Management of Denosumab-Related Osteonecrosis of the Jaw

Classification and Treatment by Stage

• The American Society of Clinical Oncology recommends that the treatment of denosumab-related osteonecrosis of the jaw be based on stage classification and follow a specific management protocol according to the severity of the lesion, with periodic evaluation every 8 weeks by a dental specialist in communication with the oncologist 1
• For stage 1, asymptomatic bone exposure/necrosis without infection, treatment includes antibacterial mouthwashes (chlorhexidine) 1
• For stage 2, bone exposure/necrosis with infection, treatment includes symptomatic treatment with oral antibiotics, topical antibacterial mouthwashes, pain control, and debridement to alleviate soft tissue irritation and control infection 1
• For stage 3, bone exposure/necrosis with severe complications, treatment includes symptomatic treatment with oral antibiotics, topical antibacterial mouthwashes, pain control, and surgical debridement or resection for long-term palliation of infection and pain 1

Considerations for Continuing or Suspending Denosumab

• The temporary suspension of denosumab may be beneficial for the resolution of osteonecrosis of the jaw, due to its different pharmacological characteristics compared to bisphosphonates, with low-level evidence suggesting improvement in osteonecrosis resolution 1
• The potential benefit of temporary suspension must be balanced with the risk of skeletal-related events 1
• Communication between the dental specialist and the oncologist is essential for making decisions about suspending or restarting denosumab 1

Evaluation and Follow-up of the Lesion

• The expert panel recommends that the status of the lesion be described by the dental specialist as resolved, improving, stable, or progressive, with resolution defined as complete mucosal coverage, no pain, and no infection/inflammation 2
• The course of osteonecrosis can affect decisions on local and/or systemic treatment 2

Prevention of Osteonecrosis of the Jaw

• Before starting denosumab treatment, a complete dental and periodontal examination should be performed, including radiographs 3
• Necessary invasive dental procedures should be completed before starting denosumab 3
• During denosumab treatment, excellent oral hygiene should be maintained, and invasive dental procedures should be avoided when possible 4

Advantages of Denosumab vs. Bisphosphonates in Managing Osteonecrosis

• Denosumab does not incorporate into the bone matrix, and bone turnover is not suppressed after its interruption 5
• Denosumab does not require monitoring of renal function, unlike zoledronic acid 4, 6
• The risk of osteonecrosis of the jaw is 1-2% for both denosumab and bisphosphonates 6

Precautions and Special Considerations

• Denosumab has a higher risk of hypocalcemia compared to zoledronic acid (13% vs 6%) 6
• All patients should receive calcium and vitamin D supplements to prevent hypocalcemia 6

Dental Evaluation Before Denosumab Initiation

Guideline-Based Recommendation

• The European Society for Medical Oncology (ESMO) recommends that patients have a dental evaluation and, when feasible, complete invasive dental treatments before initiating denosumab, with a Grade III, A recommendation, for all patients with bone metastases from solid tumors, including renal cell carcinoma 7, 8, 9, 10, 11
• The ESMO Clinical Practice Guidelines explicitly state that dental evaluation is required before starting bone-targeting agents (BTAs) including denosumab, with a Grade III, A recommendation, for patients with bone metastases from solid tumors, including renal cell carcinoma 7, 8, 9, 10, 11

Special Considerations for Bed-Bound Patients

• Denosumab is recommended for patients with advanced renal cancer and bone metastases with life expectancy ≥3 months, according to the ESMO guidelines 8, 10
• The dental evaluation can be performed at bedside if necessary, and it is crucial to prevent osteonecrosis of the jaw (ONJ), a severely morbid complication that can cause exposed necrotic bone, infection, severe pain, and requires prolonged antibiotic therapy and potentially surgical debridement 8

Practical Implementation

• If dental evaluation is truly impossible, the clinical rationale for proceeding without dental evaluation should be documented, and meticulous oral hygiene protocols should be in place, including prophylactic chlorhexidine mouthwashes, and close monitoring for early signs of ONJ 9, 8

Osteonecrosis of the Jaw (ONJ) Risk and Management in Patients Receiving Denosumab

Invasive Dental Procedures and ONJ Risk

• Invasive dental procedures that expose or traumatize jawbone—such as tooth extractions, dental implant placement, oral surgery, and periodontal surgery involving bone—are identified as risk factors for osteonecrosis of the jaw (ONJ) in patients treated with denosumab, whereas routine restorative work (e.g., fillings) does not increase ONJ risk. 12

Timing of Denosumab Around Invasive Dental Work

• When an invasive dental procedure is required while a patient is on denosumab, it is advisable to delay the next denosumab injection for 14–21 days after the procedure to allow initial bone healing, provided this is clinically appropriate. 12
• Prior to initiating denosumab therapy, completing any necessary invasive dental work is recommended to reduce the likelihood of ONJ. This recommendation is supported by both the 2011 and 2020 oncology literature. [12][13]

Consequences of Denosumab Discontinuation and Mitigation Strategies

• Abrupt cessation of denosumab without transitioning to another osteoporosis medication results in rapid bone loss and a markedly increased risk of multiple vertebral fractures, which can begin as early as 7 months after the last dose. 13
• If denosumab must be stopped for more than 6 months, patients should be switched to a bisphosphonate to prevent rebound bone loss and associated fracture risk. 13