Osteonecrosis

Aiya Almogaber, PharmD

For years, the American Association of Oral and Maxillofacial Surgeons (AAOMS) has been crafting strategies to tackle medication-related osteonecrosis of the jaws (MRONJ), formerly known as bisphosphonate-related osteonecrosis of the jaws. In an update published in the March 2024 issue of the Journal of Oral and Maxillofacial Surgery, experts from AAOMS explain revised diagnosis and management protocols, medication comparisons, and preventive measures aimed at empowering health care providers and enhancing patient care.

MRONJ affects the jaw bones (mandible and maxilla) but differs from other forms of osteonecrosis primarily in its etiology and clinical presentation. MRONJ is triggered by the use of antiresorptive medications such as bisphosphonates, denosumab (a RANK-L inhibitor), and some monoclonal antibodies, particularly in patients receiving these therapies for cancer-related conditions or osteoporosis. Clinically, MRONJ often presents with exposed bone in the oral cavity, persistent ulcers, localized pain or swelling, and potentially secondary infections.

Joseph Armstrong, DMD, from Ideal Dental of Kannapolis in Concord, NC, said that a routine workup for his patients includes screening for the presence of these abnormalities and asking patients if they are currently taking antiresorptive medications prior to performing certain dental procedures.

“Early detection and management are crucial to alleviate symptoms and prevent further complications,” he said.

Although antiresorptive therapies improve life expectancy, MRONJ may affect patients’ quality of life due to pain; discomfort; anxiety; depression; impaired speech, swallowing, and eating; frequent medical and dental evaluations; and the possible discontinuation of treatment.

According to AAOMS, the major goals of treatment are prevention of MRONJ, prioritization and control of oncologic treatment in patients receiving antiresorptive therapy, support of continued bone health and prevention of fractures, and preservation of quality of life.

Risk factors

Risk factors associated with MRONJ encompass medication-related, demographic, systemic, and oral health variables. Antiresorptive medications such as bisphosphonates and denosumab are the primary culprits, with an increased risk in patients who have malignancies (<5%) compared to those receiving therapy for osteoporosis (<0.05%). The duration of medication therapy also plays a role, with prolonged exposure correlating with higher MRONJ incidence rates.

Pharmacists play an essential role in recognizing MRONJ risks linked to patients’ medication profiles. By identifying individuals taking antiresorptive therapies, they can track usage duration to prevent prolonged exposure. Routine medication counseling can be used to emphasize regular dental checkups and prompt reporting of any abnormal oral symptoms.

Certain oral health factors may contribute to MRONJ risk as well, notably dentoalveolar operations such as tooth extractions, dental implant placements, or periodontal procedures.

Anatomic factors such as mandibular location and denture use can also influence MRONJ risk. Armstrong said variations in jaw anatomy, such as the presence of tori or sharp bony prominences, may predispose individuals to increased mechanical stress and trauma. To prevent this outcome in clinical practice, he screens patients’ mouths.

The mouth’s vascularity and soft tissue thickness can affect wound healing and susceptibility to infection, further impacting the manifestation of MRONJ in affected individuals, Armstrong said.

Additionally, demographic factors such as age or sex, comorbid conditions like anemia or diabetes, and certain medications such as corticosteroids are implicated as risk factors, with variable associations across studies. Susceptible patient populations should be monitored and assessed to lessen the occurrence and impact of MRONJ.

Pharmacists can also reinforce preventive actions to reduce MRONJ risks and relay concerns or observations to the patient’s health care team.

Staging

The staging system for MRONJ has evolved significantly since it was initially introduced in the 2000 AAOMS position paper and later refined in the 2014 update. The system has become widely accepted as a tool for guiding clinicians in treatment planning and outcome assessment. AAOMS views its staging system as a robust framework that avoids overemphasis on radiographic features to mitigate false positives.

Patients at risk of MRONJ may progress from stage 0 (non-exposed bone variant, nonspecific symptoms, absence of necrotic bone) to stage 3 (severe manifestations, pathologic fractures). Stage escalation is indicative of disease progression and the need for more demanding management strategies.

Management strategies

The management strategies for MRONJ outlined by AAOMS emphasize several key points. First, prevention is crucial, especially for patients at risk or those undergoing antiresorptive therapy for other chronic conditions. Strategies such as performing high-risk surgical procedures before starting therapy, using antibiotics and mouth rinses, closing extraction sites effectively, and maintaining good oral hygiene are recommended. Lastly, optimizing and promoting overall patient health through smoking cessation and diabetes control is encouraged.

A multidisciplinary approach involving dental professionals is crucial for patients receiving antiresorptive therapies. Pretreatment dental screening and regular surveillance are highlighted, as early detection and management of potential issues can significantly reduce MRONJ risk. Strategies for asymptomatic patients on antiresorptive therapy for both cancer and osteoporosis, including avoiding osseous injury during dental procedures and using caution with dental implants, are discussed in the update.

Patient education, pain control, infection prevention, and lesion management are also emphasized to preserve quality of life.

The controversial practice of drug holidays before dental procedures is also discussed in the update.

Armstrong describes a drug holiday as a temporary cessation or interruption of medication use. In the context of dentistry and MRONJ prevention, these medications include antiresorptive agents.

“Before initiating a drug holiday, consulting with the patient’s prescribing physician is essential,” he said. Collaboration between health care providers ensures that the patient receives comprehensive and personalized care, minimizing the risk of complications while optimizing oral health outcomes.

In practice, Armstrong considers the patient’s medical history, overall health status, duration and dosage of medication use, and the potential risks and benefits associated with discontinuing treatment.

The recommendation from AAOMS about drug holidays varies based on disease type, treatment duration, and comorbidities. AAOMS encourages individualized decision-making.

Takeaways

While substantial progress has been made in understanding MRONJ and its association with antiresorptive therapies, questions and challenges persist for patients and their health care providers.

Future research efforts must focus on conducting prospective studies to explore the multifactorial etiology of MRONJ and establish data to support the risks associated with different medication classes and dosing principles. The role of nonantiresorptive therapies, genetic markers, biomarkers, and drug holidays in MRONJ detection and management requires rigorous investigation through strong randomized controlled trials. Until these relationships are clearly defined, AAOMS emphasizes the importance of continued research as the foundation for developing evidence-based recommendations that will guide in alleviating MRONJ risks effectively. ■