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Extended report
Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial
  1. Laura Louise Laslett1,
  2. Dawn A Doré1,
  3. Stephen J Quinn2,
  4. Philippa Boon1,
  5. Emma Ryan1,
  6. Tania Maree Winzenberg1,
  7. Graeme Jones1
  1. 1Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia
  2. 2Clinical Effectiveness Cluster, Flinders University, Adelaide, South Australia, Australia
  1. Correspondence to Laura Louise Laslett, University of Tasmania, Menzies Research Institute Tasmania, Private Bag 23, Hobart, Tasmania, Australia, 7000; Laura.Laslett{at}


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 mm2. 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 mm2, 95% CI −327.2 to −24.3) with a trend after 12 months (−146.5 mm2, 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.

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  • Funding Funding is provided by Novartis Pharmaceuticals Australia; Australian Government; National Health and Medical Research Council; and Osteoporosis Australia. LLL is supported by an Australian Government Australian Postgraduate Award. DAD is supported by a Tasmanian Postgraduate Research Scholarship and a Heald Fellowship from Arthritis Australia. GJ is supported by a National Health and Medical Research Council practitioner fellowship. TMW is supported by an Osteoporosis Australia/Australian and New Zealand Bone and Mineral Society/Amgen Fellowship.

  • Competing interests GJ has participated in advisory boards, given talks and acted as a clinical investigator for Novartis.

  • Ethics approval Tasmanian Human Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.