Prolia (Denosumab) Dosage for Osteoporosis
The FDA-approved dose of Prolia is 60 mg administered as a single subcutaneous injection once every 6 months, with mandatory calcium (at least 1000 mg daily) and vitamin D (at least 400 IU daily) supplementation. 1
Administration Details
- Route and frequency: Administer 60 mg subcutaneously every 6 months in the upper arm, upper thigh, or abdomen by a healthcare professional 1
- Timing flexibility: If a dose is missed, administer as soon as possible, then schedule subsequent injections 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 (though 600-800 IU is commonly recommended) 1, 2
Pre-Treatment Requirements
For All Patients
- Pregnancy testing: Must rule out pregnancy in all females of reproductive potential before each dose, as denosumab can cause fetal harm 1
- Calcium and vitamin D optimization: Ensure adequate supplementation before initiating therapy to prevent hypocalcemia 1
For Patients with Advanced Chronic Kidney Disease (eGFR <30 mL/min)
- Critical warning: These patients, including those on dialysis, are at significantly greater risk of severe, potentially fatal hypocalcemia 1
- Required evaluation: Assess for chronic kidney disease-mineral bone disorder (CKD-MBD) by measuring intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25(OH)2 vitamin D 1
- Specialist supervision: Treatment should be supervised by a provider with expertise in CKD-MBD diagnosis and management 1
Treatment Duration Considerations
- Long-term efficacy: Denosumab demonstrates sustained fracture reduction and continued BMD increases for up to 10 years of continuous treatment 2
- No drug holidays: Unlike bisphosphonates, denosumab does NOT incorporate into bone matrix and cannot be safely discontinued without immediate transition to alternative therapy 2
- Critical discontinuation warning: Stopping denosumab without replacement therapy causes rapid rebound bone turnover with significantly increased risk of multiple vertebral fractures 2, 3
Safety Monitoring
- Dental evaluation: Perform oral examination before initiating therapy to assess for dental disease and minimize osteonecrosis of the jaw (ONJ) risk 2
- Hypocalcemia monitoring: Watch for signs of hypocalcemia, particularly in patients with renal impairment 2
- Rare but serious risks: ONJ and atypical femoral fractures can occur, though absolute risk remains low 2
Clinical Efficacy
- Fracture reduction: Denosumab reduces vertebral fractures by 68%, hip fractures by 40%, and nonvertebral fractures by 20% compared to placebo 2, 4
- BMD improvements: Produces continuous BMD increases at all skeletal sites throughout treatment duration 5, 6
Common Pitfall to Avoid
Never discontinue denosumab without immediately planning transition to high-dose bisphosphonate therapy (such as zoledronic acid 5 mg) within 6 months of the last dose, as this can result in catastrophic multiple vertebral fractures. 2, 3 This represents the most critical safety consideration distinguishing denosumab from bisphosphonates.