From the Guidelines
Prolia (denosumab) treatment should be continued for up to 2 years, with the option to extend beyond 2 years based on clinical judgement, as recommended by the NCCN Guidelines for MM 1. The decision to continue or discontinue Prolia treatment should be individualized based on fracture risk, bone mineral density measurements, and response to therapy, with periodic reassessment by a healthcare provider. Some key points to consider when determining the duration of Prolia treatment include:
- The bone-protective effects of Prolia diminish rapidly after discontinuation, and stopping the medication without transitioning to another osteoporosis medication can lead to a rebound effect with accelerated bone loss and increased fracture risk within 12-18 months after the last dose 1.
- The NCCN Guidelines for MM recommend continuing bone-targeting treatment (bisphosphonates or denosumab) for up to 2 years, with the option to extend beyond 2 years based on clinical judgement 1.
- The frequency of dosing (monthly vs every 3 months) should be determined based on individual patient criteria and response to therapy 1.
- Patients should be monitored regularly for serum calcium and vitamin D levels, and hypocalcemia is an adverse effect of all bone resorptive agents, including denosumab 1.
- Osteonecrosis of the jaw (ONJ) is an uncommon but potentially serious complication of intravenous bisphosphonates and denosumab, and patients should receive a comprehensive dental examination and appropriate preventive dentistry before bone-modifying therapy 1.
From the FDA Drug Label
The risk of ONJ may increase with duration of exposure to Prolia 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.
The duration of Prolia treatment is not explicitly stated in the drug label. However, it is mentioned that the risk of ONJ may increase with duration of exposure to Prolia. Additionally, after cessation of Prolia treatment, bone turnover returns to pretreatment values within 24 months and BMD returns to pretreatment values within 18 months. It is recommended to transition to an alternative antiresorptive therapy if Prolia treatment is discontinued 2.
From the Research
Duration of Prolia Treatment
- The duration of Prolia (denosumab) treatment varies depending on the indication and patient response.
- For postmenopausal women with osteoporosis, denosumab has been shown to be effective for up to 10 years of therapy, with benefits maintained in reducing the risk of vertebral, nonvertebral, and hip fractures and increasing bone mineral density (BMD) across skeletal sites 3.
- In the treatment of giant cell tumor of bone (GCTB), the optimal treatment duration with denosumab is unclear, and long-term treatment is associated with adverse events like osteonecrosis of the jaw (ONJ) and atypical femoral fractures 4.
- A study of denosumab-treated GCTB patients found that the duration of treatment varied from 2.5 to 13 months, with a mean of 5.9 months 5.
- The use of denosumab in the neoadjuvant setting for GCTB has been shown to be effective in downsizing tumors and facilitating less morbid surgery, but the optimal duration of treatment in this setting is still being investigated 6.
- Denosumab was approved by the FDA in 2013 for the treatment of patients with GCTB that is unresectable or when surgery is likely to result in severe morbidity, with ongoing questions regarding optimal scheduling, patient selection, and long-term toxicity concerns 7.