What is the indication for Prolia (Denosumab)?

From the Guidelines

Prolia (denosumab) is a recommended treatment option for osteoporosis in postmenopausal women and men at high risk for fractures, with a standard dose of 60 mg administered as a subcutaneous injection once every 6 months, as supported by high-quality evidence from recent studies 1.

Key Points

• Prolia works by inhibiting RANK ligand, a protein that activates osteoclasts (cells that break down bone), thereby decreasing bone resorption and increasing bone density.
• Patients taking Prolia should also take calcium (1000 mg daily) and vitamin D (at least 400 IU daily) supplements to support bone health, as recommended by recent guidelines 1.
• Common side effects include back pain, pain in extremities, musculoskeletal pain, high cholesterol, and urinary tract infections.
• Rare but serious side effects include osteonecrosis of the jaw and atypical femur fractures, and patients should maintain good dental hygiene and report any new thigh or groin pain.

Treatment Considerations

• Denosumab is a preferred option for patients with castration-resistant prostate cancer (CRPC) and bone metastases, as it has been shown to delay the time to first skeletal-related event compared to zoledronic acid 1.
• The optimal duration of denosumab treatment remains unclear, but it is recommended to continue treatment until there is a significant change in the patient's condition or until treatment is no longer tolerated.
• Patients with impaired renal function should be monitored closely for hypocalcemia and hypophosphatemia, and the dose and schedule of denosumab may need to be adjusted accordingly.

Monitoring and Prevention

• Patients should have a dental evaluation and complete any necessary invasive dental treatments before initiating denosumab treatment, as recommended by recent guidelines 1.
• Correction of vitamin D deficiency and vitamin D supplementation with adequate intake of calcium are recommended to maintain normal serum calcium levels.
• Patients should be monitored regularly for signs and symptoms of osteonecrosis of the jaw and atypical femur fractures, and should report any new thigh or groin pain promptly.

From the FDA Drug Label

INDICATIONS AND USAGE Prolia is a RANK ligand (RANKL) inhibitor indicated for treatment: of postmenopausal women with osteoporosis at high risk for fracture (1.1) to increase bone mass in men with osteoporosis at high risk for fracture (1.2) of glucocorticoid-induced osteoporosis in men and women at high risk for fracture (1.3) to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer (1.4) to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer (1.5)

Prolia treats various conditions, including:

• Postmenopausal osteoporosis in women at high risk for fracture
• Osteoporosis in men at high risk for fracture
• Glucocorticoid-induced osteoporosis in men and women at high risk for fracture
• Increases bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increases bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer 2 2

From the Research

Overview of Prolia

• Prolia, also known as denosumab, is a human monoclonal antibody used to treat postmenopausal osteoporosis in women at increased or high risk of fractures 3, 4, 5.
• It works by targeting the key bone resorption mediator RANKL, inhibiting osteoclast formation, function, and survival, thereby reducing bone resorption 3, 4, 5.

Efficacy of Prolia

• Denosumab has been shown to reduce the risk of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis 3, 4, 5, 6.
• It increases bone mineral density (BMD) at all skeletal sites, including the lumbar spine and total hip, compared to placebo or bisphosphonates 3, 4, 5, 7.
• Denosumab has been found to be more effective in improving BMD than bisphosphonates, including in women switched from a bisphosphonate regimen 3, 4, 5, 7.

Safety and Tolerability of Prolia

• Denosumab is generally well tolerated, with a safety profile consistent with that observed in clinical trials 3, 4, 5, 6.
• However, there is an increased risk of multiple vertebral fractures after discontinuation of the drug, which requires consideration of subsequent management options 3, 6.
• Initial safety concerns, such as infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures, have been largely alleviated by further study and experience 6.

Comparison with Other Treatments

• Denosumab has been compared to zoledronic acid (ZOL) in postmenopausal women with osteoporosis previously treated with oral bisphosphonates, and was found to be associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling 7.
• Denosumab may be an appropriate initial therapy in patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, as well as patients who are intolerant of, unresponsive to, or have contraindications to other therapies 6.