Abstract
We thank Isabel Andia and the scientific board of the Groupe de Recherche Internationale sur les Injections de Plaquettes (GRIIP) for their important work in the field of orthobiologics and for their interest in and appreciation of our study, which provided important insights into the complexity of platelet-rich plasma (PRP) research. We also thank them for their comments, which allowed us to clarify some points and better underline others. Our study evaluated the influence of leukocyte and platelet concentrations on PRP clinical efficacy by analyzing >250 patients with knee osteoarthritis (OA) who were treated with PRP injections in the same institution by the same orthopaedic team. Although we acknowledge the retrospective nature of the study, we also underline that we used prospectively collected data of consecutive patients treated within our research center in the past years. Moreover, the data set included only patients treated in high-level studies with clear selection criteria and management from the same team specialized in such studies, thus representing a large body of valuable data for the purpose of this study, despite the retrospective nature of the analysis and in light of the scarce data available in the field to directly address the study question.
Research in the last decade has focused on the role of leukocytes, possibly neglecting other important factors. Although our study found no influence of leukocyte concentration, confirming the results of recent high-level evidence reporting no significant impact of leukocytes,3,4 interesting findings regarding platelet concentration were documented. The univariate analysis documented a positive correlation between platelet concentration and clinical scores at all follow-up evaluations, with higher platelet concentrations leading to higher clinical improvements, suggesting a key role of platelets in the efficacy of PRP. 2 This result was confirmed by the stratification of patients into 3 groups based on PRP platelet concentration; the group receiving high platelet concentration had the best clinical result, whereas patients receiving low platelet concentration exhibited less satisfactory clinical outcomes and higher rate of clinical failure.
Because several factors related to both PRP and patient characteristics could affect the clinical outcome after PRP injections, we performed univariate analyses exploring clinical scores and the variables analyzed in this study, such as leukocyte concentration, age, sex, body mass index, and Kellgren-Lawrence score, without finding a correlation with clinical improvement. Platelets were the only variable that correlated with the clinical outcome. To address the letter by Andia and colleagues, we used a multivariate model to further analyze how patient characteristics, such as age, sex, body mass index, and Kellgren-Lawrence score, and PRP characteristics such as leukocyte concentration and platelet concentration influenced the improvement of the International Knee Documentation Committee subjective score from baseline to 6 months, a time that is often considered the most suitable to investigate the effects of injection. The multivariate analysis confirmed the results of the previous univariate analysis. The only factor that influenced clinical improvement was PRP platelet concentration (P = .036; partial η2 = 0.018). In contrast, patient characteristics such as age (P = .561), sex (P = .675), body mass index (P = .597), and Kellgren-Lawrence score (P = .461), as well as leukocyte concentration (P = .495), were not shown to influence patient outcome in this series.
The results of this study shed new light on the use of PRP and could explain some controversial literature findings on the potential of this orthobiologic approach for patients with knee OA. During the last decade, much attention has been placed on the presence of leukocytes in PRP; however, this study indicated that the effects of leukocytes shown in vitro may not be translated into clinically perceptible differences after PRP injections. Thus, the focus should be broadened to include the role of platelet concentration, as this study suggested the importance of this PRP factor in terms of clinical efficacy. Further evidence showing a role of platelet concentration emerged from a recent meta-analysis that indirectly compared the clinical results offered by PRP with different platelet concentrations in patients with knee OA by analyzing 18 randomized controlled trials. 1 The meta-analysis found that studies using PRP formulations with higher platelet concentrations demonstrated superior pain relief and more durable functional improvement compared with studies on PRP with lower platelet concentrations. In light of these results, further studies are needed regarding platelet concentration and platelet dose in order to optimize the use of PRP in orthopaedic clinical practice.
Our study was not intended to draw definitive conclusions on this matter. Many aspects, within Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO) and beyond MIBO parameters, can play a role and should be investigated. Future large, randomized studies with direct PRP comparisons are needed to confirm the benefit offered by PRP with high platelet concentration versus low platelet concentration. Considering the recent findings, we hope that other centers will become more active in this direction by developing high-level studies focused on the number of platelets, offering a new perspective for future PRP investigations to optimize the clinical management of knee OA.
Footnotes
One or more of the authors has declared the following potential conflict of interest or source of funding: S.Z. reports grants from Fidia Farmaceutici SpA, Cartiheal Ltd, Igea Clinical Biophysics, Biomet, and Kensey Nash. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
