What is the recommended duration of treatment with Prolia (denosumab) for osteoporosis?

From the Guidelines

The recommended duration of treatment with Prolia (denosumab) for osteoporosis is typically long-term, with most patients continuing therapy for at least 5-10 years. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of long-term treatment to prevent fractures and maintain bone density 1.

Key Considerations

• Treatment should not be abruptly discontinued due to the risk of rapid bone loss and increased fracture risk that can occur when the medication is stopped.
• Prolia is administered as a 60 mg subcutaneous injection every 6 months, and patients should maintain adequate calcium and vitamin D intake throughout treatment.
• For patients who need to discontinue Prolia, transition to an alternative osteoporosis medication (typically a bisphosphonate) is recommended to prevent the rebound bone loss, as suggested by recent guidelines 1.
• Regular monitoring of bone mineral density every 1-2 years during treatment is advised to assess effectiveness.

Rationale

The long-term approach is justified because osteoporosis is a chronic condition, and denosumab works by inhibiting bone resorption through blocking RANK ligand, but this effect is reversible when the drug is discontinued, necessitating either continued treatment or appropriate transition to alternative therapy. Recent studies and guidelines support the use of denosumab as a viable option for the treatment of osteoporosis, especially in patients at high risk of fracture 1.

Important Notes

• The decision to treat osteoporotic patients with denosumab should be based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications.
• Sequential osteoporosis treatment is recommended to prevent rebound bone loss and vertebral fractures after discontinuation of denosumab, romosozumab, and parathyroid hormone-related protein analogs 1.

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 recommended duration of treatment with Prolia is not explicitly stated in the provided drug labels. However, it is mentioned that fracture risk increases after discontinuation of Prolia treatment, and patients should be transitioned to an alternative antiresorptive therapy if Prolia treatment is discontinued.

• The decision to continue or discontinue Prolia treatment should be based on an individual benefit-risk assessment.
• Patients with a history of vertebral fractures are at a higher risk of developing multiple vertebral fractures after discontinuing Prolia treatment.
• Bone turnover and bone mineral density return to pretreatment values within 9-24 months after the last dose of Prolia.
• The risk of atypical femoral fractures may increase with the duration of exposure to Prolia 2. It is essential to weigh the benefits and risks of continuing Prolia treatment against alternative therapies, considering individual patient factors and medical history.

From the Research

Recommended Duration of Treatment with Prolia (Denosumab)

The recommended duration of treatment with Prolia (denosumab) for osteoporosis is not strictly defined, but several studies provide insight into the efficacy and safety of long-term treatment.

• Treatment with denosumab has been shown to be effective in reducing the risk of vertebral, nonvertebral, and hip fractures, and increasing bone mineral density (BMD) over up to 10 years of therapy 3.
• The FREEDOM trial and its 7-year open-label extension demonstrated that the benefits of denosumab treatment were maintained over up to 10 years, with no significant increase in adverse events 3.
• Another study found that denosumab treatment increased BMD and reduced markers of bone turnover over 12 months, with similar effects observed in patients who had previously received antiosteoporotic therapy and those who had not 4.
• The optimal duration of treatment with denosumab has not been established, but it is generally recommended to continue treatment for as long as the patient is at risk of fracture and the benefits of treatment outweigh the potential risks 5, 6, 7.

Considerations for Long-Term Treatment

When considering long-term treatment with denosumab, several factors should be taken into account, including:

• The patient's individual risk of fracture and the potential benefits of treatment
• The patient's medical history and any potential contraindications to treatment
• The potential risks of long-term treatment, including the risk of multiple vertebral fractures after discontinuation of the drug 3, 5
• The need for regular monitoring of BMD and bone turnover markers to assess the effectiveness of treatment and potential adverse effects 4, 6, 7