About this Research Topic
Osteonecrosis of the jaw (ONJ) is an oral lesion involving mandibular or maxillary bones; according to its etiology, it can be can be considered as Medication-related ONJ (MRONJ), osteoradionecrosis, traumatic osteonecrosis, non-traumatic osteonecrosis and spontaneous osteonecrosis.
MRONJ was recently defined as an “adverse drug reaction described as the progressive destruction and death of bone that affects the mandible and maxilla of patients exposed to the treatment with medications known to increase the risk of disease, in the absence of a previous radiation treatment”. MRONJ can severely affect patients' quality of life because of pain, and swallowing, feeding, chewing, and speaking impairment: prevention, diagnosis, and treatment of MRONJ play a fundamental role, even more in MRONJ neoplastic patients who need to maintain a good quality of life to go on with oncological treatments.
MRONJ can be caused by antiresorptive (Bisphosphonates, Denosumab, and Romosozumab) and antiangiogenetic drugs. Since 2003, bisphosphonates have been widely associated with MRONJ; in 2010 Denosumab was introduced for osteoporosis (prevention and treatment) and bone metastasis treatment: it is a monoclonal antibody that targets and binds with high affinity and specificity to RANKL. Romosozumab, approved in 2019, is a monoclonal antibody that targets sclerostin; it is approved for severe osteoporosis in postmenopausal women at high risk of fracture; it is rarely associated with MRONJ.
Antiangiogenetic drugs, such as Bevacizumab, Tirosine Kinase Inhibitors (e.g. Sunitib, Lenvatinib, and Cabozantinib), mTOR inhibitors (e.g. Sirolimus), Aflibercept are associated to MRONJ, particularly in combination with chemotherapy and bisphosphonates.
Many risk factors have to be considered when evaluating a patient’s risk of developing MRONJ. Some factors are drug dependent: type of drug, duration of treatments, cumulative dosage, and route of administration (parenteral/subcutaneous administration of antiresorptive agents are more frequently related to MRONJ than oral one).
Local factors are involved with MRONJ risk: poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease, invasive dental procedures (e.g. tooth extractions), and anatomical conditions. Moreover, different systemic factors are associated with MRONJ, such as underlying disease (solid tumors, multiple myeloma, osteoporosis), age, gender, comorbidities (e.g. cancer, anaemia, coagulopathies, infections, autoimmune disorders, smoking, renal insufficiency), concomitant therapies (e.g. corticosteroids, radiotherapy to head and neck)
Further investigations are needed to better understand the mechanism underlying the development of MRONJ, to properly prevent and treat this disease.
Prevention should be the priority: doctors should be able to identify the risk factors to promote collaboration between different specialists (dentists, endocrinologists, oncologists, hematologists, maxilla facial surgeons), to provide for a preventive dental screening in patients at higher risk for MRONJ and to educate patients to avoid wrong habits, to observe and pay attention to possible signs and symptoms of MRONJ, to establish a regular relationship with their dentist.
Moreover, clear criteria to correctly classify MRONJ, and specific and tailored interventions should be defined
to guide the decision-making process of dentists and oral surgeons
The purpose of this Research Topic is to disseminate as much knowledge as possible regarding particular manifestations of drug-related osteonecrosis of the jaws. In particular, research focusing on the so-called spontaneous MRONJ associated with periodontal and peri-implant diseases will be very welcome. Diagnosis of periodontitis and peri-implantitis are essential for the prevention of MRONJ. This topic is often underreported in the current literature.
Publications (full article but also case reports) of osteonecrosis related not only to bisphosphonates will therefore be welcome.
MRONJ was recently defined as an “adverse drug reaction described as the progressive destruction and death of bone that affects the mandible and maxilla of patients exposed to the treatment with medications known to increase the risk of disease, in the absence of a previous radiation treatment”. MRONJ can severely affect patients' quality of life because of pain, and swallowing, feeding, chewing, and speaking impairment: prevention, diagnosis, and treatment of MRONJ play a fundamental role, even more in MRONJ neoplastic patients who need to maintain a good quality of life to go on with oncological treatments.
MRONJ can be caused by antiresorptive (Bisphosphonates, Denosumab, and Romosozumab) and antiangiogenetic drugs. Since 2003, bisphosphonates have been widely associated with MRONJ; in 2010 Denosumab was introduced for osteoporosis (prevention and treatment) and bone metastasis treatment: it is a monoclonal antibody that targets and binds with high affinity and specificity to RANKL. Romosozumab, approved in 2019, is a monoclonal antibody that targets sclerostin; it is approved for severe osteoporosis in postmenopausal women at high risk of fracture; it is rarely associated with MRONJ.
Antiangiogenetic drugs, such as Bevacizumab, Tirosine Kinase Inhibitors (e.g. Sunitib, Lenvatinib, and Cabozantinib), mTOR inhibitors (e.g. Sirolimus), Aflibercept are associated to MRONJ, particularly in combination with chemotherapy and bisphosphonates.
Many risk factors have to be considered when evaluating a patient’s risk of developing MRONJ. Some factors are drug dependent: type of drug, duration of treatments, cumulative dosage, and route of administration (parenteral/subcutaneous administration of antiresorptive agents are more frequently related to MRONJ than oral one).
Local factors are involved with MRONJ risk: poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease, invasive dental procedures (e.g. tooth extractions), and anatomical conditions. Moreover, different systemic factors are associated with MRONJ, such as underlying disease (solid tumors, multiple myeloma, osteoporosis), age, gender, comorbidities (e.g. cancer, anaemia, coagulopathies, infections, autoimmune disorders, smoking, renal insufficiency), concomitant therapies (e.g. corticosteroids, radiotherapy to head and neck)
Further investigations are needed to better understand the mechanism underlying the development of MRONJ, to properly prevent and treat this disease.
Prevention should be the priority: doctors should be able to identify the risk factors to promote collaboration between different specialists (dentists, endocrinologists, oncologists, hematologists, maxilla facial surgeons), to provide for a preventive dental screening in patients at higher risk for MRONJ and to educate patients to avoid wrong habits, to observe and pay attention to possible signs and symptoms of MRONJ, to establish a regular relationship with their dentist.
Moreover, clear criteria to correctly classify MRONJ, and specific and tailored interventions should be defined
to guide the decision-making process of dentists and oral surgeons
The purpose of this Research Topic is to disseminate as much knowledge as possible regarding particular manifestations of drug-related osteonecrosis of the jaws. In particular, research focusing on the so-called spontaneous MRONJ associated with periodontal and peri-implant diseases will be very welcome. Diagnosis of periodontitis and peri-implantitis are essential for the prevention of MRONJ. This topic is often underreported in the current literature.
Publications (full article but also case reports) of osteonecrosis related not only to bisphosphonates will therefore be welcome.
Keywords: Osteonecrosis, bisphosphonates, denosumab, antioangenetic drugs, prevention, periodontitis, peri-implantitis
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