When to discontinue Prolia (denosumab)?

From the Guidelines

Prolia (denosumab) should be stopped and transitioned to an alternative osteoporosis medication, such as a bisphosphonate, within 6 months of the last injection to prevent rebound bone loss and increased fracture risk, as recommended by the most recent guidelines 1. When considering stopping Prolia, it is essential to evaluate the patient's specific fracture risk, bone mineral density, and overall health status. The decision to stop Prolia should always be made in consultation with a healthcare provider. Some key considerations for stopping Prolia include:

• Preparing for invasive dental procedures to reduce the risk of osteonecrosis of the jaw
• Planning pregnancy
• Severe side effects, such as serious infections or atypical fractures
• Transitioning to an alternative osteoporosis medication, like a bisphosphonate (alendronate 70mg weekly or zoledronic acid 5mg IV yearly), to prevent rapid bone loss after Prolia discontinuation, as suggested by the American College of Physicians 1. The American College of Physicians guideline recommends that patients at low risk for fracture should be considered for drug discontinuation after 3 to 5 years of use, and those who discontinue therapy should have their risk for fracture reevaluated periodically 1. However, denosumab discontinuation is associated with multiple vertebral fractures in some patients, emphasizing the importance of careful consideration and alternative treatment planning before stopping Prolia 1. In general, the management of osteoporosis should be individualized, taking into account the patient's specific needs and risk factors, as outlined in the guidelines from the American College of Physicians 1 and the American College of Rheumatology 1.

From the FDA Drug Label

Interruption of Prolia therapy should be considered, pending a benefit-risk assessment, on an individual basis. If Prolia treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy Consider discontinuing Prolia if severe symptoms develop. Consider discontinuing use if severe symptoms develop

Stopping Prolia should be considered in the following situations:

• When a patient presents with an atypical femur fracture, pending a benefit-risk assessment on an individual basis.
• When severe symptoms of dermatologic adverse reactions, musculoskeletal pain, or other adverse events develop.
• After evaluating an individual's benefit-risk before initiating treatment with Prolia, and periodically thereafter. If Prolia treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy 2.

From the Research

Stopping Prolia (Denosumab) Treatment

• The decision to stop Prolia treatment should be made after careful consideration of the patient's individual risk factors and bone health status 3.
• Studies have shown that discontinuation of denosumab can lead to a rapid decrease in bone mineral density (BMD) and an increased risk of vertebral fractures 3, 4.
• The European Calcified Tissue Society (ECTS) recommends re-evaluation of denosumab treatment after 5 years, and consideration of alternative treatments for patients at high fracture risk 3.
• For patients at low risk, a decision to discontinue denosumab can be made after 5 years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover 3.

Risks Associated with Stopping Prolia Treatment

• Discontinuation of denosumab has been associated with an increased risk of multiple vertebral fractures, particularly in patients with a history of prolonged exposure to bisphosphonates 4.
• A study found that non-persistent denosumab users had a greater risk of osteoporotic fractures, vertebral fractures, and non-vertebral fractures compared to persistent denosumab users 5.
• Another study found that denosumab improved BMD significantly more than bisphosphonate treatment at 12 and 24 months, but only one study demonstrated greater osteoporotic fracture reduction with denosumab treatment 6.

Alternative Treatments

• Bisphosphonates may be considered as an alternative treatment for patients who are discontinuing denosumab, particularly for those at low risk of fracture 3.
• A study found that denosumab and zoledronate can reduce the risk of vertebral fractures in women with breast cancer undergoing treatment with aromatase inhibitors 7.
• The choice of alternative treatment should be based on individual patient factors, including bone health status, medical history, and risk of fracture.