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Review
. 2022 Apr 19;107(5):1441-1460.
doi: 10.1210/clinem/dgab888.

Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS

Athanasios D Anastasilakis  1 , Jessica Pepe  2 , Nicola Napoli  3 , Andrea Palermo  3 , Christos Magopoulos  4 , Aliya A Khan  5 , M Carola Zillikens  6 , Jean-Jacques Body  7
Affiliations
Review

Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS

Athanasios D Anastasilakis et al. J Clin Endocrinol Metab. .

Abstract

Context: Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases (BM). Osteonecrosis of the jaw (ONJ) is a rare but severe condition manifested as necrotic bone lesion or lesions of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed medication-related ONJ (MRONJ).

Objective: We aimed to identify the differences various aspects of MRONJ among distinct patient categories and provide recommendations on how to mitigate the risk and optimally manage MRONJ in each of them.

Methods: A working group of the European Calcified Tissue Society (ECTS) and 2 experts performed an updated detailed review of existing literature on MRONJ incidence, characteristics, and treatment applied in bone diseases with variable severity of skeletal insult, ranging from osteoporosis to prevention of cancer treatment-induced bone loss and SREs in cancer patients with BM.

Results: The risk for MRONJ is much higher in patients with advanced malignancies compared to those with benign bone diseases because of the higher doses and more frequent administration of antiresorptive agents in individuals with compromised general health, along with coadministration of other medications that predispose to MRONJ. The overall risk for MRONJ is considerably lower than the benefits in all categories of patients.

Conclusion: The risk for MRONJ largely depends on the underlying bone disease and the relevant antiresorptive regimen applied. Physicians and dentists should keep in mind that the benefits of antiresorptive therapy far outweigh the risk for MRONJ development.

Keywords: bisphosphonates; bone metastases; denosumab; osteonecrosis of the jaw; osteoporosis.

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Figures

Figure 1.
Figure 1.
Risk factors for antiresorptive agent-related osteonecrosis of the jaw. AFF, atypical femoral fracture; BMA, bone-modifying agents; MM, multiple myeloma; ONJ, osteonecrosis of the jaw; VEGF, vascular endothelial growth factor.
Figure 2.
Figure 2.
Recommendations for prevention of antiresorptive agent-related osteonecrosis of the jaw in patients taking bone-modifying agents (BMA) due to A, osteoporosis, and B, cancer. ONJ, osteonecrosis of the jaw; RCT, randomized controlled trial. *In the absence of RCT.
Figure 2.
Figure 2.
Recommendations for prevention of antiresorptive agent-related osteonecrosis of the jaw in patients taking bone-modifying agents (BMA) due to A, osteoporosis, and B, cancer. ONJ, osteonecrosis of the jaw; RCT, randomized controlled trial. *In the absence of RCT.
Figure 3.
Figure 3.
Recommendations for management of antiresorptive agent-related osteonecrosis of the jaw in patients taking bone-modifying agents (BMA). Staging of antiresorptive agent-related osteonecrosis of the jaw according to the American Association of Oral and Maxillofacial Surgeons (2014). ONJ, osteonecrosis of the jaw; RCT, randomized controlled trial. *In the absence of RCT.
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Comment in

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