The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis

Abstract

BackgroundIntra-articular hyaluronic acid (IA-HA) is a common therapy used to treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), typically prescribed in regimens ranging from a single injection to 5 weekly injections given once weekly. We conducted a systematic review to determine the efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain and adverse events (AEs) across different dosing regimens.MethodsWe conducted a systematic search of the literature to identify studies evaluating IA-HA for the management of knee OA compared to IA-saline. Primary outcome measure was the mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary outcome was the number of treatment-related AEs and treatment-related serious adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs between dosing regimens compared to IA-Saline.ResultsThirty articles were included. Overall, IA-HA injections were associated with less knee pain compared to IA-Saline injections for all dosing regimens. 2–4 injections of IA-HA vs. IA-Saline produced the largest effect size at both 3-months and 6-months (Standard mean difference [SMD] = −0.76; −0.98 to −0.53, 95% CI, P < 0.00001, and SMD = −0.36; −0.63 to −0.09 95% CI, P = 0.008, respectively). Additionally, single injection studies yielded a non-significant treatment effect at 3 and 6 months, while ≥5 5 injections demonstrated a significant improvement in pain only at 6 months. Five or more injections of IA-HA were associated with a higher risk of treatment-related AEs compared to IA-Saline (Risk ratio [RR] = 1.67; 1.09 to 2.56 95% CI, p = 0.02), which was a result not seen within the 1 and 2–4 injection subgroups.ConclusionOverall, 2–4 and ≥5 injection regimens provided pain relief over IA-Saline, while single injection did not. Intra-articular injections of HA used in a 2–4 injection treatment regimen provided the greatest benefit when compared to IA-Saline with respect to pain improvement in patients with knee OA, and was generally deemed safe with few to no treatment-related AEs reported across studies. Future research is needed to directly compare these treatment regimens.Electronic supplementary materialThe online version of this article (10.1186/s12891-017-1897-2) contains supplementary material, which is available to authorized users.

Effects of intra‐articular hyaluronic acid associated to Chitlac (arty‐duo®) in a rat knee osteoarthritis model

“…However, when lifestyle modification, physical therapy, and nonsteroidal anti‐inflammatory drugs lack to allay OA symptoms, intra‐articular (i.a.) hyaluronic acid (HA) injections are frequently used . Various physiological effects contribute to the mechanisms by which viscosupplementation with HA exerts its clinical and chondroprotective effect: increases the proteoglycan synthesis, reduces the production and activity of soluble pro‐inflammatory mediators and degradative enzymes (e.g., matrix metalloproteinases, MMP) and alters the behavior of immune cells .…”

“…hyaluronic acid (HA) injections are frequently used. [6][7][8][9] Various physiological effects contribute to the mechanisms by which viscosupplementation with HA exerts its clinical and chondroprotective effect: increases the proteoglycan synthesis, reduces the production and activity of soluble proinflammatory mediators and degradative enzymes (e.g., matrix metalloproteinases, MMP) and alters the behavior of immune cells. 10 HA has also shown an antioxidant effect in various systems, thus providing protection to joint chondrocytes against oxygen-induced free radical damage.…”

Efficacy of single high-molecular-weight versus triple low-molecular-weight hyaluronic acid intra-articular injection among knee osteoarthritis patients

“…In the meta-analysis conducted by Concoff et al, [34] the e cacy of multiple HA injections versus a single dose of HA was studied. The pooled data showed that a single HA injection was not signi cantly more effective than IA-Saline in a period of six months.…”

“…In a few studies the e cacy of single cross-linked HMW-HA has been investigated, though there exists a discrepancy between them. [33][34][35][36] Our utilized HMW-HA (Arthromac®, Novatex Bioengineering SA Switzerland) is one of these cross-linked products which is indicated for single intra-articular injection in knee OA patients. [37] The aim of current trial was to compare the e cacy and safety of the single cross-linked HMW injection versus triple injection of low-molecular-weight IA-HA among knee OA patients in terms of function and pain improvement during a six-month period.…”

Periodic Curcumin Monoglucuronide Injections Ameliorate Structural Osteoarthritis Changes in Rats with Destabilized Medial Meniscus

“…Osteoarthritis (OA) is a progressive disease that affects the activity of daily living in many people worldwide. Conservative treatments for OA include physiotherapy [1,2], dieting [3,4], hyaluronic acid intra-articular injection [5], and non-steroidal anti-in ammatory drugs (NSAIDs) [6], and they have certain bene cial effects. However, it is di cult to prevent OA progression, while analgesic drugs such as NSAIDs have adverse effects [7,8].…”