Abstract: Purposes: Platelet-rich plasma (PRP) and stem cell treatments are commonly used for the treatment of osteoarthritis (OA). Studies of these treatments are often criticized due to lack of a control group. However, controlled studies are both prohibitively expensive and resisted by patients. There are numerous controlled studies of hyaluronic acid and other injectates that report detailed characteristics of their placebo arms in which saline was injected. The accumulated data from these placebo arms can serve as a historical control. Our objective was to characterize the magnitude and duration of this placebo/saline effect for the purpose of providing a control group against which the effects of knee injection can be measured in single armed OA knee injection studies without control groups.
Methods: We performed a comprehensive search of the MEDLINE database for randomized clinical trials in adult humans of an injective therapy for osteoarthritis of the knee which included injection of ‘normal’ or physiological saline (0.9% NaCl) as a placebo cohort. Included studies reported results to at least 3 months post-injection using either a visual analog scale for pain (VAS) and/or a WOMAC total score (the Western Ontario and McMaster Universities Osteoarthritis Index). Studies were excluded if the injective therapy was paired with additional intervention including physical therapy and surgical procedures. Mean scores were calculated for pre-treatment and at 3 months and 6 months post treatment. Reported scores at other intervals were noted for secondary review.
Results: 33 study arms met the criteria of which 24 reported WOMAC total scores and 19 reported VAS scores. The mean change in WOMAC scores peaked at 1-3 weeks, then declined below or near the minimal clinically important difference (MCID) by 12 weeks. The mean VAS scores similarly peaked at 1-3 weeks but never exceeded MCID at any time point.
Conclusions: The normal saline therapeutic effect for knee injection for OA is small, peaks early, is short-lived and relatively consistent among studies. It can provide a useful valid control group against which to measure the therapeutic effects of single armed knee injection studies of PRP, stem cell or other injection treatments for osteoarthritis.
