Should denosumab (Prolia) ever be discontinued?

From the Guidelines

Prolia (denosumab) should not be discontinued without a replacement therapy plan due to the risk of rebound bone loss and increased fracture risk, as evidenced by the European Calcified Tissue Society's recommendation to consider bisphosphonate therapy after stopping denosumab 1.

Key Considerations

• The risk of vertebral fractures increases when denosumab is discontinued, highlighting the need for a planned transition to an alternative osteoporosis medication, such as a bisphosphonate 1.
• The European Calcified Tissue Society suggests that a re-evaluation should be carried out after 5 years of denosumab treatment, and bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover 1.
• The optimal bisphosphonate regimen post-denosumab is currently unknown, and continuation of denosumab can also be considered until results from ongoing trials become available 1.

Management Strategy

• Patients who must stop Prolia should transition to an alternative osteoporosis medication, typically a bisphosphonate like alendronate, immediately after the last Prolia dose is due to prevent rapid bone loss.
• Healthcare providers should create a specific plan that may include bone density monitoring and calcium/vitamin D supplementation for patients who must stop Prolia.
• Any decision to discontinue Prolia should always be made in consultation with a healthcare provider who can assess individual risk factors and develop an appropriate management strategy.

Relevant Evidence

• The European Calcified Tissue Society's recommendation to consider bisphosphonate therapy after stopping denosumab is based on the risk of rebound bone loss and increased fracture risk 1.
• The strongest evidence of benefit from antiresorptive drugs is for treatment with denosumab at the osteoporosis dose of 60 mg every 6 months, which has been demonstrated to reduce the risk of fracture 1.

From the FDA Drug Label

Discontinuation of Prolia therapy should be considered based on individual benefit-risk assessment. Interruption of Prolia therapy should be considered, pending a benefit-risk assessment, on an individual basis. Consider discontinuing Prolia if severe symptoms develop. Consider discontinuing use if severe symptoms develop

Prolia discontinuation should be considered in certain situations, including:

• Individual benefit-risk assessment
• Development of severe symptoms, such as those associated with atypical femoral fractures, serious infections, dermatologic adverse reactions, or musculoskeletal pain
• Based on the clinical judgment of the treating physician and/or oral surgeon in patients with osteonecrosis of the jaw (ONJ) 2

From the Research

Discontinuation of Prolia

• The discontinuation of denosumab, also known as Prolia, is a complex issue that requires careful consideration of the potential risks and benefits 3.
• Studies have shown that discontinuation of denosumab may lead to an increased risk of multiple vertebral fractures, particularly in patients with a high fracture risk 3.
• The European Calcified Tissue Society (ECTS) recommends that clinicians and patients be aware of this potential risk and consider alternative treatments to prevent rapid bone mineral density (BMD) loss and a potential rebound in vertebral fracture risk 3.

Factors to Consider

• The optimal duration of osteoporosis treatment is controversial, and the decision to discontinue denosumab should be based on individual patient factors, including underlying fracture risk, medical comorbidities, and medication burden 4.
• Patients considered at high fracture risk should either continue denosumab therapy for up to 10 years or be switched to an alternative treatment, such as bisphosphonates 3.
• For patients at low risk, a decision to discontinue denosumab could be made after 5 years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover 3.

Comparison with Other Treatments

• Denosumab has been shown to be more effective than bisphosphonates in increasing BMD and reducing bone turnover markers in some studies 5, 6, 7.
• However, the safety profile of denosumab is similar to that of bisphosphonates, and the risk of adverse events, including infections and fractures, is comparable between the two treatments 6.