Zoledronate.

Zoledronate is the most potent and most long-acting bisphosphonate in clinical use, and is administered as an intravenous infusion. Its major uses are in osteoporosis, Paget's disease, and in myeloma and cancers to reduce adverse skeletal related events (SREs). In benign disease, it is a first- or second-line treatment for osteoporosis, achieving anti-fracture efficacy comparable to that of the RANKL blocker, denosumab, over 3 years, and it reduces fracture risk in osteopenic older women. It is the preferred treatment for Paget's disease, achieving higher rates of remissions which are much more prolonged than with any other agent. Some trials have suggested that it reduces mortality, cardiovascular disease and cancer, but these findings are not consistent across all studies. It is nephrotoxic, so should not be given to those with significant renal impairment, and, like other potent anti-resorptive agents, can cause hypocalcemia in patients with severe vitamin D deficiency, which should be corrected before administration. Its most common adverse effect is the acute phase response, seen in 30-40% of patients after their first dose, and much less commonly subsequently. Clinical trials in osteoporosis have not demonstrated increases in osteonecrosis of the jaw or in atypical femoral fractures. Observational databases are currently inadequate to determine whether these problems are increased in zoledronate users. Now available as a generic, zoledronate is a cost-effective agent for fracture prevention and for management of Paget's disease, but wider provision of infusion facilities is important to increase patient access. There is a need to further explore its potential for reducing cancer, cardiovascular disease and mortality, since these effects could be substantially more important than its skeletal actions.

Bone. 2020 Apr 27 [Epub ahead of print]

Ian R Reid, Jonathan R Green, Kenneth W Lyles, David M Reid, Ulrich Trechsel, David J Hosking, Dennis M Black, Steven R Cummings, R Graham G Russell, Erik F Eriksen

Department of Medicine, University of Auckland, Auckland, New Zealand. Electronic address: ., Novartis AG, Basel, Switzerland., Duke University and VA Medical Centers, Durham, NC, USA., School of Medicine, Dentistry and Nutrition, University of Aberdeen, UK., Nottingham City Hospital, Nottingham, UK., Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA., San Francisco Coordinating Center, Sutter Health Research, San Francisco, CA, USA; Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, CA, USA., Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK; Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK., Department of Clinical Medicine, University of Oslo, Oslo, Norway.