Literature review
Osteonecrosis of the jaws in patients treated with monoclonal antibodies: A review of the literature
Introduction: In the last decade, monoclonal antibodies have revolutionized the field of modern medicine. These are proteins designed to bind specifically to certain molecules for the treatment of certain types of cancer and autoimmune disease.
The aim of this study was to analyze the relationship between treatment with monoclonal antibodies and osteonecrosis of the jaws by analyzing the incidence and associated risk factors.
Methods: A total of 3057 results were initially obtained. After an initial screening of articles that did not meet the inclusion criteria, 42 articles were selected for full-text reading. Finally, 13 randomized clinical trials were included.
Results: The total number of patients included was 16259. The mean incidence of osteonecrosis cases was 3.87%. There were 51 mild cases of osteonecrosis (stage 1-2) and 16 severe cases (stage 3). The risk factors analyzed were the use of mismatched prostheses, invasive dental procedures, periodontal disease and the use of corticosteroids.
Conclusions: The mean incidence of monoclonal antibody-induced osteonecrosis was 3.87%. The use of misaligned prostheses, tooth extraction, periodontal disease and the use of corticosteroids may favor the development of monoclonal antibody-induced osteonecrosis.
The mean incidence of monoclonal antibody-induced osteonecrosis was 3.87%. The use of misaligned prostheses, tooth extraction, periodontal disease and the use of corticosteroids may favor the development of monoclonal antibody-induced osteonecrosis.
Studies of higher quality and with longer follow-up time are necessary to reach more conclusive statements.
Monoclonal antibodies (MAs) are molecules that act as substitutes for endogenous antibodies to restore, enhance, or mimic the activity of the immune system1.
MAs have revolutionised the treatment of autoimmune, allergic, and infectious diseases, being useful in cases of multiple sclerosis, bone metastases, and osteoporosis2-4.
Four types of monoclonal antibodies are distinguished according to their origin: murine, chimeric, humanised, and human. The most commonly used and prescribed at present are the humanised antibodies, identified by the suffix -zumab (romosozumab), and the human antibodies, identified by the suffix -umab (denosumab); the latter are less antigenic, better tolerated, and possess a longer halflife. Both act by inhibiting osteoclast activity, thereby reducing bone resorption and increasing bone density3, with a highly specific mechanism of action through inhibition of the receptor activator of nuclear factor-kappa B ligand (RANKL)5.
RANKL is a critical factor in bone resorption, as it plays a fundamental role in the formation, function, and survival of osteoclasts. The RANKL inhibitor is osteoprotegerin, which, similarly to monoclonal antibodies, competes with RANKL for binding to RANK, thereby neutralising its
effects. Thus, inhibition of RANKL permits an increase in bone density6,7.
Owing to their mechanism of action, these agents may have several adverse effects, including increased susceptibility to infections, hepatic injury, and osteonecrosis of the jaws (ONJ), which is an uncommon but serious condition characterised by one or more necrotic bone lesions that are exposed or can be palpated through an intraoral or extraoral fistula in the maxillofacial region, and persist for at least 8 weeks without response to appropriate treatment8,9.
The American Association of Oral and Maxillofacial Surgeons (AAOMS) introduced the staging system to classify the symptomatology of ONJ and facilitate decision-making for its treatment8. (Table 1)
articles
In the past decade, the use of monoclonal antibodies has increased; therefore, the aim of this literature review was to analyse the association between monoclonal antibody therapy and the incidence of ONJ, as well as the risk factors in patients with ONJ treated with monoclonal antibodies.
Ouazzani Touhami, Mohamed
Undergraduate student at the Complutense University of Madrid (UCM).
Ruiz Rincón, Miguel
Undergraduate student at the Complutense University of Madrid (UCM).
Benito López, Paula
Undergraduate student at the Complutense University of Madrid (UCM).
Bazal Bonelli, Santiago
Associate Lecturer on the Postgraduate Specialisation in Oral Surgery and Implantology, Faculty of Dentistry. Complutense University of Madrid (UCM).
Sánchez-Labrador, Luis
Honorary Associate Lecturer. Department of Clinical Dental Specialties. Complutense University of Madrid (UCM).
López-Quiles Martínez, Juan
Senior Lecturer. Director of the Postgraduate Specialisation in Oral Surgery and Implantology, Faculty of Dentistry, Complutense University of Madrid (UCM).