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

Denosumab Dosage Recommendations

For osteoporosis, administer denosumab (Prolia) 60 mg subcutaneously every 6 months in the upper arm, upper thigh, or abdomen, with mandatory daily supplementation of 1000 mg calcium and at least 400 IU vitamin D. 1

Osteoporosis Dosing Protocol

Standard Dosing:

• 60 mg subcutaneous injection every 6 months is the FDA-approved dose for postmenopausal osteoporosis, male osteoporosis, glucocorticoid-induced osteoporosis, and cancer treatment-induced bone loss 1, 2
• Administer via subcutaneous injection in the upper arm, upper thigh, or abdomen 1
• If a dose is missed, administer as soon as possible and then schedule subsequent injections every 6 months from that date 1

Required 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 receiving bone-affecting treatments 3

Bone Metastases Dosing (Xgeva)

Higher-Dose Regimen:

• 120 mg subcutaneously every 4 weeks for prevention of skeletal-related events in patients with bone metastases from solid tumors 4, 5
• This higher dose and frequency is associated with significantly increased risk of osteonecrosis of the jaw (5% vs <1% with placebo) 4

Critical Distinction: The 120 mg every 4 weeks regimen used in the D-CARE trial showed no improvement in bone metastasis-free survival and had unacceptably high ONJ risk, leading guidelines to recommend against this approach for adjuvant breast cancer treatment 4

Pre-Treatment Requirements

Mandatory Assessments:

• Rule out pregnancy in all females of reproductive potential before each dose 1
• Correct pre-existing hypocalcemia before initiating therapy 1
• Perform oral examination to assess for dental disease and minimize ONJ risk 2, 3

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

• Evaluate for chronic kidney disease mineral and bone disorder (CKD-MBD) with intact PTH, serum calcium, 25(OH) vitamin D, and 1,25(OH)2 vitamin D 1
• Consider assessing bone turnover markers or bone biopsy to evaluate underlying bone disease 1

Efficacy Data Supporting This Dosing

• The 60 mg every 6 months regimen reduces vertebral fractures by 68%, hip fractures by 40%, and non-vertebral fractures by 20% in postmenopausal women 2, 3
• Bone mineral density increases of 6.5-11% occur with 24-48 months of treatment at this dose 6
• Long-term extension studies demonstrate sustained efficacy for up to 10 years with continued treatment 2, 3

Administration Technique

Preparation:

• Remove from refrigerator 15-30 minutes before injection to reach room temperature (up to 25°C/77°F) 1
• Do not warm by any other method 1
• Inspect for particulate matter; solution should be clear, colorless to pale yellow 1

Safety Guard Activation:

• Do NOT activate the green safety guard before injection 1
• After injection, immediately slide the green safety guard over the needle until it locks with a "click" 1
• Dispose immediately in sharps container; never recap the needle 1

Critical Safety Considerations

Discontinuation Risk:

• Stopping denosumab causes rapidly rising bone turnover markers, decreasing bone density, and increased risk of multiple vertebral fractures 7
• Patients must be transitioned to another antiresorptive agent (such as high-dose zoledronic acid 5 mg) within 6 months of the last denosumab dose to prevent rebound fractures 2, 7

Rare but Serious Adverse Effects:

• Osteonecrosis of the jaw (rare at osteoporosis doses; avoid invasive dental procedures during treatment) 2, 3
• Atypical femur fractures 7
• Hypocalcemia (particularly in patients with renal impairment) 2, 1

Common Adverse Effects:

• Arthralgia, nasopharyngitis, back pain, headache, extremity pain, upper respiratory infection 3, 6
• Overall serious adverse event rate similar to placebo (23.8% vs 23.9%) 3