Reply to the Letter to the Editor: Does the Combination of Platelet-rich Plasma and Supervised Exercise Yield Better Pain Relief and Enhanced Function in Knee Osteoarthritis? A Randomized Controlled Trial

To the Editor,

We read the letter to the editor by Han et al. [8] and appreciate the authors’ interest in our recent manuscript, “Does the Combination of Platelet-rich Plasma and Supervised Exercise Yield Better Pain Relief and Enhanced Function in Knee Osteoarthritis? A Randomized Controlled Trial” [9]. We would like to thank CORR® for the opportunity to respond.

First, the authors note that no clear information was provided regarding the use of oral analgesics. In our study, participants were not permitted to take any oral analgesics, NSAIDs, or oral steroids, regardless of their group allocation. However, one participant who used NSAIDs (n = 1) was excluded from the study, according to our prespecified exclusion criteria, as was shown in the flow chart in our original paper. Because of word count limitations, not all diseases or conditions covered by these criteria were listed individually. Among our exclusion criteria was “previous invasive procedure,” which encompassed “stem cell therapy and blood product therapy”; another was “platelet count lower than 150 x 10³/µL,” which may have been relevant to the concerns of Han et al. [8]. Additionally, the exclusion criterion “systemic disorders” included “rheumatic diseases and bleeding disorders.”

Second, the authors [8] pointed out that “details on all the key variables required for PRP [platelet-rich plasma] processing” were missing from our paper. Although supplementary material concerning these data exist, the supplemental materials were not published when our original paper was published online ahead of print, as was our intention. This information is now available as an online appendix [9] (Supplemental Tables 1-3; https://links.lww.com/CORR/B310).

Third, since the letter provided no reference, we were unable to confirm the suggestion that a platelet count at least five times higher than the initial count is required for PRP treatment. By contrast, many studies on this topic [1-4, 6, 7, 10, 13] have indicated that the requisite rise in platelet count in PRP, compared to the mean platelet count in whole blood, may range from 1.6 to 8 times. As far as we know, no study has directly demonstrated superior clinical efficacy associated with higher platelet concentrations. Furthermore, perspectives exist that suggest increases exceeding six-fold could yield inhibitory effects [11, 16]. Because of the lack of consensus on this matter, the contention that a 3.4-fold increase is inadequate (dose: 4.04 x 10¹² µL injected platelets, meeting Marx’s definition [12]) lacks empirical grounding.

Finally, the “historical study” from 2017 [15] that the authors mentioned reported that PRP exhibited greater efficacy than hyaluronic acid and saline based on WOMAC scores. However, this reference alone is insufficient to substantiate such a claim. In response, leading journals in the field have published meta-analyses [5, 14] indicating that PRP does not display superiority over alternative knee osteoarthritis treatments. Consequently, there is a recognized need for high-quality studies. Our study is among those dedicated to addressing this research gap.