in patients with hypocalcaemia, and for ten days following Aclasta in patients with Paget's disease of the bone. Monitoring for other mineral metabolism disorders and the avoidance of invasive dental procedures for those who develop osteonecrosis of the jaw is recommended. Zoledronate is rapidly processed via the kidneys; consequently its administration is not recommended for patients with reduced renal function or kidney disease. Some cases of acute kidney injury either requiring dialysis or having a fatal outcome following Reclast use have been reported to the U.S. Food and Drug Administration (FDA). This assessment was confirmed by the European Medicines Agency (EMA), whose Committee for Medicinal Products for Human Use (CHMP) specified new contraindications for the medication on 15 December 2011, which include hypocalcaemia and severe renal impairment with a creatinine clearance of less than 35 ml/min. Bone Osteonecrosis of the jaw 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 zoledronic acid who have had dental extractions. Atypical fractures After approving the drug on 8 July 2009, the European Medicines Agency conducted a class review of all bisphosphonates, including zoledronic acid, after several cases of atypical fractures were reported. In 2008, the EMA's Pharmacovigilance Working Party (PhVWP) noted that alendronic acid was associated with an increased risk of atypical fracture of the femur that developed with low or no trauma. In April 2010, the PhVWP noted that further data from both the published literature and post-marketing reports were now available which suggested that atypical stress fractures of the femur may be a class effect. The European Medicines Agency then reviewed all case reports of stress fractures in patients treated with bisphosphonates, relevant data from the published literature, and data provided by the companies which market bisphosphonates. The Agency recommended that doctors who prescribe bisphosphonate-containing medicines should be aware that atypical fractures may occur rarely in the femur, especially after long-term use, and that doctors who are prescribing these medicines for the prevention or treatment of osteoporosis should regularly review the need for continued treatment, especially after five or more years of use. Pharmacology As a nitrogenous bisphosphonate, Zoledronic acid is a potent inhibitor of bone resorption, allowing the bone-forming cells time to rebuild normal bone and allowing bone remodeling. Research Zoledronic acid has been found to have