Intra-articular injection of platelet-rich plasma (PRP) has been established as a suitable treatment for knee osteoarthritis. Here, we present a double-blind randomized controlled clinical trial, conducted in a public Hospital of the Spanish National Health Care System, to evaluate the efficacy of injecting autologous PRP versus hyaluronic acid (HA) in knee osteoarthritis. PRP was manufactured in Malaga’s Regional Blood Center (Spain). Patients that met the eligibility criteria were randomized into a PRP group or a HA group. Pain and functional improvements were assessed pre- and post-treatment (three and six months follow-up) using the Visual Analogue Scale (VAS); the Knee and Osteoarthritis Outcome System (KOOS) scale and the European Quality of Life scale (EUROQOL). Both groups presented pain reduction at six months. The VAS scores for the PRP group improved by at least 50% from their initial value, particularly at three months following the final infiltration, with results resembling those of the HA group at six months. PRP was more effective in patients with lower osteoarthritis grades. Both treatments improved pain in knee osteoarthritis patients without statistically significant differences between them. However, PRP injection was proved to improve pain three months after the final infiltration and to be more effective in lower osteoarthritis grades.


The increase in average life expectancy and the high incidence of knee arthritis has led to a search for less aggressive alternatives to joint replacement with a lower financial impact on the health system. Some novel strategies are based on stimulation methods for cartilage repair or for the inhibition of catabolic enzymes, gene therapy, artificial replacement cartilage and the use of growth factors. Platelet-rich plasma (PRP) is a natural concentrate of autologous growth factors obtained through centrifugation of a patient’s own blood. PRP is obtained at a low cost and in a simple and minimally invasive manner using an “open technique” in blood banks or through a “closed technique” using disposable commercial kits. Bioactive cytokines and proteins from the platelet’s alpha granules induce chemotaxis, cellular migration, proliferation, differentiation and extracellular matrix production [1]. In addition, these proteins increase the release of angiogenic growth factors [2,3] contributing to tissue regeneration and cicatrisation [4]. The main growth factors contained in PRP are platelet-derived growth factor (PDGF), transforming growth factor (TGF ), insulin-like growth factor (IGF-1) and fibroblast growth factor (FGF). Interestingly, these factors have been proved to be involved in chondrogenesis and cartilage regeneration [5,6]. Local infiltration of PRP, extensively studied in maxillofacial pathology [7,8], has achieved good results in soft tissue injuries [9,10]. Although the regenerating potential and role of PRP in stabilizing angiogenesis in arthritic knees has been recognized [2,11], its use in articular pathology has not yet been sufficiently supported by controlled studies. In fact, the hypothesis that PRP reduces pain has been argued by several studies [12–14]. Nevertheless, when pain persists after oral anti-inflammatory or analgesic medications the intra-articular injections of corticosteroids (CS), hyaluronic acid (HA) and platelet-rich plasma (PRP) is indicated before a surgical treatment is performed [15,16]. A revision of the conducted clinical trials evidence that intra acicular injections of HA may be useful in patients with knee osteoarthritis (OA). They are characterised by delayed onset, but prolonged duration of symptomatic benefit, such as improvements in pain on weight bearing, when compared to injections of corticosteroids [16]. A recent clinical study conducted by Sánchez and Anitúa et al. [17] concluded that PRP manufactured in a closed system designed and commercialized by the authors was shown to be more efficient in controlling pain than HA treatment. The Spanish Agency of Medicines and Medical Devices (AEMPS) [18] has considered that the product known as PRP, obtained by blood centrifugation, is neither a hemo- derivative nor a biological product, but a medicine for human use. As such, PRP must be manufactured and supplied. AEMPS established that obtaining and processing this product must follow the standard quality-control measures for blood-derived products. Some authors indicate the need of more independent, prospective, randomized and controlled studies before PRP infiltration can be accepted into current practice [19–21]. In this respect, we present the first clinical trial performed under the directives of the AEMPS to test the efficacy of PRP infiltration to treat arthritic knees. The initial hypothesis of the present study was that patients would get improved OA treatments if a close relationship between two health public centres were established. To test so, the main objective of the present study was to determine the efficacy of a clinic protocol developed in public healthcare centres that allow patients to benefit from the analgesic power of their own plasma, obtained from just a single puncture, processed in accordance with the safety regulations established by AEMPS.


Based on the selection criteria (Table 1), 55 patients were chosen for this study and later randomized into a PRP group (n = 28) (group I) or a HA group (n = 27) (group II). One patient from group I was excluded by impossibility of venepuncture and one patient from group II needed arthroscopic surgery, and thus 27 patients in group I and 26 patients in group II completed the trial (Figure 1).

Full Article: Intra-Articular Injections of Platelet-Rich Plasma versus Hyaluronic Acid in the Treatment of Osteoarthritic Knee Pain: A Randomized Clinical Trial in the Context of the Spanish National Health Care System