Review and update on drugs related to the development of osteonecrosis of the jaw

Abstract

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but serious adverse effect of certain drugs, of which bisphosphonates are the most widely known. This pathology is also associated with other medications such as the biologic antiresorptive agent, denosumab and some antiangiogenics such as sunitinib, bevacizumab or aflibercept. Very recently, new medications have also been associated with osteonecrosis of the jaw (ONJ). The objectives were to update the list of medications associated with ONJ, to analyze the fundamental aspects of this list and to describe the level of evidence available. Material and Methods: A narrative bibliographic review was made, using the PubMed-MedLine, DOAJ and SCI-ELO databases. Additional information was obtained through the online Medication Information Centre of the Spanish Agency of Medicines and Medical Devices (AEMPS-CIMA), the websites of the US Food & Drugs Administration (Drugs@FDA) and the European Medicines Agency (EMA). Results: The latest drugs identified as potential facilitators of this pathology include a number of anti-VEGF based antiangiogenic drugs and anti-TKI and different types of immunomodulators. Neither the level of evidence in this association nor the risk are equal for all these drugs. On the other hand, over the coming years, new drugs will be marketed with similar action mechanisms to those that are recognized as having this adverse effect. Conclusions: No effective therapy is currently known for the treatment of ONJ. Therefore, in order to prevent new cases of MRONJ, it is essential for all oral healthcare professionals to be fully up-to-date with the etiopathogenic aspects of this pathology and to be aware of those drugs considered to be a risk.

Comprehensive Study of the Risk Factors for Medication-Related Osteonecrosis of the Jaw Based on the Japanese Adverse Drug Event Report Database

“…Many antiangiogenic agents are associated with MRONJ [ 26 ]. This effect of antiangiogenic agents may differ depending on their mechanism of action [ 7 ].…”

“…Patients may be considered to have MRONJ if they present with the following characteristics: (1) current or previous treatment with antiresorptive or antiangiogenic agents; (2) exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region, which has persisted for over 8 weeks; (3) no history of radiation therapy to the jaws or obvious metastatic disease to the jaws [ 2 ]. Meanwhile, corticosteroids and novel immunomodulators have also been reported to affect osteonecrosis of the jaw [ 6 , 7 ]. BP is also reported to cause bone-related side effects, such as atypical femoral fractures and osteonecrosis of the external auditory meatus [ 8 , 9 ].…”

The Case of Medication-Related Osteonecrosis of the Jaw Addressed from a Pathogenic Point of View. Innovative Therapeutic Strategies: Focus on the Most Recent Discoveries on Oral Mesenchymal Stem Cell-Derived Exosomes

“…Indeed, accumulating evidence suggested the involvement of other antiresorptive and antiangiogenic treatments among the causes of MRONJ, such as bevacizumab, sunitinib, aflibercept and denosumab [11][12][13][14]. More recently, the administration of other antiangiogenics such as dasatinib, erlotinib, imatinib, axitinib, sorafenib and cabozantinib has been associated with MRONJ [15]. A detailed review of the drugs related to the development of MRONJ has been recently published [15].…”

“…More recently, the administration of other antiangiogenics such as dasatinib, erlotinib, imatinib, axitinib, sorafenib and cabozantinib has been associated with MRONJ [15]. A detailed review of the drugs related to the development of MRONJ has been recently published [15]. Today, the nitrogen-BPs (N-BPs) alendronate and zoledronate, and the human monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand (RANKL), denosumab, have been suggested as drugs most commonly associated to the development of MRONJ.…”

Dental Implants Loaded With Bioactive Agents Promote Osseointegration in Osteoporosis: A Review

“…In addition to the implant design, it is necessary to promote osteoinduction and inhibit bone resorption locally in osteoporotic patients ( Lin et al, 2013 ). Systemic administration orally or intravenously provides low bioavailability, which makes it difficult to maintain an effective concentration around the implants and might cause severe side effects, such as necrosis of the jaw bone ( Eguia et al, 2020 ). Local administration ensures adequate drug concentration in the target tissue and reduces toxicity in the non-target areas.…”