Retained Skeletal Effects of Zoledronic Acid Following Discontinuation of Treatment: A Review of the Literature.

Abstract

To evaluate the effects on bone mineral density (BMD), bone turnover markers (BTMs), and fracture incidence following zoledronic acid (ZOL) discontinuation. A search of PubMed (1966-May 2016) and International Pharmaceutical Abstracts (1970-May 2016) was conducted using the MeSH terms zoledronic acid, osteoporosis, and withholding treatment. Free text searches included drug holiday and drug discontinuation. An initial review yielded 87 articles. Six articles, which addressed the skeletal effects of ZOL after discontinuation of treatment, were included in the final review. ZOL is a widely prescribed bisphosphonate agent. Studies have shown that discontinuation of ZOL may have lasting skeletal benefits. However, there is inconsistent evidence regarding the duration of the residual skeletal effects of ZOL after treatment discontinuation, or the continued length of therapy required for the prolonged protective benefits on BMD and BTMs. Sample sizes have been small, and studies were not adequately powered to evaluate fracture incidence. A single ZOL infusion has been shown to decrease BTMs and improve BMD for at least 12 months after infusion. Patients may experience continued benefit beyond this period, but there is concern that this long-term effect may lead to severe bone-turnover suppression, increased bone fragility, and increased risk of fractures. Additional extension studies should be conducted to determine the long-term effects of discontinuing ZOL therapy on bone health as well as the length of preserved bone strength after last administration.