What is the default dosage of Prolia (denosumab) Solution For Injection for patients with osteoporosis, particularly postmenopausal women and men with a history of osteoporotic fractures or impaired renal function?

Prolia (Denosumab) Dosage for Osteoporosis

The standard dose of Prolia for osteoporosis is 60 mg administered as a single subcutaneous injection once every 6 months. 1

FDA-Approved Dosing Regimen

• Administer 60 mg subcutaneously every 6 months in the upper arm, upper thigh, or abdomen by a healthcare professional 1
• This dosing schedule applies to all osteoporosis indications: postmenopausal women, men with osteoporosis, glucocorticoid-induced osteoporosis, and cancer treatment-induced bone loss 2, 1
• If a dose is missed, administer the injection as soon as possible, then schedule subsequent injections every 6 months from the date of that last injection 1

Mandatory Supplementation Requirements

• 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 2

Critical Pre-Treatment Requirements

• Rule out pregnancy in all females of reproductive potential before each administration, as denosumab can cause fetal harm 1
• In patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m²), evaluate 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 before initiating treatment 1
• Perform oral examination before starting therapy to identify existing dental disease and minimize osteonecrosis of the jaw risk 3, 2

Efficacy at This Dose

• The 60 mg every 6 months regimen reduces vertebral fractures by 68%, hip fractures by 40%, and nonvertebral fractures by 20% in postmenopausal women with osteoporosis 3, 2, 4
• Long-term extension studies demonstrate sustained efficacy for up to 10 years with continued treatment at this dose 3, 2

Critical Dosing Distinction

• Never use the 120 mg every 4 weeks regimen for osteoporosis treatment - this higher dose is reserved exclusively for bone metastases from solid tumors and carries a significantly increased risk of osteonecrosis of the jaw (5% versus <1% with the 60 mg dose) 2
• The 60 mg every 6 months dose has an acceptable toxicity profile with no increase in osteonecrosis of the jaw compared to placebo 2

Timing Considerations and Fracture Risk

• Delaying subsequent doses by more than 16 weeks after the recommended date increases the risk of vertebral fractures (HR 3.91,95% CI 1.62-9.45) compared to on-time dosing 5
• Maintain strict adherence to the 6-month dosing schedule to prevent rapid reversal of therapeutic effects 4, 5

Special Populations

• Denosumab is particularly appropriate for patients with renal impairment (creatinine clearance <60 mL/min) as it is not cleared through the kidneys, but requires heightened monitoring for hypocalcemia in advanced kidney disease 3, 1
• Treatment in patients with advanced chronic kidney disease should be supervised by a healthcare provider with expertise in CKD-MBD management 1

Critical Safety Warning

• Never discontinue denosumab without immediately transitioning to another antiresorptive agent (preferably high-dose bisphosphonate like zoledronic acid 5 mg) within 6 months of the last dose to prevent rebound vertebral fractures 3, 4