When should Prolia (denosumab) be discontinued in patients with osteoporosis?

From the Guidelines

Prolia (denosumab) should not be discontinued after 3 years of use without careful consideration and planning for alternative therapy, as abrupt discontinuation can lead to rapid bone loss and increased fracture risk. When discontinuation is necessary, patients should transition to another antiresorptive medication, typically an oral or IV bisphosphonate like alendronate or zoledronic acid, to reduce the risk of rebound osteolysis and vertebral fractures 1. The decision to discontinue Prolia should be individualized and based on baseline risk for fractures, type of medication, duration of treatment, and benefits and harms of discontinuation 1.

Some key considerations for discontinuing Prolia include:

• The risk of rebound osteolysis and vertebral fractures after discontinuation, which can be mitigated by transitioning to a bisphosphonate therapy 1
• The duration of treatment, with discontinuation considered after 5-10 years of therapy in lower-risk patients, but high-risk patients may benefit from continued treatment or switching to another agent 1
• The importance of individualized treatment selection based on comorbidities, concomitant medications, and risk for falls and fractures 1

In general, discontinuation of Prolia without follow-up therapy is not recommended, and patients should be closely monitored for signs of rebound osteolysis and vertebral fractures after discontinuation 1. Patients with hypocalcemia, hypersensitivity to denosumab, or those who develop osteonecrosis of the jaw or atypical femur fractures should also discontinue Prolia with appropriate alternative management. According to the most recent guideline, the American College of Physicians recommends that clinicians consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation 1.

From the FDA Drug Label

Following discontinuation of Prolia treatment, fracture risk increases, including the risk of multiple vertebral fractures Treatment with Prolia results in significant suppression of bone turnover and cessation of Prolia treatment results in increased bone turnover above pretreatment values 9 months after the last dose of Prolia. Bone turnover then returns to pretreatment values 24 months after the last dose of Prolia In addition, bone mineral density (BMD) returns to pretreatment values within 18 months after the last injection If Prolia treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy

Discontinuation of Prolia is not explicitly stated to occur after a specific duration of use, such as 3 years. The decision to discontinue Prolia should be based on an individual benefit-risk assessment. Patients should be transitioned to an alternative antiresorptive therapy if Prolia is discontinued 2.

From the Research

Discontinuation of Prolia (Denosumab) in Patients with Osteoporosis

• Prolia (denosumab) is a human monoclonal antibody used to treat osteoporosis in postmenopausal women at increased or high risk of fracture 3.
• The decision to discontinue denosumab should be based on individual patient factors, as there is no specific recommendation to discontinue the drug after a certain period, such as 3 years 4, 5.
• Discontinuation of denosumab can lead to a rebound effect, characterized by an increase in bone turnover markers and a loss of accrued bone mineral density, which may increase the risk of fractures, particularly multiple vertebral fractures 4, 6.
• The optimal duration of denosumab treatment and the best approach for discontinuation are not well established, and further research is needed to address these questions 5, 6.
• In general, denosumab can be continued indefinitely in patients who are experiencing benefits from the treatment and are not experiencing adverse effects 4.
• However, discontinuation may be considered in patients who have achieved a significant increase in bone mineral density, have a low risk of fracture, or are experiencing adverse effects 4, 7.

Factors to Consider When Discontinuing Denosumab

• The risk of multiple vertebral fractures after discontinuation of denosumab should be considered, particularly in patients with a history of vertebral fractures or those who have been treated with denosumab for an extended period 4, 6.
• The use of sequential osteoporosis therapy after denosumab discontinuation may be considered to reduce the risk of multiple vertebral fractures 4, 6.
• Patient factors, such as age, bone mineral density, and fracture risk, should be taken into account when deciding whether to discontinue denosumab 5, 7.