title: Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial.
abstract: OBJECTIVE
  To compare the effect of a single infusion of zoledronic acid (ZA) with placebo on knee pain and bone marrow lesions (BMLs).
  
  
  METHODS
  Adults aged 50-80 years (n=59) with clinical knee osteoarthritis and knee BMLs were randomised to receive either ZA (5 mg/100 ml) or placebo. BMLs were determined using proton density-weighted fat saturation MR images at baseline, 6 and 12 months. Pain and function were measured using a visual analogue scale (VAS) and the knee injury and osteoarthritis outcome score (KOOS) scale.
  
  
  RESULTS
  At baseline, mean VAS score was 54 mm and mean total BML area was 468 mm(2). VAS pain scores were significantly reduced in the ZA group compared with placebo after 6 months (-14.5 mm, 95% CI -28.1 to -0.9) but not after 3 or 12 months. Changes on the KOOS scales were not significant at any time point. Reduction in total BML area was greater in the ZA group compared with placebo after 6 months (-175.7 mm(2), 95% CI -327.2 to -24.3) with a trend after 12 months (-146.5 mm(2), 95% CI -307.5 to +14.5). A greater proportion of those in the ZA group achieved a clinically significant reduction in BML size at 6 months (39% vs 18%, p=0.044). Toxicity was as expected apart from a high rate of acute phase reactions in treatment and placebo arms.
  
  
  CONCLUSIONS
  ZA reduces knee pain and areal BML size and increases the proportion improving over 6 months. Treatment of osteoarthritis may benefit from a lesion specific therapeutic approach.
  
  
  BACKGROUND
  ACTRN 12609000399291.
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia. Laura.Laslett@utas.edu.au
authors.forename: Laura Louise
authors.initials: LL
authors.lastname: Laslett
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Doré
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Quinn
authors.forename: Philippa
authors.initials: P
authors.lastname: Boon
authors.forename: Emma
authors.initials: E
authors.lastname: Ryan
authors.forename: Tania Maree
authors.initials: TM
authors.lastname: Winzenberg
authors.forename: Graeme
authors.initials: G
authors.lastname: Jones
mesh_terms: D000210:Acute-Phase Reaction / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D000368:Aged; D018771:Arthralgia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017063:Outcome Assessment, Health Care; D010147:Pain Measurement; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid