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.
- 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 Perhaps the reason is greater compliance.
- 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
- Atrial fibrillation
- Abdomenal pain and distension
- 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
- 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
- Oesophageal ulceration
- Patient needs assessment if
- Heart burn
- Pain on swallowing
- Retrosternal pain
- Patient needs assessment if
- Osteonecrosis (of jaw) in dose related association
Nitrogen containing iv bisphosphonates
- Acute phase reaction with
- Influenzae like symptoms
- ↑ Lyles KW, Colón-Emeric CS, Magaziner JS et al. Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture NEJM 2007 10.1056/NEJMoa074941
- ↑ Black DM, Delmas PD, Eastell R et al Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007;356(18):1809-1821
- ↑ McClung M, Recker R, Miller P, Fiske D, Minkoff J, Kriegman A, Zhou W, Adera M, Davis J. Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone. 2007
- ↑ Saag K, Lindsay R, Kriegman A, Beamer E, Zhou W A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density. Bone. 2007;40(5):1238-43
- ↑ Lenart BA, Lorich DG, Lane JM.Atypical femoral fractures and Aldrenonate NEJM 2008;358:1304-1305
- ↑ Green J, Czanner G, Reeves G, Watson J, Wise L, Beral V. Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort. BMJ (Clinical research ed.). 2010; 341:c4444.(Epub)