Generic Name

Reclast

Mechanism

Reclast (zoledronic acid) is a third‑generation nitrogen‑containing bisphosphonate.
• It binds avidly to hydroxyapatite in bone, becoming incorporated into the bone matrix.
• When osteoclasts resorb bone, zoledronic acid is released and inhibits farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway.
• FPPS inhibition blocks geranylgeranylation of small GTP‑binding proteins (Ras, Rho, Rac) essential for osteoclast cytoskeletal organization, survival, and resorption activity.
• Result: ↓ osteoclast‑mediated bone resorption → ↑ bone mineral density (BMD) and ↓ fracture risk.

Pharmacokinetics

Indications

• Post‑menopausal osteoporosis – prevent vertebral, non‑vertebral, and hip fractures.
• Glucocorticoid‑induced osteoporosis – reduce fracture risk in patients on long‑term steroids.
• Paget’s disease of bone – control excessive bone turnover.
• Multiple myeloma and metastatic bone disease – alleviate bone pain and reduce skeletal‑related events (used off‑label in some regions).

Contraindications

• Severe renal impairment (CrCl  8.5 mg/dL before infusion.
• Pregnancy / lactation – teratogenic potential; contraindicated.
• Osteonecrosis of the jaw (ONJ) – patients with invasive dental procedures or poor oral hygiene are at increased risk.
• Atypical femoral fractures – monitor for prodromal pain.

Dosing

*Infusion protocol:*
1. Verify serum Ca²⁺ > 8.5 mg/dL and normal renal function.
2. Administer 5 mg in 100 mL normal saline over 30 min.
3. Advise oral calcium + vitamin D supplementation.
4. Monitor for infusion reactions (rare).

Adverse Effects

Common (≤ 10 %)
• Flu‑like symptoms: fever, myalgia, arthralgia, headache.
• Transient hypocalcemia.
• GI upset (rare; oral formulations only).

Serious (≤ 1 %)
• Osteonecrosis of the jaw (ONJ).
• Atypical femoral fractures.
• Severe hypocalcemia.
• Renal dysfunction (rare with proper screening).

Monitoring

• Baseline: serum creatinine, eGFR, Ca²⁺, PTH, 25‑OH‑vitamin D.
• During therapy:
• Monitor Ca²⁺ within 24 h post‑infusion; repeat if symptomatic.
• eGFR annually (or more frequently if CrCl < 60 mL/min).
• Bone turnover markers (ALP, CTX) in Paget’s disease or monitoring response.
• Dental evaluation before therapy; avoid invasive dental work during treatment.

Clinical Pearls

• “One‑and‑done” therapy: For most post‑menopausal osteoporosis patients, a single annual infusion provides benefits for up to 5 years; consider switch to oral bisphosphonate if renal function declines.
• Renal safety window: Even with CrCl 35–49 mL/min, a single dose is acceptable; avoid repeat dosing until renal function improves.
• Bone‑sparing strategy: In patients with long‑term steroid use, combine with calcium + vitamin D and consider anti‑resorptive therapy after 12 months of steroids.
• ONJ prevention: Perform pre‑infusion dental exam; discontinue therapy if invasive dental procedures are needed; maintain strict oral hygiene.
• Atypical fracture red flags: Persistent thigh or groin pain in long‑term users warrants imaging and potential drug holiday.
• Infusion technique: Slow infusion (≤ 30 min) reduces flu‑like reactions; use 100 mL saline diluent to avoid hemoconcentration.
• Drug interactions: Avoid concomitant use with calcitonin or denosumab without careful monitoring, as overlapping anti‑resorptive effects may increase ONJ risk.

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• Key takeaways: Reclast’s potent, long‑lasting inhibition of osteoclasts makes it a first‑line choice for high‑risk osteoporosis and Paget’s disease, but vigilance for renal function, calcium status, and ONJ is essential for safe use.