Zoledronic acid plus methylprednisolone versus zoledronic acid or placebo in symptomatic knee osteoarthritis: a randomized controlled trial

Guoqi Cai, Laura L. Laslett, Dawn Aitken, Flavia Cicuttini, Lyn March, Catherine Hill, Tania Winzenberg, Graeme Jones

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)


Background: The aim of this study was to compare the efficacy and safety of zoledronic acid (ZA) plus intravenous methylprednisolone (VOLT01) to ZA, and placebo for knee osteoarthritis. Methods: A single-center, double-blind, randomized controlled trial (RCT) was carried out. Adults (aged ⩾50 years) with knee osteoarthritis, significant knee pain [⩾40 mm on a 100 mm visual analog scale (VAS)], and magnetic resonance imaging-detected bone marrow lesion (BML) were randomized to receive a one-off administration of VOLT01, ZA, or placebo. The primary hypothesis was that VOLT01 was superior to ZA in having a lower incidence of acute phase responses (APRs) over 3 days. Secondary hypotheses were that VOLT01 was noninferior to ZA, and both treatments were superior to placebo in decreasing BML size over 6 months and in improving knee pain [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and VAS] and function (WOMAC) over 3 and 6 months. Results: A total of 117 patients (62.2 ± 8.1 years, 63 women) were enrolled. The incidence of APRs was similar in the VOLT01 (90%) and ZA (87%) groups (p = 0.74). VOLT01 was superior to ZA in improving knee pain and function after 6 months and noninferior to ZA in reducing BML size. However, BML size change was small in all groups and there were no between-group differences. Compared with placebo, VOLT01 but not ZA improved knee function and showed a trend toward improving knee pain after 6 months. Conclusions: Administering intravenous methylprednisolone with ZA did not reduce APRs or change knee BML size over 6 months, but in contrast to ZA or placebo, it may have a beneficial effect on symptoms in knee osteoarthritis. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000039785.

Original languageEnglish
Article number1759720X19880054
Number of pages12
JournalTherapeutic Advances in Musculoskeletal Disease
Publication statusPublished - 23 Oct 2019


  • acute phase response
  • bone marrow lesion
  • methylprednisolone
  • noninferiority
  • zoledronic acid

Cite this