What is the use of Prolia (denosumab) medication?

From the Guidelines

Prolia (denosumab) is a prescription medication used to treat osteoporosis in postmenopausal women at high risk for fractures and to increase bone mass in men with osteoporosis, as well as to prevent or delay disease-associated skeletal-related events (SREs) in patients with bone metastases from cancer, such as prostate cancer or breast cancer. The standard dose is 60 mg administered as a subcutaneous injection once every 6 months by a healthcare professional, or every 4 weeks for patients with cancer and bone metastases 1. Patients taking Prolia should also take calcium (1000 mg daily) and vitamin D (at least 400 IU daily) supplements to support bone health. Common side effects include back pain, arm/leg pain, high cholesterol, muscle pain, and bladder infections. Prolia works by blocking a protein called RANK ligand, which helps prevent the breakdown of bone and increases bone density. This mechanism differs from bisphosphonates, another class of osteoporosis medications. Before starting Prolia, patients should have their calcium levels checked, as hypocalcemia is a potential serious side effect. Patients should also maintain good dental health while on Prolia, as it carries a small risk of osteonecrosis of the jaw. The medication should not be stopped without consulting a healthcare provider, as there can be an increased risk of vertebral fractures after discontinuation. Some key points to consider when using Prolia include:

• Monitoring of creatinine clearance is required to guide dosing of zoledronic acid, but not denosumab 1
• Denosumab may be administered to patients with impaired renal function or even patients on hemodialysis, but with a higher risk for severe hypocalcemia and hypophosphatemia 1
• Oral hygiene, baseline dental evaluation for high-risk individuals, and avoidance of invasive dental surgery during therapy are recommended to reduce the risk of osteonecrosis of the jaw 1
• Supplemental calcium and vitamin D are recommended to prevent hypocalcemia in patients receiving either denosumab or zoledronic acid 1
• The optimal duration of zoledronic acid or denosumab in patients with cancer and bone metastases remains unclear, but a multi-institutional, open-label, randomized trial found that zoledronic acid every 12 weeks was noninferior to zoledronic acid every 4 weeks 1

From the FDA Drug Label

Prolia is a prescription medicine used to: Treat osteoporosis (thinning and weakening of bone) in women after menopause ("change of life") who: are at high risk for fracture (broken bone) cannot use another osteoporosis medicine or other osteoporosis medicines did not work well Increase bone mass in men with osteoporosis who are at high risk for fracture Treat osteoporosis in men and women who will be taking corticosteroid medicines (such as prednisone) for at least 6 months and are at high risk for fracture Treat bone loss in men who are at high risk for fracture receiving certain treatments for prostate cancer that has not spread to other parts of the body Treat bone loss in women who are at high risk for fracture receiving certain treatments for breast cancer that has not spread to other parts of the body

The use of Prolia (denosumab) medication is to treat osteoporosis and increase bone mass in men and women at high risk for fracture, as well as to treat bone loss in patients receiving certain cancer treatments. Key uses include:

• Treating osteoporosis in postmenopausal women and men at high risk for fracture
• Increasing bone mass in men with osteoporosis
• Treating glucocorticoid-induced osteoporosis
• Treating bone loss in patients with prostate or breast cancer 2 2

From the Research

Use of Prolia (Denosumab) Medication

The use of Prolia (denosumab) medication is primarily for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures 3, 4, 5, 6. Key points about its use include:

• Denosumab is a human monoclonal antibody that targets the key bone resorption mediator RANKL, inhibiting osteoclast formation, function, and survival 3, 4, 5.
• It is administered via subcutaneous injection once every 6 months 3, 4, 5, 6.
• Denosumab has been shown to reduce the risk of vertebral, nonvertebral, and hip fractures compared to placebo in postmenopausal women with osteoporosis 3, 4, 5, 6.
• It increases bone mineral density (BMD) across skeletal sites and decreases markers of bone turnover more than bisphosphonates in some cases 3, 4, 5, 6.
• Denosumab is generally well tolerated, although there are concerns about the potential for multiple vertebral fractures after discontinuation of the drug 3, 7.

Indications and Patient Groups

Denosumab is indicated for:

• Postmenopausal women with osteoporosis at increased or high risk of fractures 3, 4, 5, 6.
• Women who have failed or are intolerant to other osteoporosis treatments 6.
• It may also be used in the treatment of glucocorticoid-induced osteoporosis, and for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer 7.

Administration and Safety

• Denosumab is administered once every 6 months via subcutaneous injection 3, 4, 5, 6.
• Initial safety concerns included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures, but further study and experience have provided reassurance on these issues 7.
• There are anecdotal reports of an increased risk of multiple vertebral fractures following discontinuation of denosumab, highlighting the need for consideration of subsequent management options 3, 7.