ASCO and the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) have published a clinical practice guideline on medication-related osteonecrosis of the jaw in the Journal of Clinical Oncology.1 The guideline outlines the latest recommendations in preventing and managing this condition.
“This guideline represents a consensus on the management of medication-related osteonecrosis of the jaw between two diverse groups of providers—oncologists and dentists—who focus on different areas of health,” said Charles L. Shapiro, MD, of the Icahn School of Medicine at Mt. Sinai, Guideline Co-Chair and working group member.
Charles L. Shapiro, MD
The guideline emphasizes the importance of ongoing collaboration between dentists and oncologists in prevention and management of this condition. In addition to Dr. Shapiro, the effort has been led by working group members: Noam Yarom, DMD, of the School of Dental Medicine, Tel Aviv University, Israel, Guideline Co-Chair; Deborah Saunders, DMD, of Northeast Regional Cancer Centre, Canada, MASCC/ISOO liaison; Douglas E. Peterson, DMD, PhD, FDS RCSEd, of UConn Health School of Dental Medicine, ASCO representative; and Kari Bohlke, ScD, ASCO staff.
Establishing a Diagnosis
Bisphosphonates and denosumab are bone-modifying agents traditionally used to treat skeletal metastases in patients with cancer. Although they have been found to be effective in reducing skeletal-related events, spinal cord compression, pathologic fractures, the need for radiation or surgery to bone, and hypercalcemia, both classes of drugs have been associated with the development of medication-related osteonecrosis of the jaw.
Dr. Shapiro said the publication of new recommendations for management of medication-related osteonecrosis of the jaw is timely because the use of bisphosphonates and denosumab are on the rise. “These two classes of drugs are used extensively in palliation of patients with skeletal metastases, to prevent osteoporosis in patients with early-stage cancers, and as anticancer drugs in certain populations,” he said. “Despite their clinical efficacy, we have to keep in mind that medication-related osteonecrosis of the jaw can significantly affect the patient’s quality of life.”
To help providers establish a diagnosis of medication-related osteonecrosis of the jaw, the guideline specifies the following criteria: (1) Current or previous treatment with a bone-modifying agent; (2) Exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region and that has persisted for longer than 8 weeks; and (3) No history of radiation therapy to the jaw or metastatic disease to the jaw.
Keys to Prevention
“In addition to defining medication-related osteonecrosis of the jaw, we addressed the risk factors, staging system, and management after patients develop osteonecrosis,” Dr. Shapiro said. The focus should be on preventing the condition from developing in the first place, he added.
For reducing the risk of medication-related osteonecrosis of the jaw, the guideline outlined four distinct recommendations for treating providers:
(1) Perform a comprehensive dental, periodontal, and oral radiographic exam prior to initiating bone-modifying therapy for patients with cancer. It should be followed by implementation of a medically centered dental care plan that is coordinated between the dentist and the oncologist.
(2) Address modifiable risk factors, such as poor oral health, ill-fitting dentures, invasive dental procedures, tobacco use, and diabetes management, with patients early in the treatment process.
(3) Avoid elective dentoalveolar surgical procedures, such as alveoplasty, implants, and nonmedically necessary extractions during active treatment with a bone-modifying agent at an oncologic dose. Exceptions can be considered, based on the review of the benefits and risks of the proposed procedure conducted by the dental specialist with the patient and oncology team.
(4) Conduct frequent and systematic dental evaluations every 6 to 8 weeks in those patients who have undergone oral surgery, until the surgical site has fully healed.
Due to insufficient evidence about the need for discontinuation of bone-modifying therapy for patients who receive such treatment at an oncologic dose, the new guideline also states that the decision to administer these agents may be deferred at the discretion of the treating physician. Dr. Shapiro said the guideline stresses the importance of these risk-reduction measures because “once the patient develops medication-related osteonecrosis of the jaw, their quality of life may be adversely affected.”
He added that it is important to conduct prescreening dental exams and perform any invasive dental procedures before instituting antiresorptive drugs. “The guideline further emphasizes that patients should receive routine dental care while on bone-modifying agents, including dental exams and cleanings, because poor oral hygiene is a risk factor for medication-related osteonecrosis of the jaw,” said Dr. Shapiro.
Emphasis on Conservative Treatment Approaches
In addition to addressing risk reduction, the guideline outlines specific recommendations for the management of medication-related osteonecrosis of the jaw, with emphasis on conservative treatment approaches. Recommended conservative measures include effective oral hygiene, the use of antimicrobial mouth rinses and antibiotics if clinically indicated, and conservative surgical interventions. “Typically, aggressive surgical interventions are reserved as a last resort when the provider has exhausted all other treatment options,” Dr. Shapiro said.
The guideline specifies that mucosal flap elevation, block resection of necrotic bone, and soft-tissue closure are surgical interventions suitable for those cases of refractory medication-related osteonecrosis of the jaw when symptoms persist or continue to impact function despite initial conservative treatment.
Use of Bone-Modifying Agents
After a diagnosis of medication-related osteonecrosis of the jaw is established, guideline recommendations are less clear on the use of bone-modifying agents. “There is not enough evidence either to support or refute the discontinuation of bisphosphonates or denosumab after the diagnosis of osteonecrosis,” Dr. Shapiro said. “Therefore, this is considered a gray area in the guideline, and we have left the final decision up to the provider. In cases of bony metastases or other complications, it might be compelling to continue the bone-modifying agent.”
Dr. Shapiro said drug pharmacokinetics should be taken into consideration when making the decision about treatment discontinuation. “For example, zoledronic acid has an incredibly long half-life; it stays in the bone literally for years, so it doesn’t make sense to discontinue it from the pharmacologic standpoint, but we left the door open. Clinicians may feel that it’s in the best interest of an individual patient,” he said. “It ultimately boils down to balancing the risk of treatment discontinuation with the potential, but unknown, risk of making osteonecrosis worse.”
A Team Effort
The final guideline recommendation emphasizes the importance of continued communication between the dentist/dental specialist and the oncologist during treatment of medication-related osteonecrosis of the jaw. To facilitate clear communication between the providers, it recommends the use of terms such as “resolved,” “improving,” “stable,” or “progressive” as descriptive measures of the objective/subjective status of a lesion.
“Medication-related osteonecrosis of the jaw management is a team effort between the dentist and the oncologist, and we made an effort to emphasize this throughout the guideline,” Dr. Shapiro concluded. ■
DISCLOSURE: Dr. Shapiro reported no conflicts of interest. For full disclosure of the panel authors, visit www.jco.ascopubs.org.
REFERENCE
1. Yarom N, et al: Medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO clinical practice guideline. J Clin Oncol. July 22, 2019 (early release online).
Originally published in ASCO Daily News. © American Society of Clinical
Oncology. ASCO Daily News, July 23, 2019. All rights reserved.
