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 a direct antitumor effect and to synergistically augment the effects of other antitumor agents in osteosarcoma cells.Zoledronic acid has shown significant benefits versus placebo over three years, with a reduced number of vertebral fractures and improved markers of bone density. An annual dose of zoledronic acid may also prevent recurring fractures in patients with a previous hip fracture.Zoledronic acid also attenuates accumulation of DNA damage in mesenchymal stem cells and protects their function. With hormone therapy for breast cancer
An increase in disease-free survival (DFS) was found in the ABCSG-12 trial, in which 1,803 premenopausal women with endocrine-responsive early breast cancer received anastrozole with zoledronic acid.
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 EMAs 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.