From the Guidelines
Prolia (denosumab) can typically be used for up to 2 years, with continuation beyond 2 years based on clinical judgement, as recommended by the NCCN Guidelines for MM 1. The optimal duration of treatment remains somewhat individualized based on your specific fracture risk. After 2 years, your doctor may consider a drug holiday or switching to another medication, particularly if you've responded well and your fracture risk has decreased. However, unlike bisphosphonates, Prolia's effects wear off quickly after stopping (within 6-12 months), so discontinuation requires careful planning to avoid rebound bone loss. Prolia is administered as a 60mg subcutaneous injection every 6 months, and requires adequate calcium and vitamin D supplementation throughout treatment. Regular monitoring with bone density tests (typically every 1-2 years) and periodic assessment of kidney function and calcium levels helps guide long-term treatment decisions. The benefits of continued treatment must be weighed against potential risks like atypical fractures or osteonecrosis of the jaw, which increase slightly with longer duration of use. Some key points to consider when using Prolia include:
- The NCCN Guidelines for MM recommend bisphosphonates (category 1) or denosumab for all patients receiving therapy for symptomatic MM regardless of documented bone disease 1.
- Denosumab is preferred by the NCCN MM Panel in patients with renal disease 1.
- A baseline dental examination and monitoring for ONJ in all patients receiving a bone-modifying agent and monitoring for renal dysfunction with use of bisphosphonate therapy are recommended 1. It's essential to follow the guidelines and consult with your doctor to determine the best course of treatment for your specific condition.
From the Research
Duration of Prolia Treatment
The optimal duration of Prolia (denosumab) treatment for osteoporosis is a topic of ongoing research and debate. According to a systematic review and position statement by the European Calcified Tissue Society (ECTS) 2, a re-evaluation should be performed after 5 years of denosumab treatment.
Recommendations for Treatment Duration
- Patients considered at high fracture risk should either continue denosumab therapy for up to 10 years or be switched to an alternative treatment 2.
- 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 2.
- However, since the optimal bisphosphonate regimen post-denosumab is currently unknown, continuation of denosumab can also be considered until results from ongoing trials become available 2.
Risks of Discontinuation
Discontinuation of denosumab may lead to an increased risk of multiple vertebral fractures, and clinicians and patients should be aware of this potential risk 2.
- Data from phase 2 and 3 clinical trials underscore a rapid decrease of bone mineral density (BMD) and a steep increase in bone turnover markers (BTMs) after discontinuation of denosumab 2.
- Clinical case series report multiple vertebral fractures after discontinuation of denosumab, and a renewed analysis of FREEDOM and FREEDOM Extension Trial suggests that the risk of multiple vertebral fractures may be increased when denosumab is stopped due to a rebound increase in bone resorption 2.
Comparison with Other Treatments
Other studies have compared the effectiveness of denosumab with bisphosphonates, selective estrogen receptor modulators (SERMs), and placebo for the treatment of osteoporosis in postmenopausal women and cancer patients receiving endocrine therapy 3, 4, 5, 6.