# The Role of Platelet-Rich Plasma in the Management of Ankle Osteoarthritis: A Systematic Review
## 4 Discussion  
PRP has gained popularity in the treatment of large joint OA due to its relative simplicity and acceptable cost when compared to other invasive procedures. In most cases, the promising results pertaining to this innovative approach derive from clinical studies with a limited scientific background [11; 24; 25]. Several animal studies have shown that intraarticular PRP injections can promote cartilage regeneration by enhancing chondrogenic differentiation, inhibiting chondral degeneration, and decreasing synovial inflammation. Thus, PRP is theorized to act in OA joints through cytokines, chemokines, and growth factors that inhibit the destruction of hyaline cartilage, or even regenerate it [24]. This work provides a comprehensive review of the effectiveness of PRP for the treatment of ankle OA. There have been only five published studies on using PRP for this condition. During the eligibility phase, two studies were excluded, since the subjects suffered from osteochondral lesions and were not strictly diagnosed with ankle OA. Another study was also excluded because the injection techniques did not consider the PRP modality. The quality of the evidence of the selected studies was low, as the majority were level IV, whereas bias in the selection of participants in the studies was identified as the most common type of bias. The results of this systematic review thus provide level IV evidence that injection of PRP seems effective in short follow-ups in patients with different stages of ankle OA. These reported positive results should be considered in the context of the studies' inherent methodological limitations, their variable reporting characteristics, and the natural course of ankle OA. Therefore, the generalization of these findings is limited by the weakness of the selected studies. Limited data are thus available to confirm that current PRP therapy is effective as postulated. Moreover, there is growing interest in the biological mechanisms behind PRP injections and, more importantly, in how to modulate these processes for beneficial functional and clinical effects. Despite the small number of included studies, our review has confirmed the wide variation in reported preparation procedures for PRP, as the scientific literature reflects [25; 26; 27]. Each factor pertaining to the preparation procedure may represent a source of variation that can influence the effectiveness of the final product. Platelet viability and the number of released growth factors and cytokines are dependent on the length of time for each spin cycle and the centrifugal acceleration parameters. Given these already known data, the standardization of platelet-obtaining methodology is essential to ensure a comparable grade of growth factor release. All the included studies in this review employed a different type of PRP based on the preparation method (single, double, or triple centrifugation) and cellular component (the concentration of platelets and the presence of red cells). One of the selected studies chose to include red cells in the PRP [20], while the other two studies elected to exclude them [21; 22]. Furthermore, it is important to highlight the variation in the platelet concentration, as it is presumably a critical aspect of the regeneration process. The number of injections and the site of administration varied among the included investigations as well. [PERSON] et al. and [PERSON] et al. treated their patients with only one injection of PRP [22; 23], whereas [PERSON] et al. employed two applications, with one injection every 6 weeks [19]. The other proposals included at least three injections administered once every week/two weeks [20; 21]. All the included studies reported intraarticular administration, except for the study by [PERSON] et al., who injected the perilesional area under US/fluoroscopy guidance [22]. However, the severity of ankle OA did not significantly differ among the papers.