Intra-articular normal saline (IA-NS) injections have been utilized as a placebo in a number of randomized controlled trials pertaining to the management of knee osteoarthritis (OA); however, it is believed that these "placebo" injections may have a therapeutic effect that has not been quantified in the literature.
To (1) quantify the effect of IA-NS injections on patient-reported outcomes (PROs) and (2) compare postinjection PROs to established minimal clinically important difference (MCID) criteria to demonstrate a potential therapeutic effect.
Meta-analysis.
A review was conducted to identify all randomized, placebo-controlled trials on injection therapy for knee OA between 2006 and 2016. Patient demographics and PROs before the injection and at 3 and 6 months after the injection were collected for patients in the IA-NS injection group in each study. A random-effects model was used to compare preinjection scores and scores at each postinjection time point in a pairwise fashion.
In total, there were 14 placebo cohorts in 13 studies that were analyzed after meeting inclusion criteria for this meta-analysis. This included 1076 patients (Kellgren-Lawrence grade 1-4), with a weighted mean age of 62.53 years and mean body mass index of 28.67 kg/m
The administration of an IA-NS placebo injection yields a statistically and clinically meaningful improvement in PROs up to 6 months after the injection in patients with knee OA. This observation supports the notion that the so-called placebo effect for IA-NS injections achieves a clinically meaningful response in patients with OA when provided during comparison studies to an active treatment group (ie, hyaluronic acid).