Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial

Ann Rheum Dis. 2012 Aug;71(8):1322-8. doi: 10.1136/annrheumdis-2011-200970. Epub 2012 Feb 21.

Abstract

Objectives: 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.

Clinical trial registration number: ACTRN 12609000399291.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / drug therapy
  • Acute-Phase Reaction / etiology
  • Acute-Phase Reaction / pathology
  • Aged
  • Arthralgia / drug therapy*
  • Arthralgia / pathology
  • Arthralgia / physiopathology
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Marrow Diseases / complications
  • Bone Marrow Diseases / drug therapy*
  • Bone Marrow Diseases / pathology
  • Diphosphonates / administration & dosage
  • Diphosphonates / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / therapeutic use*
  • Infusions, Intravenous
  • Knee Joint / drug effects
  • Knee Joint / pathology
  • Knee Joint / physiopathology
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / complications
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / pathology
  • Outcome Assessment, Health Care
  • Pain Measurement
  • Treatment Outcome
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid