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

Prolia (Denosumab) for Osteoporosis Treatment: Recommended Use and Dosage

Prolia (denosumab) is recommended at a dose of 60 mg administered subcutaneously once every 6 months for the treatment of osteoporosis in patients at high risk for fracture, with mandatory calcium (1000 mg) and vitamin D (at least 400 IU) supplementation daily. 1

Indications for Prolia

Prolia is FDA-approved for:

1. Treatment of postmenopausal women with osteoporosis at high risk for fracture
2. Treatment to increase bone mass in men with osteoporosis
3. Treatment of glucocorticoid-induced osteoporosis
4. Treatment of bone loss in men receiving androgen deprivation therapy for prostate cancer
5. Treatment of bone loss in women receiving aromatase inhibitor therapy for breast cancer 1

High fracture risk is defined as:

• History of osteoporotic fracture
• Multiple risk factors for fracture
• Failure or intolerance to other available osteoporosis therapy 1

Place in Therapy

Prolia is generally recommended as a second-line therapy after oral bisphosphonates:

• Oral bisphosphonates are preferred first-line therapy for safety, cost, and established efficacy 2, 3
• Prolia should be considered when:
  • Oral bisphosphonates are contraindicated
  • Patient is intolerant to oral bisphosphonates
  • Patient has failed other osteoporosis treatments 3

Administration and Dosing

• Dose: 60 mg subcutaneous injection
• Frequency: Every 6 months
• Administration sites: Upper arm, upper thigh, or abdomen
• Must be administered by a healthcare professional 1
• All patients must receive daily calcium (1000 mg) and vitamin D (at least 400 IU) supplementation 1

Pre-Treatment Considerations

1. Pregnancy testing: Must be ruled out prior to administration in females of reproductive potential 1

2. Kidney function assessment:

   • For patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m²):
     • Evaluate for chronic kidney disease-mineral bone disorder (CKD-MBD)
     • Check iPTH, serum calcium, and vitamin D levels
     • Treatment should be supervised by a provider with expertise in CKD-MBD 1

Efficacy

Denosumab has demonstrated significant efficacy in reducing fracture risk:

• 68% reduction in new vertebral fractures
• 40% reduction in hip fractures
• 20% reduction in nonvertebral fractures 4

Denosumab increases bone mineral density (BMD) progressively over time with continued use, with sustained fracture risk reduction 5

Safety Considerations and Monitoring

Common Adverse Effects

• Hypocalcemia (particularly in patients with advanced kidney disease)
• Back pain
• Pain in extremities
• Musculoskeletal pain 1, 6

Serious Adverse Effects

1. Severe hypocalcemia: Risk is higher in patients with advanced kidney disease 1

2. Discontinuation effects:

   • Rebound increase in bone turnover after stopping denosumab
   • Risk of multiple vertebral fractures
   • Transition to bisphosphonate therapy recommended when stopping denosumab 2, 6, 5

3. Rare but serious complications:

   • Osteonecrosis of the jaw (ONJ)
   • Atypical femoral fractures (AFFs)
   • Maintain good oral hygiene and ensure regular dental reviews 2, 6

Follow-up and Monitoring

• Bone mineral density (BMD) testing every 2 years 3
• If a dose is missed, administer as soon as possible and reschedule subsequent injections every 6 months from the date of the last injection 1

Advantages of Prolia

• Convenient dosing schedule (twice yearly) may improve adherence compared to other treatments 7
• Subcutaneous administration may be preferred by some patients 7
• Effective option for patients who cannot tolerate oral bisphosphonates 6
• Progressive BMD increases with long-term use 5

Prolia represents an important treatment option for osteoporosis, particularly for patients who cannot use or have failed other therapies, with proven efficacy in reducing fracture risk across multiple skeletal sites.