What is the recommended use and dosage of Denosumab (Prolia) for treating osteoporosis and bone metastases?

Denosumab (Prolia) for Osteoporosis and Bone Metastases

Recommended Dosing by Indication

For osteoporosis, administer denosumab 60 mg subcutaneously every 6 months; for bone metastases from solid tumors, administer 120 mg subcutaneously every 4 weeks. 1, 2

Osteoporosis Dosing

• 60 mg subcutaneous injection every 6 months for postmenopausal osteoporosis, male osteoporosis, glucocorticoid-induced osteoporosis, and cancer treatment-induced bone loss 1, 3
• Administer in the upper arm, upper thigh, or abdomen 1
• If a dose is missed, administer as soon as possible and schedule subsequent doses every 6 months from that injection 1

Bone Metastases Dosing

• 120 mg subcutaneously every 4 weeks for bone metastases from solid tumors 2, 3
• Initiate at diagnosis of bone metastases regardless of symptoms in breast cancer and castration-resistant prostate cancer 2, 3
• For other solid tumors (lung, renal), use in patients with life expectancy >3 months and clinically significant bone metastases 2, 3
• Do not extend dosing intervals beyond 4 weeks for bone metastases—this cannot be recommended based on current evidence 2

Multiple Myeloma

• Denosumab is the preferred agent in multiple myeloma patients with renal impairment (creatinine clearance <60 mL/min) 2
• Initiate at diagnosis of multiple myeloma 2

Mandatory Pre-Treatment Requirements

Before First Dose

• Perform pregnancy testing in all women of reproductive potential—denosumab can cause fetal harm 1
• Complete dental evaluation and invasive dental procedures before initiating therapy to minimize osteonecrosis of the jaw risk 2, 3, 1
• Correct pre-existing hypocalcemia before starting treatment 1
• In patients with advanced chronic kidney disease (eGFR <30 mL/min/1.73 m²), evaluate for chronic kidney disease mineral and bone disorder with intact PTH, serum calcium, 25(OH) vitamin D, and 1,25(OH)₂ vitamin D 1

Calcium and Vitamin D Supplementation

• All patients must receive calcium 1000-1500 mg daily and vitamin D 400-800 IU daily throughout treatment 2, 3, 1
• Correct vitamin D deficiency before initiating denosumab 2, 3
• This supplementation is particularly critical in patients with advanced chronic kidney disease to prevent severe hypocalcemia 1

Treatment Duration

Osteoporosis

• Continue denosumab throughout the duration of aromatase inhibitor or androgen deprivation therapy, typically up to 2 years, with extension based on clinical judgment 4, 3
• For postmenopausal osteoporosis, treatment duration should be individualized based on fracture risk reassessment 5

Bone Metastases

• Continue monthly denosumab without planned interruption as long as bone disease requires treatment 2, 3
• Do not discontinue after an arbitrary duration except possibly for oligometastatic bone disease in remission 2
• The pharmacokinetics of denosumab argue against intermittent treatment for bone metastases 4

Critical Safety Warning: Discontinuation Protocol

If denosumab must be discontinued for more than 6 months, immediately initiate bisphosphonate therapy to prevent rebound bone loss and multiple vertebral fractures. 2, 6

Transition Strategy

• Administer zoledronic acid 4-5 mg as a single intravenous infusion within 6 months of the last denosumab dose 2, 6
• This prevents the rebound increase in bone resorption that occurs after stopping denosumab 2
• The risk of multiple vertebral fractures following denosumab discontinuation applies to both cancer patients with and without bone metastases 2
• Alternative oral bisphosphonates (risedronate 35 mg weekly) may be used if IV therapy is not feasible 6

Special Populations

Renal Impairment

• No dose adjustment required for any degree of renal impairment 1
• Denosumab is preferred over bisphosphonates in patients with impaired renal function 7, 5
• Patients with advanced chronic kidney disease (eGFR <30 mL/min/1.73 m²) are at markedly increased risk of severe hypocalcemia, especially with underlying CKD-MBD 1
• Monitor calcium and mineral levels (phosphorus, magnesium) closely in these patients 1

Pregnancy and Reproductive Potential

• Contraindicated in pregnancy—can cause fetal harm 1
• Pregnancy testing mandatory before each dose in women of reproductive potential 1
• Adequate contraception required during treatment 4

Key Safety Monitoring

Hypocalcemia

• Monitor serum calcium, especially in patients with advanced chronic kidney disease 1
• Severe hypocalcemia resulting in hospitalization and fatal cases have been reported postmarketing 1
• Ensure adequate calcium and vitamin D supplementation before and during treatment 2, 1

Osteonecrosis of the Jaw

• Complete dental work before initiating therapy 2, 3, 1
• Maintain good oral hygiene during treatment 2

Other Adverse Events

• Monitor for atypical femoral fractures, serious infections, and skin reactions 1, 5
• Increased risk of eczema and cellulitis reported in clinical trials 7

Comparative Efficacy

• Denosumab demonstrated 18% greater delay in time to first skeletal-related event compared to zoledronic acid for bone metastases 4
• For osteoporosis, denosumab reduces vertebral fractures by 70% and hip fractures by 40% 8
• Anti-fracture efficacy equivalent to zoledronic acid but with no residual effect beyond 6 months 8