title: Intravenous zoledronic acid in postmenopausal women with low bone mineral density.
abstract: BACKGROUND
  Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored.
  
  
  METHODS
  We studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point.
  
  
  RESULTS
  There were similar increases in bone mineral density in all the zoledronic acid groups to values for the spine that were 4.3 to 5.1 percent higher than those in the placebo group (P<0.001) and values for the femoral neck that were 3.1 to 3.5 percent higher than those in the placebo group (P<0.001). Biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups. Myalgia and pyrexia occurred more commonly in the zoledronic acid groups, but treatment-related dropout rates were similar to that in the placebo group.
  
  
  CONCLUSIONS
  Zoledronic acid infusions given at intervals of up to one year produce effects on bone turnover and bone density as great as those achieved with daily oral dosing with bisphosphonates with proven efficacy against fractures, suggesting that an annual infusion of zoledronic acid might be an effective treatment for postmenopausal osteoporosis.
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand. i.reid@auckland.ac.nz
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Brown
authors.forename: Peter
authors.initials: P
authors.lastname: Burckhardt
authors.forename: Zebulun
authors.initials: Z
authors.lastname: Horowitz
authors.forename: Peter
authors.initials: P
authors.lastname: Richardson
authors.forename: Ulrich
authors.initials: U
authors.lastname: Trechsel
authors.forename: Albert
authors.initials: A
authors.lastname: Widmer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Devogelaer
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kaufman
authors.forename: Philippe
authors.initials: P
authors.lastname: Jaeger
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Body
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
authors.forename: Johann
authors.initials: J
authors.lastname: Broell
authors.forename: Raffaele
authors.initials: R
authors.lastname: Di Micco
authors.forename: Andrea Riccardo
authors.initials: AR
authors.lastname: Genazzani
authors.forename: Dieter
authors.initials: D
authors.lastname: Felsenberg
authors.forename: Joachim
authors.initials: J
authors.lastname: Happ
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hooper
authors.forename: Jochen
authors.initials: J
authors.lastname: Ittner
authors.forename: Georg
authors.initials: G
authors.lastname: Leb
authors.forename: Hans
authors.initials: H
authors.lastname: Mallmin
authors.forename: Timothy
authors.initials: T
authors.lastname: Murray
authors.forename: Sergio
authors.initials: S
authors.lastname: Ortolani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rubinacci
authors.forename: Maria
authors.initials: M
authors.lastname: Saaf
authors.forename: Goran
authors.initials: G
authors.lastname: Samsioe
authors.forename: Leon
authors.initials: L
authors.lastname: Verbruggen
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Meunier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D003094:Collagen / Q000097:blood / Q000652:urine; D024042:Collagen Type I; D003404:Creatinine / Q000652:urine; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D007262:Infusions, Intravenous; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D010455:Peptides / Q000097:blood / Q000652:urine; D000077211:Zoledronic Acid
chemical_list: D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid; D003094:Collagen; D003404:Creatinine