What is Prolia Used For?
Prolia (denosumab) is a RANK ligand inhibitor used to treat osteoporosis and prevent fractures in postmenopausal women and men at high risk for fracture, as well as to increase bone mass in patients with glucocorticoid-induced osteoporosis, men receiving androgen deprivation therapy for prostate cancer, and women receiving aromatase inhibitor therapy for breast cancer. 1
FDA-Approved Indications
Prolia is specifically indicated for:
- Postmenopausal women with osteoporosis at high risk for fracture 1
- Men with osteoporosis at high risk for fracture to increase bone mass 1
- Glucocorticoid-induced osteoporosis in men and women at high risk for fracture (patients taking corticosteroid medicines such as prednisone for at least 6 months) 1
- Men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass and reduce fracture risk 1
- Women receiving adjuvant aromatase inhibitor therapy for breast cancer to increase bone mass and reduce fracture risk 1
Mechanism of Action and Clinical Effects
Denosumab is a fully human monoclonal antibody that binds to RANK ligand (RANKL), preventing it from activating RANK receptors on osteoclasts, thereby inhibiting osteoclast formation, function, and survival, which reduces bone resorption 2, 3, 4. This mechanism results in:
- Increased bone mineral density at the spine, hip, and femoral neck 2, 5
- Reduced bone turnover markers rapidly and sustainably 3, 5
- Significant fracture risk reduction including vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis 2, 5
Position in Treatment Guidelines
Denosumab is recommended as second-line pharmacologic treatment after bisphosphonates for both postmenopausal women and men with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates 6. Bisphosphonates (alendronate, risedronate, or zoledronate) remain first-line therapy due to their favorable balance of benefits, harms, and cost 6.
However, denosumab may be appropriate as initial therapy in:
- Patients at very high fracture risk 7
- Older patients who have difficulty with oral bisphosphonate dosing requirements (must take with full glass of water, remain upright for 30 minutes, avoid food/drink during this period) 7
- Patients with renal impairment (creatinine clearance <60 ml/min), as denosumab does not require dose adjustment for kidney function 8
- Patients intolerant of, unresponsive to, or with contraindications to bisphosphonates 7
Administration and Dosing
Prolia is administered as 60 mg subcutaneously every 6 months by a healthcare professional 1, 3. This convenient dosing schedule may improve adherence compared to daily or weekly oral bisphosphonates 2, 5.
Critical Safety Considerations and Contraindications
Do not use Prolia if:
- Blood calcium level is too low (hypocalcemia must be corrected before starting treatment) 1
- Patient is pregnant or planning to become pregnant (may harm unborn baby; effective contraception required during treatment and for 5 months after last dose) 1
- Patient is allergic to denosumab 1
All patients must receive adequate calcium and vitamin D supplementation as directed by their doctor while receiving Prolia 1.
Important Warnings
Rebound vertebral fractures: The most critical safety concern is the increased risk of multiple vertebral fractures after stopping, skipping, or delaying Prolia 1, 7. Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months to suppress rebound osteolysis 8.
Osteonecrosis of the jaw (ONJ): Patients should have dental examination before starting Prolia, complete any necessary dental work beforehand, and practice good oral hygiene during treatment 1. The risk of ONJ is approximately 5% with denosumab in some studies, though much lower (<1%) in osteoporosis dosing 6.
Serious infections: Denosumab may affect the body's ability to fight infections, including skin infections (cellulitis), abdominal infections, bladder infections, ear infections, and endocarditis 1, 3. Patients with weakened immune systems have increased infection risk 1.
Atypical femoral fractures: Unusual thigh bone fractures can occur, presenting as new or unusual pain in hip, groin, or thigh 1.
What Denosumab is NOT Used For
Denosumab is NOT recommended as adjuvant therapy to reduce breast cancer recurrence 6. While the ABCSG-18 trial showed some benefit with lower-dose denosumab (60 mg every 6 months), the larger D-CARE trial using higher-dose denosumab (120 mg monthly initially, then every 12 weeks) showed no improvement in bone metastasis-free survival and unacceptably high ONJ risk (5% vs <1% with placebo) 6. Given inconsistent results and significant toxicity at higher doses, guidelines do not endorse denosumab for cancer recurrence prevention 6.