ABSTRACT: Objectives:Viscosupplementation with new-generation, polyol-containing, cross-linked hyaluronic acid (HA) gels reduces joint inflammation in patients with knee osteoarthritis. Gait analysis is a complementary outcome measure to standard patient-reported scores and physical measures for testing the effect of HA injection. This three-arm, prospective, randomized, controlled, double-blind, feasibility pilot study investigated which gait parameters are more sensitive following a single bolus injection of polyol-containing HA for knee osteoarthritis. Methods:Twenty-two patients with Ahlbäck grade II-III knee osteoarthritis were randomly allocated into three groups: (1) HA?+?mannitol (n?=?9), (2) HA?+?sorbitol (n?=?5), and (3) saline placebo (n?=?8). Patients were assessed by blinded observers prior to injection and at 4?weeks post-injection (4W). Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Society score (KSS), EuroQol in five-dimensions (EQ-5D), VAS pain, and VAS stiffness. Gait was assessed over 30?m using a portable inertial-based data logger (Physilog®). Results:Differences between 4W and baseline were statistically significant for the mannitol-containing viscosupplement, with a median increase of 0.076?m/s on gait speed (p?=?0.039), 0.055?m on stride length (p?=?0.027), and 15 points on the KSS (p?=?0.047). In contrast, the HA?+?sorbitol and saline groups demonstrated no significant changes from baseline to 4W in any gait parameters or self-reported outcome measures (all p?>?0.3). The observed increase in gait speed is approximately 13% greater than the mean difference between healthy subjects and those with knee osteoarthritis, is clinically important, and thus is a sensitive gait parameter. Conclusions:This study demonstrated gait speed and stride length are the most relevant gait parameters to investigate when assessing the effect of polyol-containing HA viscosupplementation. This study supports the need for a larger, randomized, controlled, clinical trial to assess the effect of a single-bolus HA injection versus multiple injections in people with knee osteoarthritis using both gait performance and self-reported parameters of knee function. Trial registration:This study was retrospectively registered at clinicaltrials.gov on August 20, 2018, and assigned #NCT03636971. Level of evidence:I.
