Various Therapeutic Methods for the Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) and Their Limitations: A Narrative Review on New Molecular and Cellular Therapeutic Approaches
<p>Case 1 with MRONJ Stage 0: Clinical photos, panoramic view, and computed tomography imaging showing non-significant findings on the maxillary right posterior area. An 81-year-old female patient with a history of taking oral alendronate for five years complained of pain after removing the right upper second premolar five months before. There were no specific findings other than slight soft tissue depression in the area and hard tissue defect presumed to be an extraction socket.</p> "> Figure 2
<p>Case 2 with MRONJ Stage 1: Clinical photo, panoramic view, and computed tomography imaging including three-dimensional reconstruction showing exposed alveolar bone on the anterior maxillary area. An 89-year-old female patient with a history of oral alendronate for more than four years and intravenous administration of denosumab for one year showed the exposed bone after extracting the left upper central incisor three months ago. She reported no symptoms such as pain other than exposed bones. There was no sign of infection, including pus discharge on the exposed bone.</p> "> Figure 3
<p>Case 3 with MRONJ Stage 2: Clinical photo, panoramic view, and computed tomography imaging including three-dimensional reconstruction showing exposed alveolar bone with pus discharge on the right mandibular posterior area. A 68-year-old female patient with a history of intravenous administration of ibandronate for eight years and intravenous administration of denosumab for the last year complained of facial swelling, severe pain, and pus discharge. She had undergone extraction of the right lower second molar at the private dental clinic to relieve the facial swelling and pain. Symptoms were relieved slightly after extraction but worsened again after two weeks. As a result of the examination, exposed bone and infection signs were observed.</p> "> Figure 4
<p>Case 4 with MRONJ Stage 3: Clinical photo, panoramic view, and computed tomography imaging including three-dimensional reconstruction showing extraoral fistula and necrotic bone on the mandibular left anteroposterior area. An 80-year-old female patient with a history of intravenous administration of ibandronate and denosumab for one year was presented with inflammation and skin fistula on the chin area. She had undergone periodontal treatment on the left lower posterior teeth three months ago due to a periodontal abscess, but she was referred for recurrence with facial swelling from a private dental clinic. Bony lesions involving the inferior border of the mandible and the presence of extraoral fistula were observed.</p> ">
Abstract
:1. Introduction
2. Staging and Possible Hypothesis of the Pathogenesis of MRONJ
2.1. Staging of MRONJ and Treatment Strategies
2.2. Possible Hypothesis of Pathogenesis
2.2.1. Suppression of Bone Remodeling
2.2.2. Inhibition of Angiogenesis
2.2.3. Infection and Inflammation
2.2.4. Toxicity to Soft Tissues
2.2.5. Oxidative Stress
3. Various Therapeutic Methods for MRONJ
3.1. Medication
3.2. Surgical Treatment
3.3. Application of Regenerative Materials
3.4. HBO and OT
4. Promising Molecular and Cellular Therapeutic Methods for MRONJ
4.1. Teriparatide
4.2. MSC Therapy
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Drugs | Type of Drug | Indications |
---|---|---|
Alendronate Clodronate Etidronate Ibandronate Pamidronate Risedronate Tiludronate Zoledronate | Bisphosphonates | Osteoporosis, Paget’s disease, bone metastases of malignancies, hypercalcemia of malignancy |
Denosumab | Inhibitor of receptor activator of nuclear factor-kappa B ligand | Osteoporosis, bone metastases of malignancies, hypercalcemia of malignancy |
Sunitinib Sorafenib | Tyrosine kinase inhibitors | Metastatic cancers (breast, renal, lung, colorectal) |
Bevacizumab Rituximab | Vascular endothelial growth factor inhibitors | Glioblastoma, metastatic cancers (breast, renal, lung, colorectal) |
Stage | Clinical Manifestation | Strategies for Management |
---|---|---|
At risk | No apparent necrotic bone | Patient education, no treatment required |
0 | No clinically necrotic or exposed bone with nonspecific clinical and radiographic findings | Systemic medication, including antibiotics and pain-killers when indicated |
1 | Exposed necrotic bone or intraoral fistula with no symptoms and no infection | Patient education, oral antibacterial rinse, close clinical follow-up |
2 | Exposed necrotic bone or intraoral fistula showing symptoms and signs associated with infection | Antibacterial oral rinse, systemic medication with antibiotics and pain-killers, debridement reducing the volume of necrotic bone for infection control |
3 | Exposed necrotic bone or intraoral fistula showing symptoms and signs associated with infection + exposed necrotic bone invading the inferior border of the mandible or the sinus floor of the maxilla and/or extraoral fistula and/or oroantral fistula | Antibacterial oral rinse, medication with antibiotics and pain-killers, surgical treatment including open debridement/resection for long-term control of symptoms and infection |
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On, S.-W.; Cho, S.-W.; Byun, S.-H.; Yang, B.-E. Various Therapeutic Methods for the Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) and Their Limitations: A Narrative Review on New Molecular and Cellular Therapeutic Approaches. Antioxidants 2021, 10, 680. https://doi.org/10.3390/antiox10050680
On S-W, Cho S-W, Byun S-H, Yang B-E. Various Therapeutic Methods for the Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) and Their Limitations: A Narrative Review on New Molecular and Cellular Therapeutic Approaches. Antioxidants. 2021; 10(5):680. https://doi.org/10.3390/antiox10050680
Chicago/Turabian StyleOn, Sung-Woon, Seoung-Won Cho, Soo-Hwan Byun, and Byoung-Eun Yang. 2021. "Various Therapeutic Methods for the Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) and Their Limitations: A Narrative Review on New Molecular and Cellular Therapeutic Approaches" Antioxidants 10, no. 5: 680. https://doi.org/10.3390/antiox10050680