Should denosumab (Prolia) be discontinued upon resolution of osteoporosis?

From the Guidelines

Prolia (denosumab) should not be automatically discontinued when osteoporosis appears to resolve, as discontinuation can lead to a rebound effect with rapid bone mineral density loss and increased fracture risk within 12 months of stopping treatment. Discontinuation of Prolia requires careful consideration, and if being considered after achieving good bone density results, patients should transition to an alternative osteoporosis medication, typically a bisphosphonate like alendronate, to maintain bone protection 1. This transition should occur at the time the next Prolia dose would be due. The decision to discontinue should be made by a healthcare provider based on individual fracture risk assessment, duration of treatment (typically at least 5-10 years), and bone mineral density measurements.

Some key points to consider when deciding whether to discontinue Prolia include:

• The risk of rebound increased bone turnover and associated vertebral fracture risk after stopping denosumab 1
• The potential benefits of long-term continuation of Prolia for patients with high fracture risk, with periodic reassessment of benefits versus risks
• The importance of transitioning to an alternative osteoporosis medication, such as a bisphosphonate, to maintain bone protection if discontinuation is being considered

According to the European Calcified Tissue Society, 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. However, as the optimal bisphosphonate regimen post-denosumab is currently unknown, continuation of denosumab can also be considered until results from ongoing trials become available.

In terms of specific bisphosphonates, there is good evidence of benefit from treatment with several oral bisphosphonates, including alendronate (70 mg once per week), risedronate (35 mg once per week), and ibandronate (150 mg once per month) 1. These treatments prevent bone loss and decrease bone turnover, but the challenge is to maintain good adherence due to potential GI adverse effects.

Ultimately, the decision to discontinue Prolia should be made on a case-by-case basis, taking into account the individual patient's fracture risk, treatment duration, and bone mineral density measurements, as well as the potential risks and benefits of continued treatment versus transition to an alternative osteoporosis medication.

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 New vertebral fractures occurred as early as 7 months (on average 19 months) after the last dose of Prolia. Prior vertebral fracture was a predictor of multiple vertebral fractures after Prolia discontinuation. Evaluate an individual's benefit-risk before initiating treatment with Prolia If Prolia treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy

The decision to discontinue Prolia in patients with resolved osteoporosis should be based on an individual benefit-risk assessment.

• Key considerations include the increased risk of fractures after discontinuation of Prolia treatment, particularly multiple vertebral fractures.
• Patients should be transitioned to an alternative antiresorptive therapy if Prolia treatment is discontinued 2.
• The benefit-risk profile should be evaluated for each patient before making a decision to discontinue Prolia 2.

From the Research

Discontinuation of Prolia with Osteoporosis Resolution

• The decision to discontinue Prolia (denosumab) in patients with resolved osteoporosis should be based on individual patient factors and risk assessment 3.
• Studies suggest that discontinuation of bisphosphonates, another class of osteoporosis medications, can be considered in many patients, although high-risk patients may benefit from continued therapy 4, 5.
• Denosumab, however, has a pronounced loss of anti-resorptive effect after discontinuation, which can result in rebound vertebral fractures 6.
• There is limited data on the optimal duration of Prolia treatment and the effects of discontinuation, but sequential treatment regimens are being explored to minimize long-term safety issues 7.
• Clinicians should consider the individual patient's risk factors, bone density, and fracture history when deciding whether to discontinue Prolia or switch to another treatment 4, 6, 7.
• It is essential to weigh the benefits and risks of continued treatment with Prolia, considering the potential for atypical femoral fractures and other long-term safety issues 6, 7.