What is the recommended use and dosage of Prolia (denosumab) for osteoporosis treatment?

Prolia (Denosumab) for Osteoporosis Treatment

Prolia (denosumab) 60 mg should be administered subcutaneously every 6 months for the treatment of postmenopausal osteoporosis in women at high risk for fracture, men with osteoporosis, and patients with glucocorticoid-induced osteoporosis. 1

Approved Indications

Prolia is FDA-approved for:

• Postmenopausal women with osteoporosis at high risk for fracture (history of osteoporotic fracture, multiple risk factors, or failed/intolerant to other therapies) 1
• Men with osteoporosis at high risk for fracture 1
• Glucocorticoid-induced osteoporosis in patients receiving ≥7.5 mg prednisone equivalent daily for ≥6 months 1
• Men receiving androgen deprivation therapy for nonmetastatic prostate cancer 1
• Women receiving aromatase inhibitor therapy for breast cancer 1

Dosing and Administration

The standard dose is 60 mg administered subcutaneously once every 6 months by a healthcare professional. 1

• Injection sites include upper arm, upper thigh, or abdomen 1
• If a dose is missed, administer as soon as possible, then resume every 6 months from that date 1
• All patients must receive calcium 1000 mg daily and at least 400 IU vitamin D daily 1

Pre-Treatment Requirements

Mandatory Assessments

• Pregnancy testing in all females of reproductive potential - denosumab can cause fetal harm and is contraindicated in pregnancy 1
• Correct pre-existing hypocalcemia before initiating therapy 1
• Oral/dental examination to assess for dental disease and minimize osteonecrosis of the jaw risk 2, 3

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

Evaluate for chronic kidney disease mineral and bone disorder (CKD-MBD) with: 1

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

Clinical Efficacy

Denosumab demonstrates superior fracture reduction compared to placebo: 4

• 68% reduction in vertebral fractures (2.3% vs 7.2% with placebo) 4
• 40% reduction in hip fractures (0.7% vs 1.2% with placebo) 4
• 20% reduction in nonvertebral fractures (6.5% vs 8.0% with placebo) 4

Position in Treatment Algorithm

The American College of Physicians recommends oral bisphosphonates as first-line therapy for most patients with osteoporosis. 2

When to Use Denosumab

Denosumab is appropriate for: 2

• Patients who have failed or are intolerant to bisphosphonates (oral or IV)
• Patients with contraindications to bisphosphonates
• Patients with impaired renal function (can be used when bisphosphonates are contraindicated)
• High-risk patients requiring potent antiresorptive therapy

Critical Safety Warnings

Rebound Vertebral Fractures After Discontinuation

This is the most serious risk with denosumab. Unlike bisphosphonates, denosumab does not incorporate into bone matrix, leading to rapid bone loss upon discontinuation. 2

• Multiple vertebral fractures can occur after stopping denosumab 2
• Bone turnover markers increase steeply and BMD decreases rapidly after cessation 2
• Patients must transition to bisphosphonate therapy (typically zoledronic acid 5 mg) within 6 months of the last denosumab dose to prevent rebound bone loss 2, 5

Osteonecrosis of the Jaw (ONJ)

• Patients should avoid invasive dental procedures (extractions, implants) during therapy if possible 2
• Maintain good oral hygiene and regular dental review 2
• When tooth extraction is unavoidable, use prophylactic antibiotics and suspend denosumab until healing is complete 2

Atypical Femoral Fractures

• Risk is low (3.2-50 per 100,000 person-years) but increases with long-term use 2
• More common after median 7 years of treatment 2
• Characterized by transverse fracture line, periosteal callus, prodromal pain, and potential bilaterality 2

Hypocalcemia

• Can occur, particularly in patients with renal impairment 1, 6
• Must correct hypocalcemia before starting therapy 1
• Ensure adequate calcium and vitamin D supplementation 1

Monitoring Recommendations

• Clinical assessment for adverse effects at regular intervals 3
• DEXA scan monitoring at 1-2 year intervals (not required before each dose authorization per ESMO guidelines) 3
• The American College of Physicians recommends against routine BMD monitoring during the first 5 years of bisphosphonate therapy, but denosumab's unique pharmacology may warrant different approaches 3

Common Pitfalls to Avoid

• Never discontinue denosumab without a transition plan - this leads to rebound bone loss and multiple vertebral fractures 2
• Do not delay sequential bisphosphonate therapy after stopping denosumab - must initiate within 6 months 2, 5
• Do not overlook calcium and vitamin D supplementation - mandatory for all patients 1
• Do not skip pre-treatment dental evaluation - critical for preventing ONJ 2, 3
• Do not use in pregnant women - can cause fetal harm 1