Zoledronic acid

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A nitrogen containing bisphosphonate administered parentally that in osteoporosis related presentations has demonstrated better reductions in fracture rates than oral therapy and in patients with fractured neck of femur a 3.7% reduction in all cause mortality accrued at 3 years without reducing significantly further fractures at the hip.[1]

Clinical Use




  • 4mg every 3-4 weeks (reduction of bone damage in malignancy)
  • 4mg stat(hypercalcaemia of malignancy)
  • 5mg iv over 15 minutes annually (unlicensed as of 2007) produces the most convincing reductions in fracture rates (but not of the hip after other hip fracture !) so far demonstrated for a bisphosphonate in postmenopausal osteoporosis[2][3][4] Perhaps the reason is greater compliance.

Clinical Issues

  • Long term studies in osteoporosis do not exist. In clinical trials in osteoporosis patients who were vitamin D deficient were given loading doses of Vitamin D.
  • The preliminary evidence of a reduction in mortality associated with administration in malignancies associated with bone metastatic disease has not been confirmed.


Cautions and Interactions

  • Renal failure

Side effects

  • Hypocalcaemia
  • Atrial fibrillation
  • Nausea
  • Diarrhoea
  • Abdomenal pain and distension
  • Flatulence
  • Dyspepsia
  • In long term use (> 7 years) atypical femoral stem fractures have been associated with alendronate and the potential for decreased bone healing and increasing differential fracture risk is a concern for all bisphosphonates due to their mechanism of action[5]
  • Atrial fibrillation (subject to on going analysis by regulatory agencies).
  • Uveitis (adjusted relative risk = 1.5, 95% CI 1.3 to 1.7) and scleritis (adjusted relative risk = 1.5, 95% CI 1.3 to 1.7)
  • Possibly oesophageal malignancy[6]

Oral bisphosphonates

  • Oesophageal ulceration
    • Patient needs assessment if
      • Dyspepsia
      • Heart burn
      • Pain on swallowing
      • Retrosternal pain

Nitrogen-containing bisphosphonates

Nitrogen containing iv bisphosphonates

  • Acute phase reaction with
    • Fever
    • Myalgia
    • Influenzae like symptoms

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