From the Guidelines
Xgeva (denosumab) is not approved for treating osteoporosis, and patients with osteoporosis should be treated with Prolia or other osteoporosis medications rather than Xgeva. The main difference between Xgeva and Prolia is the dosing regimen and approved indications, despite containing the same active ingredient. Prolia is specifically approved for the treatment of osteoporosis, with a lower dose of 60 mg every 6 months, whereas Xgeva is approved for preventing skeletal-related events in patients with bone metastases from solid tumors, treating giant cell tumor of bone, and managing hypercalcemia of malignancy, with a higher dose of 120 mg every 4 weeks 1.
Key Points to Consider
- The American College of Physicians recommends offering pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women with known osteoporosis, with high-quality evidence supporting this recommendation 1.
- Denosumab has been shown to reduce radiographic vertebral, nonvertebral, and hip fractures compared with placebo in postmenopausal osteoporotic women, with a significant decrease in incident radiographic vertebral fractures, nonvertebral fractures, and hip fractures 1.
- The FREEDOM trial demonstrated a statistically significant difference in new radiographic vertebral fractures, nonvertebral fractures, and hip fractures between denosumab and placebo, with denosumab reducing the risk of these fractures 1.
- It is essential to note that while denosumab is effective in treating osteoporosis, Xgeva is not approved for this indication, and patients should be treated with Prolia or other osteoporosis medications rather than Xgeva.
Clinical Implications
- Clinicians should offer pharmacologic treatment with approved medications, such as Prolia, to reduce the risk of fractures in patients with osteoporosis.
- The choice of medication should be based on patient preferences, fracture risk profile, and benefits, harms, and costs of medications.
- Clinicians should be aware of the different dosing regimens and approved indications for denosumab, and prescribe the appropriate formulation and dose for the specific clinical scenario.
From the Research
Xgeva (Denosumab) in Osteoporosis Treatment
- Xgeva (denosumab) is a fully human monoclonal antibody used to treat osteoporosis by inhibiting osteoclastic bone resorption 2, 3, 4, 5.
- It is approved for the treatment of postmenopausal women and men with osteoporosis, as well as for women and men with glucocorticoid-induced osteoporosis who are at high risk for fracture 2.
- Denosumab has been shown to increase bone mineral density, reduce bone turnover markers, and reduce the risk of vertebral, hip, and nonvertebral fractures in postmenopausal women with osteoporosis 2, 3, 4, 5.
- The recommended dose of denosumab is 60 mg subcutaneously every 6 months 2, 3, 4, 5.
- Common side effects of denosumab include atypical femur fractures and osteonecrosis of the jaw, and discontinuation of denosumab can lead to rapidly rising bone turnover markers and decreasing bone density 2, 5.
Efficacy in Specific Patient Populations
- Denosumab has been shown to be effective in postmenopausal women with osteoporosis, increasing bone mineral density and reducing fracture risk 2, 3, 4, 5.
- It has also been shown to be effective in men with osteoporosis, including those with prostate cancer receiving androgen deprivation therapy 4, 5.
- Denosumab has been shown to improve bone mineral density and microarchitecture, and reduce bone pain in women with osteoporosis with and without glucocorticoid treatment 6.
Safety Considerations
- Denosumab has a generally favorable safety profile, but can cause serious side effects such as atypical femur fractures and osteonecrosis of the jaw 2, 5.
- Discontinuation of denosumab can lead to rapidly rising bone turnover markers and decreasing bone density, and patients should be switched to another antiresorptive agent to maintain the benefit achieved with denosumab 2.