bisphosphonates

the bone hardeners

Pyrophosphate analogues that bind to hydroxyapatite and inhibit osteoclast activity.

agents & indications

Agent	Route	Indication	Notes
Pamidronate	IV	Hypercalcaemia of Malignancy, Myeloma bone disease.	Older, longer infusion time.
Zoledronic Acid	IV	Hypercalcaemia (Potent), Myeloma, Metastatic bone dz, Osteoporosis.	Most potent. Yearly dosing for osteoporosis.
Alendronate	PO	Osteoporosis.	Strict upright positioning (oesophagitis).

adverse effects

• Nephrotoxicity: Can cause ATN / collapsing FSGS.
  • Action: Dose reduce or contraindicated if eGFR $<30$. Hydrate well.
• Osteonecrosis of the Jaw (ONJ):
  • Risk: High dose/IV therapy, dental extractions.
  • Advice: “Dental clearance” before starting high-dose therapy.
• Acute Phase Reaction: Flu-like symptoms (fever, myalgia) 24-48h after first IV dose. Treat with Acetaminophen.
• Hypocalcaemia: Vitamin D levels must be replete before administration.

contraindications

• Severe Renal Failure (eGFR < 30) - relative (risk vs benefit in severe hypercalcemia).
• Hypocalcaemia.