title: Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management.
abstract: Bisphosphonates (BPs) are widely used in the treatment of postmenopausal osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively). The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis), and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.
authors.affiliation: Clinic of Internal Medicine D, Department of Medicine, University of Verona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Dalle Carbonare
authors.forename: Mirko
authors.initials: M
authors.lastname: Zanatta
authors.forename: Adriano
authors.initials: A
authors.lastname: Gasparetto
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Valenti