What is the role of Prolia (denosumab) in treating osteoporosis?

Prolia (Denosumab) Treatment for Osteoporosis

Denosumab (Prolia) is recommended as a second-line pharmacologic treatment for osteoporosis in patients who have contraindications to or experience adverse effects of bisphosphonates, which remain the first-line therapy. 1

Mechanism of Action and Efficacy

• Denosumab is a human monoclonal antibody that targets RANKL (receptor activator of nuclear factor kappa-B ligand), inhibiting osteoclast formation, function, and survival, thereby reducing bone resorption 2, 3
• Administered as a subcutaneous injection of 60 mg once every 6 months 4
• In postmenopausal women with osteoporosis, denosumab significantly reduces the risk of:
  • Vertebral fractures by 68% compared to placebo 5
  • Hip fractures by 40% 5
  • Nonvertebral fractures by 20% 5
• Increases bone mineral density (BMD) at all skeletal sites, including lumbar spine and total hip 6
• Benefits are generally evident after the first dose and maintained during long-term treatment of up to 8 years 6

Indications

Prolia is FDA-approved for:

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

Place in Therapy

• Bisphosphonates (alendronate, risedronate, zoledronate) remain first-line treatment for osteoporosis due to their favorable balance of benefits, harms, patient preferences, and lower cost 1
• Denosumab is recommended as second-line therapy for patients who:
  • Have contraindications to bisphosphonates 1
  • Experience adverse effects from bisphosphonates 1
  • Have failed bisphosphonate therapy 4
• May be considered as first-line in patients at high risk for fracture who cannot take oral bisphosphonates due to dosing difficulties 7

Safety and Adverse Effects

• Generally well tolerated in clinical trials 2, 5
• Common side effects include:
  • Back pain, pain in arms and legs, muscle pain 4
  • High cholesterol, bladder infection 4
• Important potential adverse effects include:
  • Hypocalcemia (particularly in patients with advanced kidney disease) 4
  • Serious infections 4
  • Skin reactions (dermatitis, rash, eczema) 4
  • Osteonecrosis of the jaw (uncommon) 4
  • Atypical femoral fractures (uncommon) 4

Important Considerations and Warnings

• Rebound bone loss after discontinuation: Denosumab discontinuation is associated with multiple vertebral fractures in some patients 1, 7

  • After stopping denosumab, bisphosphonate therapy should be considered to prevent rebound bone resorption 1
  • Patients should not stop, skip, or delay doses without consulting their physician 4

• Pregnancy: Must be ruled out prior to administration as denosumab can cause fetal harm 4

• Hypocalcemia risk: Particularly high in patients with advanced kidney disease (eGFR < 30 mL/min/1.73m²) 4

  • Prior to initiating in these patients, evaluate for chronic kidney disease-mineral bone disorder (CKD-MBD) 4
  • Treatment should be supervised by a healthcare provider with expertise in CKD-MBD 4

• Dental procedures: Patients should have dental examination before starting therapy and maintain good oral hygiene during treatment 4

Monitoring and Administration

• Calcium and vitamin D supplementation is required during treatment 4
• No evidence supports routine bone mineral density monitoring during treatment 1
• Administered by healthcare professionals as a subcutaneous injection in the upper arm, upper thigh, or abdomen 4
• Treatment is given once every 6 months, which may improve adherence compared to other osteoporosis treatments 3

Long-term Considerations

• Long-term treatment (up to 10 years) maintains anti-fracture efficacy and safety profile 2
• The optimal duration of therapy and management after discontinuation remain areas of ongoing research 7
• For patients discontinuing denosumab, transition to a bisphosphonate is recommended to prevent rebound bone loss 1