Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is primarily an adverse side effect of denosumab or bisphosphonates (particularly when used at high doses to prevent skeletal-related events [SREs] in patients with cancer and bone metastases) or possibly anti-angiogenic cancer treatment. While the implementation of preventive measures over recent years has reduced the risk of MRONJ in patients with bone metastases due to cancer, it is imperative to balance the risk of MRONJ against the beneficial effects of treatment with denosumab or bisphosphonates on the skeletal health of patients. Despite growing awareness of MRONJ within the medical community, there is a lack of large-scale, prospective clinical studies in this rapidly evolving field. Discussing preventive measures with patients and implementing them, both before and during treatment with bisphosphonates or denosumab, is the best option to reduce the risk of MRONJ. In particular, avoiding bone trauma and preventing and treating dental infections before and during denosumab or bisphosphonate therapy is crucial to minimize the risk of MRONJ. If MRONJ develops, conservative (non-surgical) treatment can provide symptom relief, but achieving mucosal closure remains challenging. When management of symptoms and mucosal healing are the ultimate goals of therapy, or after failure of conservative treatment, a surgical approach may be beneficial. This critical review, based on a best-evidence review of currently available literature, provides clear practical guidelines to help to prevent, manage and treat MRONJ. Overall, a multidisciplinary, pragmatic approach to MRONJ should be adopted, prioritizing patient's quality of life and management of their skeletal malignant disease.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition

“…Risk of subsequent fracture is significantly elevated for patients at all levels of BMD (22,24,62,63) and patients with BMD results that fall outside the "usual" diagnostic parameters for osteoporosis can benefit from pharmacotherapy. (67) For the more typical osteoporosis patient, as noted by the Canadian Association of Oral and Maxillofacial Surgeons, "[d]elaying the initiation of bisphosphonate therapy pending a dental evaluation rarely would seem necessary…." (19)(20)(21)49,64,65) Consider a patient's oral health before starting pharmacologic therapy because of rare instances of osteonecrosis of the jaw (ONJ) occurring in patients taking bisphosphonates or denosumab for osteoporosis.…”

“…(134) The exact incidence of ONJ remains unknown but is believed to be 0.001% or less annually in the general population (66,135) In patients with osteoporosis who are taking usual doses of bisphosphonates, the incidence is estimated to be only slightly higher-somewhere in the range of 0.001% (1/100,000) and 0.01% (1/10,000). (67,123,135) Denosumab-related ONJ, for example, has rarely been reported in patients who do not have cancer and who are being treated only for osteoporosis. (67,123,135) Denosumab-related ONJ, for example, has rarely been reported in patients who do not have cancer and who are being treated only for osteoporosis.…”

“…The International Task Force on Osteonecrosis of the Jaw, supported by 14 international societies, names dental extraction and suppuration as the two most important risk factors for osteoporosis patients on bisphosphonates or denosumab. (66,67,134,139) There are steps that clinicians and patients can take to try to reduce the risk of ONJ. (66) Although roughly one-third of ONJ cases do not have any clear preceding event, the most common preceding events are local bone infection or trauma.…”

“…(66) (More information on the risk factors for oncology patients as well as other factors that may increase risk can be found in the International Task Force's most recent review article.) (66,67,138,140) Minor dental procedures like fillings, inlays, crowns, and scaling can be performed routinely and even procedures like tooth extractions and implant surgery can be performed if needed on osteoporosis patients taking antiresorptives. (66,67,134,139) There are steps that clinicians and patients can take to try to reduce the risk of ONJ.…”

A review and guide to drug‐associated oral adverse effects—Dental, salivary and neurosensory reactions. Part 1

“…Denosumab reduces bone resorption by binding to the receptor activator of nuclear factor‐kappa B ligand (RANKL), which causes decreased formation and activity of osteoclasts, and its association with MRONJ is well established . Longer treatment duration and higher doses are correlated with an increased risk for MRONJ.…”