multifactorial. The prevention strategies for MRONJ remain an active area of research. Suppression of angiogenesis is a proposed pathogenesis of MRONJ. As magnesium (Mg)-based implants have proangiogenic effects, we hypothesized that the biodegradable Mg implant could ameliorate the onset of MRONJ via enhancing angiogenesis. In this study, we aimed to investigate the effects of Mg on the pathological alterations of MRONJ-like lesion, and the role of vascular endothelial growth factor (VEGF)- and calcitonin gene-related peptide (CGRP)-mediated angiogenesis under the pathogenesis of MRONJ. Eight weeks postoperatively, the group implanted with Mg had significantly decreased occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and elevated expressions of VEGFA and CGRP, comparing with the control group. By concurrently inhibiting VEGF receptor-2 and CGRP receptor, the vessel volume and new bone formation in the group implanted with Mg were significantly reduced, meanwhile the occurrence of MRONJ-like lesion and histological osteonecrosis were significantly increased. This was the first study investigating the effects of Mg on MRONJ, that Mg could ameliorate the onset of MRONJ-like lesion, possibly via upregulating VEGF- and CGRP-mediated angiogenesis. Mg-based biodegradable implants have the potential to be developed as a novel internal fixation device with therapeutic value for patients at the risk of MRONJ or with established MRONJ. Future clinical trial shall be conducted to confirm the prevention and treatment outcomes of Mg-based implants.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive medications managing osteoporosis and cancer-related conditions. The frequency of MRONJ in the osteoporosis patients receiving antiresorptive medications is estimated at 0.001%-0.01%, and in oncology patients receiving higher doses is 1%-15%. The pathogenesis of MRONJ is still unclear and probably multifactorial. The prevention strategies for MRONJ remain an active area of research. Suppression of angiogenesis is a proposed pathogenesis of MRONJ. As magnesium (Mg)-based implants have proangiogenic effects, we hypothesized that the biodegradable Mg implant could ameliorate the onset of MRONJ via enhancing angiogenesis. In this study, we aimed to investigate the effects of Mg on the pathological alterations of MRONJ-like lesion, and the role of vascular endothelial growth factor (VEGF)- and calcitonin gene-related peptide (CGRP)-mediated angiogenesis under the pathogenesis of MRONJ. Eight weeks postoperatively, the group implanted with Mg had significantly decreased occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and elevated expressions of VEGFA and CGRP, comparing with the control group. By concurrently inhibiting VEGF receptor-2 and CGRP receptor, the vessel volume and new bone formation in the group implanted with Mg were significantly reduced, meanwhile the occurrence of MRONJ-like lesion and histological osteonecrosis were significantly increased. This was the first study investigating the effects of Mg on MRONJ, that Mg could ameliorate the onset of MRONJ-like lesion, possibly via upregulating VEGF- and CGRP-mediated angiogenesis. Mg-based biodegradable implants have the potential to be developed as a novel internal fixation device with therapeutic value for patients at the risk of MRONJ or with established MRONJ. Future clinical trial shall be conducted to confirm the prevention and treatment outcomes of Mg-based implants.