From the Guidelines
Managing Prolia (denosumab) withdrawal requires careful medical supervision to prevent rebound bone loss and increased fracture risk, and the most effective strategy is to switch to a bisphosphonate, such as alendronate, risedronate, or zoledronic acid, within 1-3 months of the last Prolia injection, as recommended by the European Calcified Tissue Society 1. When discontinuing denosumab, it is crucial to be aware of the potential for rebound increased bone turnover, which can lead to severe hypercalcemia and a marked increase in vertebral fracture risk 1. To mitigate this risk, the following steps should be taken:
- Work closely with your healthcare provider to develop a transition plan
- Switch to another osteoporosis medication like a bisphosphonate within 1-3 months of your last Prolia injection
- Consider calcium supplements (1000-1200 mg daily) and vitamin D (800-1000 IU daily) during this transition period, as suggested by general osteoporosis management guidelines 1
- Regular bone density monitoring through DEXA scans is essential to track your bone health
- Report any new back pain promptly, as this could indicate vertebral fractures which can occur during withdrawal The choice of bisphosphonate may depend on various factors, including the patient's specific needs and medical history, but options like alendronate (70 mg once per week), risedronate (35 mg once per week), and zoledronic acid (5 mg administered once per year by IV infusion) have been shown to be effective in preventing bone loss and decreasing bone turnover 1. It is also important to note that teriparatide, an anabolic hormonal therapy, is not a suitable option for cancer patients due to its potential risks and limitations 1. Ultimately, a structured transition plan, guided by the most recent and highest quality evidence, is crucial to ensure the best possible outcomes for patients discontinuing denosumab.
From the Research
Managing Prolia Withdrawal
To manage Prolia (denosumab) withdrawal, it is essential to consider the potential risks and benefits of discontinuing treatment.
- The risk of multiple vertebral fractures after discontinuation of denosumab has been reported in several studies 2, 3.
- A systematic review by the European Calcified Tissue Society (ECTS) found that denosumab discontinuation may lead to a rapid decrease in bone mineral density (BMD) and a steep increase in bone turnover markers (BTMs) 3.
- The optimal strategy for managing Prolia withdrawal is not well established, but several options are available:
- Continuing denosumab therapy for up to 10 years for patients at high fracture risk 3.
- Switching to an alternative treatment, such as bisphosphonates, to reduce or prevent the rebound increase in bone turnover 3.
- Discontinuing denosumab after 5 years for patients at low risk, but considering bisphosphonate therapy to reduce or prevent the rebound increase in bone turnover 3.
Considerations for Prolia Withdrawal
When considering Prolia withdrawal, several factors should be taken into account:
- The patient's fracture risk: Patients at high fracture risk may require continued denosumab therapy or alternative treatment to prevent fractures 3.
- The duration of denosumab treatment: A re-evaluation should be performed after 5 years of denosumab treatment to determine the best course of action 3.
- The potential for rebound increase in bone turnover: Bisphosphonate therapy may be considered to reduce or prevent this increase 3.
- The lack of strong evidence for measures to prevent bone loss after denosumab discontinuation: Clinicians and patients should be aware of the potential risks and benefits of Prolia withdrawal 3.
Alternative Treatments
Alternative treatments, such as bisphosphonates, may be considered for patients discontinuing denosumab: