Should Prolia (denosumab) be discontinued with improved Dual-Energy X-ray Absorptiometry (DEXA) results?

From the Guidelines

Discontinuing Prolia (denosumab) solely based on improved DEXA scan results is not recommended due to the potential for a rebound effect with accelerated bone loss and increased fracture risk. The decision to discontinue Prolia should be made under careful physician supervision, considering the patient's specific fracture risk factors, the degree of improvement in bone density, potential side effects, and long-term bone health goals. According to a review published in the Annals of Oncology in 2019 1, after drug discontinuation, denosumab's effect on bone turnover is rapidly reversible, which can lead to severe hypercalcemia and a marked increase in vertebral fracture risk.

To mitigate this risk, a transition plan to another osteoporosis medication, typically a bisphosphonate, should be considered. The European Calcified Tissue Society recommends a re-evaluation after 5 years of denosumab treatment, and bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover 1. Key factors to consider when deciding whether to discontinue Prolia include:

• The patient's overall bone health and fracture risk
• The degree of improvement in bone density as shown by DEXA scan results
• Potential side effects of continued denosumab treatment
• The availability and suitability of alternative osteoporosis therapies, such as bisphosphonates

It is essential to weigh these factors and discuss them with a healthcare provider to make an informed decision about discontinuing Prolia, rather than relying solely on improved DEXA scan results.

From the FDA Drug Label

5.6 Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia Treatment 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 should be based on an individual benefit-risk assessment. Although improved DEXA results may indicate a reduced risk of fractures, the risk of multiple vertebral fractures increases after discontinuation of Prolia treatment.

• Key considerations:
  • Fracture risk increases after discontinuation of Prolia.
  • Patients should be transitioned to an alternative antiresorptive therapy if Prolia is discontinued.
  • Individual benefit-risk assessment is necessary before making a decision. Based on the information provided, it is not possible to make a definitive recommendation to discontinue Prolia solely based on improved DEXA results. A thorough evaluation of the patient's overall condition and benefit-risk profile is necessary to make an informed decision 2.

From the Research

Discontinuation of Prolia with Improved DEXA Results

• The decision to discontinue Prolia (denosumab) with improved DEXA results should be based on individual patient factors and the risk of fracture 3, 4.
• Studies have shown that denosumab increases bone mineral density (BMD) more than bisphosphonates at 12 and 24 months 4, 5.
• However, discontinuation of denosumab can lead to a rapid reversal of its effects on bone markers and BMD, and increase the risk of fractures 3.
• It is recommended that denosumab not be discontinued without starting another treatment, such as bisphosphonates, to maintain bone health 3.
• The choice to discontinue denosumab should be made on a case-by-case basis, taking into account the patient's fracture risk, BMD, and other individual factors 3, 6, 5.
• There is limited data on the long-term effects of discontinuing denosumab, and further studies are needed to determine the optimal treatment strategy 4, 7.

Considerations for Discontinuation

• Patients with improved DEXA results may still be at risk for fractures, and discontinuation of denosumab should be approached with caution 3, 4.
• The risk of adverse events, such as osteonecrosis of the jaw and atypical femoral fractures, should be considered when deciding to discontinue denosumab 3, 6.
• The patient's renal function and other comorbidities should also be taken into account when making the decision to discontinue denosumab 3, 7.
• A thorough evaluation of the patient's individual factors and risk profile should be conducted before discontinuing denosumab 3, 4, 6, 5, 7.