Zoledronate

Zoledronate (INN: zoledronic acid, marketed by Novartis under the trade names Zometa and Reclast) is a bisphosphonate. Zometa is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia of malignancy and can be helpful for treating pain from bone metastases.

An annual dose of zoledrinic acid may also prevent recurring fractures in patients with a previous hip fracture. ^[1]

Reclast is a single 5 mg infusion for the treatment of Paget's disease of bone. In 2007, the FDA also approved Reclast for the treatment of postmenopausal osteoporosis.

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Administration

The standard dose for zoledronate is 4 mg to be infused intravenously over 15 min every 3-4 weeks in cancer patients. For Reclast a single dose of 5 mg is used for the treatment of Paget's disease.

Zoledronate has been approved as a once-yearly 5 mg infusion for treatment of osteoporosis and shown significant benefits versus placebo over three years, with a reduced number of vertebral fractures and improved markers of bone density.^{[2] [3]}

Side effects

Side effects can include fatigue, anemia, muscle aches, fever, and/or swelling in the feet or legs. Flu-like symptoms are commonly experienced after the first zoledronate infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human γδ T cells.

Zoledronate is rapidly processed via the kidneys; consequently its administration is not recommended for patients with reduced renal function or kidney disease.

A rare complication that has been recently observed in cancer patients being treated with bisphosphonates is osteonecrosis of the jaw. This has mainly been seen in patients with multiple myeloma treated with zoledronate who have had dental extractions.^[4]

Contraindications

• Poor renal function (e.g. creatinine>3 mg/dL)
• Pregnancy
• Paralysis

References

1. ^ Lyles K, et al. (2007). "Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture". N. Engl. J. Med.. PMID 17878149.
2. ^ Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ (2002). "Intravenous zoledronic acid in postmenopausal women with low bone mineral density". N. Engl. J. Med. 346 (9): 653-61. PMID 11870242.
3. ^ Black et al.. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis. NEJM 2007;356;18;1809-1822. Abstract
4. ^ Durie BG, Katz M, Crowley J (2005). "Osteonecrosis of the jaw and bisphosphonates". N. Engl. J. Med. 353 (1): 99-102; discussion 99-102. PMID 16000365.