Summary

This project evaluates orthobiologic augmentation of hyaluronic acid injections as a pain management tool and provides evidence that viscosupplementation injections augmented with orthobiologics are a promising treatment option.

Abstract

Introduction

Hyaluronic acid (HA) injections are a promising, minimally invasive treatment option for joint pain, but do not provide prolonged pain relief. The purpose of this study was to assess the effects of intra-articular HA and platelet rich plasma (PRP) injections on pain with and without Amniotic Fluid products (Amnio). All injections containing Amnio were performed before the FDA’s halt on the use of amniotic products in 2021.We hypothesized that these intra-articular knee injections would produce a decrease in patient reported outcomes (PROMs) of knee pain.

Methods

A total of n=360 intra-articular knee joint injections were administered under IRB approval (Salus IRB No. 10008) from 05/24/2012 to 05/06/2024. Treatment groups consisted of HA+PRP (n=245) and HA+PRP+Amnio (n=115). Of these injections, n=157 were administered to treat OA-associated pain. Visual Analog Pain Scale (VAS) at rest, with activity, and at night was measured in patients at the following intervals: baseline, 1-, 3-, 6-, and 12-months status-post injection. Measures of statistical significance with respect to each group’s own baseline were obtained by two-tailed t-test and Cohen’s D effect sizes were calculated to reveal any clinical relevance at a threshold of +/-0.20.

Results

HA+PRP injections provided a statistically significant (p<0.001) decrease in Pain with Activity (1, 3, 6, and 12 mos.), whereas decreases in Pain at Rest (6 mos.) and Pain with Activity (6 and 12 mos.) were observed with HA+PRP+Amnio injections. Additionally, Cohen’s D effect sizes revealed clinically relevant decreased Pain at Rest (3 and 12 mos.), Pain with Activity (1, 3, 6, and 12 mos.), and Pain at Night (1, 3, and 12 mos.) in the HA+PRP group. HA+PRP+Amnio demonstrated clinically relevant decreases in Pain at Rest (3, 6, and 12 mos.), Pain with Activity (1, 3, 6, and 12 mos.), and Pain at Night (3, 6, and 12 mos.).

Discussion

Persistent pain relief months after an injection of HA+PRP or HA+PRP+Amnio represents an improvement and important benefit to patients. Historically, HA injections have shown peak pain relief at 8 weeks, with residual effects up to 24 weeks from injection. This investigation establishes that orthobiologic-augmented injections could improve outcomes of viscosupplementation alone. Prior investigations by our group revealed increased HA production with Amnio injections, which is a potential explanation for the prolonged, improved outcomes observed in this study. Based on these findings, further investigation of orthobiologics as a pain management modality is warranted. However, FDA bans on the clinical use of amniotic-derived products for non-approved indications prevents further study of these products.