What is the preferred treatment for patients with very high fracture risk, Evenity (romosozumab) or Prolia (denosumab), considering their anabolic and antiresorptive properties?

From the Guidelines

For patients with very high fracture risk, Evenity (romosozumab) is generally the preferred initial treatment over Prolia (denosumab) due to its anabolic properties, which allow for increased bone formation and decreased bone resorption, making it particularly effective for rapidly reducing fracture risk in high-risk patients. This recommendation is based on the latest guidelines from the American College of Rheumatology, which suggest that anabolic agents, such as Evenity, are conditionally recommended over antiresorptive agents, such as Prolia, for adults with very high fracture risk 1.

The preferred treatment approach for patients with very high fracture risk involves a 12-month course of Evenity, administered as two consecutive subcutaneous injections once monthly, followed by transition to an antiresorptive agent like Prolia to maintain bone gains. Key points to consider when making this decision include:

• Evenity's dual action, which both increases bone formation and decreases bone resorption, making it effective for rapidly reducing fracture risk in high-risk patients.
• The importance of transitioning to an antiresorptive agent after completing the 12-month Evenity course to prevent rebound bone loss and vertebral fractures.
• The need for shared decision-making with patients to ensure they understand the potential benefits and harms of each treatment option, including the need for sequential therapy after Evenity or Prolia.
• The consideration of patient-specific comorbidities and preferences when selecting an osteoporosis therapy.

It is essential to note that Evenity is contraindicated in patients with a history of myocardial infarction or stroke within the past year due to cardiovascular concerns, and its use should be carefully considered in patients with other comorbidities or risk factors 1. Overall, the choice of therapy should be based on a comprehensive assessment of the patient's fracture risk, medical history, and individual preferences, with the goal of minimizing the risk of fractures and related morbidity and mortality.

From the FDA Drug Label

The anabolic effect of EVENITY wanes after 12 monthly doses of therapy. EVENITY is indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. EVENITY significantly reduced the incidence of new vertebral fractures through month 12 compared to placebo In addition, the significant reduction in fracture risk persisted through the second year in women who received EVENITY during the first year and transitioned to denosumab compared to those who transitioned from placebo to denosumab

Evenity (romosozumab) is an anabolic agent, which means it helps to build bone, whereas Prolia (denosumab) is an antiresorptive agent, which means it helps to prevent bone breakdown.

• Key differences:
  • Evenity has a dual effect on bone metabolism, both increasing bone formation and decreasing bone resorption.
  • Prolia only decreases bone resorption.
• Clinical implications:
  • Evenity may be more effective in patients with very high fracture risk due to its anabolic properties.
  • The study shows that Evenity significantly reduced the incidence of new vertebral fractures compared to placebo, and this reduction persisted even after transitioning to denosumab.
  • However, it is essential to consider the limitations of use for Evenity, as its anabolic effect wanes after 12 monthly doses, and continued therapy with an anti-resorptive agent should be considered if osteoporosis therapy remains warranted 2.

From the Research

Comparison of Evenity and Prolia for High Fracture Risk

• Evenity (romosozumab) and Prolia (denosumab) are two treatments for osteoporosis, but they have different mechanisms of action. Evenity is an anabolic agent that increases bone formation and decreases bone resorption, while Prolia is an antiresorptive agent that only decreases bone resorption 3, 4.
• Studies have shown that Evenity has a dual effect on bone, increasing bone formation and decreasing bone resorption, making it a more effective treatment for patients with very high fracture risk 3, 4, 5.
• In contrast, Prolia only decreases bone resorption, which may not be enough to significantly increase bone mineral density and reduce fracture risk in patients with very high fracture risk 5.
• Clinical studies have demonstrated that Evenity can increase bone mineral density and reduce the risk of vertebral fractures in patients with osteoporosis at high risk of fracture 3, 6.
• Additionally, studies have shown that Evenity followed by denosumab (Prolia) can lead to a higher increase in bone mineral density and a greater reduction in fragility fractures compared to other treatments 5.

Anabolic vs Antiresorptive Properties

• The anabolic properties of Evenity make it a more attractive option for patients with very high fracture risk, as it can help to rebuild bone and increase bone strength 3, 4.
• In contrast, antiresorptive agents like Prolia can only help to maintain existing bone density, which may not be enough to significantly reduce fracture risk in patients with very high fracture risk 5.
• The dual effect of Evenity on bone formation and resorption makes it a more effective treatment for patients with osteoporosis at high risk of fracture, and its use is recommended as a first-line treatment in patients with recent major fractures 4, 5.