What is the recommended dose of Denosumab (Prolia/Xgeva) for osteoporosis and bone metastases?

Denosumab Dosing Recommendations

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

Osteoporosis Dosing

The FDA-approved and guideline-recommended dose for all osteoporosis indications is 60 mg subcutaneously every 6 months. 1

This single dosing regimen applies to:

• Postmenopausal osteoporosis 2, 1
• Male osteoporosis 2, 1
• Glucocorticoid-induced osteoporosis (in patients on ≥7.5 mg prednisone equivalent daily for ≥6 months) 2, 1
• Cancer treatment-induced bone loss (androgen deprivation therapy for prostate cancer or aromatase inhibitor therapy for breast cancer) 2, 1

Administration Details

• Inject subcutaneously in the upper arm, upper thigh, or abdomen 1
• Must be administered by a healthcare professional 1
• If a dose is missed, administer as soon as possible, then resume every 6 months from that date 1

Mandatory Supplementation

All patients must receive calcium 1000 mg daily and at least 400 IU vitamin D daily 1. Some guidelines recommend higher vitamin D supplementation of 1000-2000 IU daily for patients on bone-affecting treatments 2, 3.

Bone Metastases Dosing

For prevention of skeletal-related events in patients with bone metastases from solid tumors, use denosumab 120 mg subcutaneously every 4 weeks. 2

Critical Safety Distinction

This higher dose (120 mg every 4 weeks) carries a significantly increased risk of osteonecrosis of the jaw (ONJ): 5% versus <1% with placebo 2. The ASCO guideline specifically notes that the D-CARE trial using this higher dose showed unacceptably high ONJ risk (5% vs <1%) and did not improve bone metastasis-free survival 4.

Do not use the 120 mg every 4 weeks regimen for osteoporosis treatment - the 60 mg every 6 months dose has acceptable toxicity with no increase in ONJ 4.

Efficacy Data for Osteoporosis Dose

The 60 mg every 6 months regimen demonstrates:

• 68% reduction in vertebral fractures 2, 5
• 40% reduction in hip fractures 2, 5
• 20% reduction in non-vertebral fractures 2, 5
• Sustained efficacy for up to 10 years with continued treatment 2, 5

Pre-Treatment Requirements

For All Patients

• Correct pre-existing hypocalcemia before initiating therapy 1
• Pregnancy testing required in all females of reproductive potential 1
• Oral examination required to assess for dental disease and minimize ONJ risk 5, 3

For Advanced Chronic Kidney Disease (eGFR <30 mL/min/1.73 m²)

Before initiating denosumab, evaluate:

• Intact parathyroid hormone (iPTH) 1
• Serum calcium 1
• 25(OH) vitamin D 1
• 1,25(OH)₂ vitamin D 1
• Consider bone turnover markers or bone biopsy 1

No dose adjustment needed for renal impairment, but enhanced monitoring for hypocalcemia is essential 6, 7.

Critical Discontinuation Warning

Stopping denosumab causes rapidly rising bone turnover markers, decreasing bone density, and increased risk of multiple vertebral fractures. 2, 8

Patients must be transitioned to another antiresorptive agent (preferably high-dose zoledronic acid 5 mg) within 6 months of the last denosumab dose to prevent rebound bone loss and fractures 2, 5, 8.

Adjuvant Breast Cancer Context

ASCO guidelines do not recommend denosumab to reduce breast cancer recurrence due to conflicting trial results 4:

• ABCSG-18 trial: 60 mg every 6 months showed modest DFS benefit (HR 0.82) with acceptable toxicity 4
• D-CARE trial: 120 mg every 4 weeks showed no benefit and unacceptably high ONJ risk (5%) 4

However, the 60 mg every 6 months dose remains appropriate for treating osteoporosis or bone loss in these patients, not for anticancer effects 4.