Treatment with 4Jointz reduces knee pain over 12 weeks of treatment in patients with clinical knee osteoarthritis: a randomised controlled trial

Osteoarthritis Cartilage. 2012 Nov;20(11):1209-16. doi: 10.1016/j.joca.2012.07.019. Epub 2012 Aug 2.


Objective: To assess the efficacy of thrice daily topical 4Jointz utilizing Acteev technology (a combination of a standardized comfrey extract and a pharmaceutical grade tannic acid, 3.5 g/day) on osteoarthritic knee pain, markers of inflammation and cartilage breakdown over 12 weeks.

Patients and methods: Adults aged 50-80 years (n = 133) with clinical knee OA were randomised to receive 4Jointz or placebo in addition to existing medications. Pain and function were measured using a visual analogue scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) scale at baseline, 4, 8 and 12 weeks. Inflammation was measured analysing IL-6 expression and CTX-2 presence as representative for cartilage breakdown using ELISA, at baseline and 12 weeks.

Results: Pain scores significantly reduced in the group who received 4Jointz compared to the group who received placebo after 12 weeks using both the VAS (-9.9 mm, P = 0.034) and the KOOS pain scale (+5.7, P = 0.047). Changes in IL-6 and CTX-2 were not significant (-0.04, P = 0.5; -0.01, P = 0.68). Post-hoc analyses suggested that treatment may be most effective in women (VAS -16.8 mm, P = 0.008) and those with milder radiographic osteoarthritis (OA) (VAS -16.1 mm, P = 0.009). Rates of adverse events were similar in both groups, excepting local rash that was more common amongst participants receiving 4Jointz (21% vs 1.6%, IRR 13.2, P = 0.013), but only 26% (n = 4) of participants with rashes discontinued treatment. There were no changes in systemic blood results.

Conclusions: Topical treatment using 4Jointz reduced pain but had no effect on inflammation or cartilage breakdown over 12 weeks of treatment.

Trial registration: Australia and New Zealand Clinical Trials registry ACTRN12610000877088.

Publication types

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

MeSH terms

  • Administration, Topical
  • Aged
  • Aged, 80 and over
  • Analgesics / therapeutic use*
  • Comfrey / chemistry*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Knee Joint / physiopathology
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / complications
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / physiopathology
  • Pain / complications
  • Pain / drug therapy*
  • Pain / physiopathology
  • Pain Management
  • Pain Measurement
  • Plant Extracts / therapeutic use*
  • Recovery of Function
  • Tannins / therapeutic use*
  • Treatment Outcome


  • Analgesics
  • Drug Combinations
  • Plant Extracts
  • Tannins