Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee- Letter to the Editor & Author Response.

Letter to the Editor

Patel S1, Dhillon MS1, Bansal T1

Dear Editor,

We read with great interest the article published online in your journal on 3rd August 2016 by Lana et al entitled “Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee”.[. First of all we would like to congratulate the authors on a beautifully designed and well executed study. PRP and hyaluronic acid are at present the forerunners in the race for treatment of osteoarthritis. While many studies have highlighted their effects individually, this is one of the earliest to highlight their synergistic effect in OA knee in humans. Orthobiologics may now be the evolving modality in the treatment of osteoarthritis, and we believe this will certainly be the future of treatment of osteoarthritis. Nevertheless, we would like to clarify certain points, and present our point of view pertaining to the article.

The authors have used high molecular weight hyaluronic acid (2.4-3.6 MDa) in concentration of 10mg/ml, ie 1% w/v (Eufflexa-Ferring 10mg/ml HA) and HA has been used with PRP in the ratio of 1:2.5. We would like to question and get calrifications about the rationale behind using this combination. Were any studies done for arriving at this specific combination? It is pertinent to note that it has been highlighted by some in vitro studies that PRP exerts a pure dilution effect on HA. Therefore, dilution in a ratio greater than 1:1, and the use of concentration below 1% affects the rheological properties of HA and may not be suitable. It has also been shown that low molecular weight HA enhances the synergistic effects when used in combination with PRP, and that Low molecular weight HA is better than using High molecular weight HA[.

Secondly, we would like to project our belief that it would have been more logical to give PRP injections first, followed by HA injections in an interval of one month[. This would prevent PRP and HA from potentially interfering with each other, but would still provide a synergistic effect.

Another point of note is that the authors have not mentioned as to how they arrived at the sample size required for their randomized trial. They are requested to provide clarification as to to which primary parameter (VAS versus WOMAC) was used in sample size calculation. The sample size of the study seems inadequate for it to be labelled as an RCT as per CONSORT guidelines. Considering the absence of a true control group (Saline Placebo), and as both HA and PRP are established as treatment modalities in relieving pain in Knee OA, the sample size should have been larger to demonstrate a significant difference between the treatment groups.

We would also like the authors to shed some light on the randomization protocol that was followed. Despite randomization, the groups were skewed with the HA group demonstrating significantly more WOMAC pain score in the baseline analysis of the groups. This non homogenosity of data leads to serious questions regarding randomization method. On the other hand, this could be a result of the small sample size.

We would also like to point out that blinding of patients is an important issue; clarification is needed as to how blinding was achieved in subjects evaluated, as PRP preparation involves drawing of blood. Hence, blinding in the HA group would have been difficult, and needs to be clarified.

Based on the positive results of the present study and other in vitro studies, we are hopeful that combinations of HA and PRP will turn out to be an effective therapy for OA knee in the future. However, many more well designed randomized control trails, with larger sample sizes, are needed to determine the ideal dosing schedules and combinations.