title: Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis.
abstract: In a 5-year study involving 119 postmenopausal women, zoledronic acid 4 mg given once-yearly for 2, 3 or 5 years was well tolerated with no evidence of excessive bone turnover reduction or any safety signals. BMD increased significantly. Bone turnover markers decreased from baseline and were maintained within premenopausal reference ranges.
  
  
  BACKGROUND
  After completion of the core study, two consecutive, 2-year, open-label extensions investigated the efficacy and safety of zoledronic acid 4 mg over 5 years in postmenopausal osteoporosis.
  
  
  METHODS
  In the core study, patients received 1 to 4 mg zoledronic acid or placebo. In the first extension, most patients received 4 mg per year and then patients entered the second extension and received 4 mg per year or calcium only. Patients were divided into three subgroups according to years of active treatment received (2, 3 or 5 years). Changes in BMD and bone turnover markers (bone ALP and CTX-I) were assessed.
  
  
  RESULTS
  All subgroups showed substantial increases in BMD and decreases in bone markers. By the end of the core study, 37.5% of patients revealed a suboptimal reduction (< 30%) of bone ALP levels. After subsequent study drug administration during the extensions, there was no evidence of progressive reduction of bone turnover markers. Furthermore, increased marker levels after treatment discontinuation demonstrates preservation of bone remodelling capacity.
  
  
  CONCLUSIONS
  This study showed that zoledronic acid 4 mg once-yearly was well tolerated and effective in reducing biomarkers over 5 years. Detailed analysis of bone marker changes, however, suggests that this drug regimen causes insufficient reduction of remodelling activity in one third of patients.
authors.affiliation: Saint-Luc University Hospital, Université catholique de Louvain, Bruxelles, Belgium. devogelaer@ruma.ucl.ac.be
authors.forename: J P
authors.initials: JP
authors.lastname: Devogelaer
authors.forename: J P
authors.initials: JP
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Burckhardt
authors.forename: P J
authors.initials: PJ
authors.lastname: Meunier
authors.forename: S
authors.initials: S
authors.lastname: Goemaere
authors.forename: K
authors.initials: K
authors.lastname: Lippuner
authors.forename: J J
authors.initials: JJ
authors.lastname: Body
authors.forename: G
authors.initials: G
authors.lastname: Samsioe
authors.forename: D
authors.initials: D
authors.lastname: Felsenberg
authors.forename: T
authors.initials: T
authors.lastname: Fashola
authors.forename: L
authors.initials: L
authors.lastname: Sanna
authors.forename: C E
authors.initials: CE
authors.lastname: Ortmann
authors.forename: U
authors.initials: U
authors.lastname: Trechsel
authors.forename: J
authors.initials: J
authors.lastname: Krasnow
authors.forename: E F
authors.initials: EF
authors.lastname: Eriksen
authors.forename: P
authors.initials: P
authors.lastname: Garnero
mesh_terms: D000328:Adult; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid