Generic Name

Prolia

Mechanism

• Denosumab binds RANKL with high affinity, preventing interaction with its receptor RANK on osteoclast precursors.
• This blockade inhibits osteoclast formation, activity, and survival, thereby reducing bone resorption.
• The effect is reversible: after stopping treatment, RANKL‑mediated osteoclastogenesis resumes, which may lead to rebound bone loss if therapy is abruptly discontinued.

Pharmacokinetics

Indications

• Postmenopausal osteoporosis (screen‐indicated women ≥70 y or those at high fracture risk).
• Glucocorticoid‑induced osteoporosis (≥ 5‑mg/day prednisone equivalent for ≥ 6 mo).
• Androgen deprivation therapy‑associated osteoporosis in men with prostate cancer.
• Bone metastatic disease from solid tumors (HR ≥ 10 mg/kg SC q6 mo).
• Paget’s disease requiring anti‑resorptive therapy.

Contraindications

• Hypersensitivity to denosumab or any excipient.
• Severe hypocalcemia—must be corrected before initiation.
• Infection risk: actively infected tissues, untreated dental infections.
• Pregnancy/Lactation: category X; no evidence of reproductive risk but theoretical concerns exist.
• History of osteonecrosis of the jaw (ONJ) or atypical femur fractures; monitor closely.

Dosing

• Osteoporosis: 60 mg SC every 6 months (`Prolia`).
• *Schedule*: 60 mg on Day 0, Day 180.
• Bone metastasis: 120 mg SC every 6 months.
• Administration tips:
• Use a pre‑filled syringe or autoinjector; inject into thigh or abdomen.
• Avoid accidental ingestion of calcium‑rich foods after injection without monitoring.

Adverse Effects

• Common
• Upper respiratory infections
• Injection‑site reactions (pain, redness, itching)
• Hypersensitivity rash
• Serious
• Severe hypocalcemia (tetany, seizures)
• Osteonecrosis of the jaw (ONJ)
• Atypical femoral fractures
• Serious infections (osteomyelitis, cellulitis)
• Severe allergic reactions (anaphylaxis)

Monitoring

• Baseline: serum calcium, phosphate, creatinine, 25‑hydroxyvitamin D.
• After each dose:
• Check serum calcium ≥ 2 days post‑injection.
• Monitor renal function every 6 months.
• Dental & Bone Health:
• Dental exam within 6 months prior to initiation.
• DXA scans every 12–24 months (or sooner if indicated).
• Additional: monitor for signs of infection, ONJ, and atypical femur fractures.

Clinical Pearls

• Calcium & Vitamin D Support: Provide at least 1,000 mg elemental calcium and 800 IU vitamin D daily to mitigate hypocalcemia risk.
• Bridge Therapy for Rebound: If discontinuing Prolia, consider a short course of bisphosphonate (e.g., zoledronic acid) to blunt rebound bone loss.
• Dental Precautions: Patients should avoid invasive dental procedures > 6 mo after last dose; maintain good oral hygiene to reduce ONJ risk.
• Avoid Hydroxychloroquine: Some evidence suggests a drug‑drug interaction leading to elevated ONJ risk when combined with denosumab.
• Pregnancy Monitoring: If inadvertent exposure occurs, counsel patient and consider referral to a fertility specialist.

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• Key Takeaway: Prolia’s high‑affinity RANKL inhibition offers potent anti‑resorptive effects, but require diligent calcium monitoring, infection screening, and vigilance for ONJ or atypical fractures. Its dosing schedule (every six months) enhances patient adherence, making it a cornerstone therapy in osteoporosis and bone‑metastatic disease.