How to Initiate Prolia (Denosumab)
Administer Prolia 60 mg subcutaneously once every 6 months, ensuring all patients receive calcium 1000 mg daily and at least 400 IU vitamin D daily, with mandatory pregnancy testing in females of reproductive potential and pre-treatment oral examination to minimize osteonecrosis of the jaw risk. 1
Pre-Treatment Assessment and Laboratory Testing
Mandatory Screening Requirements
Rule out pregnancy in all females of reproductive potential before administering Prolia, as denosumab can cause fetal harm 1
Perform oral examination before initiating therapy to assess for dental disease and minimize osteonecrosis of the jaw (ONJ) risk 2
Evaluate renal function in patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m²), including dialysis-dependent patients, by measuring intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25(OH)₂ vitamin D to assess for chronic kidney disease mineral and bone disorder (CKD-MBD) 1
Correct vitamin D deficiency prior to initiation, as deficiency may attenuate efficacy and increase risk of bisphosphonate-related hypocalcemia 3
Patient Selection Criteria
Consider denosumab for patients who have failed or are intolerant to other available osteoporosis therapy, including oral and IV bisphosphonates 2
Denosumab is particularly appropriate for patients with renal impairment (creatinine clearance <60 ml/min) due to its superior renal safety profile, as it is not cleared through the kidneys 2, 4
Select denosumab for patients with cancer-related bone disease (breast cancer, prostate cancer, or multiple myeloma) where it has demonstrated efficacy in reducing fracture risk 2, 4
Administration Protocol
Dosing and Route
Administer 60 mg subcutaneously once every 6 months by a healthcare professional 1
Injection sites include: upper arm, upper thigh, or abdomen 1
Do NOT administer into muscle or blood vessel 1
Timing and Adherence
Maintain precise 6-month intervals to prevent rapid rebound in bone turnover and increased vertebral fracture risk 5
If a dose is missed, administer the injection as soon as the patient is available, then schedule subsequent injections every 6 months from the date of the last injection 1
During exceptional circumstances (e.g., pandemic), extending dosing intervals to no longer than 8 months may be acceptable, though this is not ideal 5
Preparation Instructions
Remove Prolia from refrigerator and bring to room temperature (up to 25°C/77°F) by standing in the original container for 15-30 minutes 1
Do NOT warm Prolia in any other way 1
Inspect visually for particulate matter and discoloration; do not use if solution is discolored, cloudy, or contains many particles 1
Mandatory Supplementation
All patients must receive calcium 1000 mg daily and at least 400 IU vitamin D daily throughout treatment 1, 2
This supplementation is critical to prevent hypocalcemia, particularly in patients with renal impairment 2
Safety Monitoring and Patient Education
Critical Safety Warnings
Never discontinue denosumab without immediately starting bisphosphonate therapy (zoledronic acid 5 mg) within 6 months of the last dose to prevent rebound vertebral fractures 3, 2
Avoid invasive dental procedures during treatment to minimize ONJ risk 2
Monitor for signs of hypocalcemia, especially in patients with renal impairment, as asymptomatic hypocalcemia may occur 2
Expected Adverse Effects
Common adverse effects include arthralgia, nasopharyngitis, headache, back pain, and upper respiratory infections 2
Rare but serious complications include osteonecrosis of the jaw (incidence <1 case per 100,000 person-years), atypical femur fractures, and hypocalcemia 2, 3
Monitoring Schedule
Check calcium and vitamin D levels prior to initial dose 2
Follow-up DEXA scan in 2 years to assess treatment response 2
Clinical assessment at regular intervals for potential adverse effects 2
The American College of Physicians recommends against routine BMD monitoring during the initial 5-year treatment period, as fracture reduction occurs even without BMD increases 3
Expected Clinical Outcomes
Denosumab reduces vertebral fractures by 68%, hip fractures by 40%, and non-vertebral fractures by 20% in postmenopausal women with osteoporosis 2
BMD increases are rapid and significant, with increases of 4.2% in lumbar spine and 3.1% in femoral neck at 12 months 6
Bone resorption marker (CTX-I) decreases by 54% at 6 months and 72% at 12 months, demonstrating potent antiresorptive activity 6
Common Pitfalls to Avoid
Do NOT allow treatment gaps or delays beyond 6 months, as denosumab's effects are time-limited and reversible, unlike bisphosphonates which are stored in bone 5
Do NOT discontinue denosumab without transition planning, as this creates severe rebound fracture risk 3, 2
Ensure dental work is completed before initiating therapy to reduce ONJ risk 3
Do NOT use denosumab as adjuvant therapy in breast cancer, as the D-CARE trial showed no improvement in cancer outcomes 3