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      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

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          Abstract

          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.

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          Most cited references38

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          OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines.

          To develop concise, patient-focussed, up to date, evidence-based, expert consensus recommendations for the management of hip and knee osteoarthritis (OA), which are adaptable and designed to assist physicians and allied health care professionals in general and specialist practise throughout the world. Sixteen experts from four medical disciplines (primary care, rheumatology, orthopaedics and evidence-based medicine), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. A systematic review of existing guidelines for the management of hip and knee OA published between 1945 and January 2006 was undertaken using the validated appraisal of guidelines research and evaluation (AGREE) instrument. A core set of management modalities was generated based on the agreement between guidelines. Evidence before 2002 was based on a systematic review conducted by European League Against Rheumatism and evidence after 2002 was updated using MEDLINE, EMBASE, CINAHL, AMED, the Cochrane Library and HTA reports. The quality of evidence was evaluated, and where possible, effect size (ES), number needed to treat, relative risk or odds ratio and cost per quality-adjusted life years gained were estimated. Consensus recommendations were produced following a Delphi exercise and the strength of recommendation (SOR) for propositions relating to each modality was determined using a visual analogue scale. Twenty-three treatment guidelines for the management of hip and knee OA were identified from the literature search, including six opinion-based, five evidence-based and 12 based on both expert opinion and research evidence. Twenty out of 51 treatment modalities addressed by these guidelines were universally recommended. ES for pain relief varied from treatment to treatment. Overall there was no statistically significant difference between non-pharmacological therapies [0.25, 95% confidence interval (CI) 0.16, 0.34] and pharmacological therapies (ES=0.39, 95% CI 0.31, 0.47). Following feedback from Osteoarthritis Research International members on the draft guidelines and six Delphi rounds consensus was reached on 25 carefully worded recommendations. Optimal management of patients with OA hip or knee requires a combination of non-pharmacological and pharmacological modalities of therapy. Recommendations cover the use of 12 non-pharmacological modalities: education and self-management, regular telephone contact, referral to a physical therapist, aerobic, muscle strengthening and water-based exercises, weight reduction, walking aids, knee braces, footwear and insoles, thermal modalities, transcutaneous electrical nerve stimulation and acupuncture. Eight recommendations cover pharmacological modalities of treatment including acetaminophen, cyclooxygenase-2 (COX-2) non-selective and selective oral non-steroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs and capsaicin, intra-articular injections of corticosteroids and hyaluronates, glucosamine and/or chondroitin sulphate for symptom relief; glucosamine sulphate, chondroitin sulphate and diacerein for possible structure-modifying effects and the use of opioid analgesics for the treatment of refractory pain. There are recommendations covering five surgical modalities: total joint replacements, unicompartmental knee replacement, osteotomy and joint preserving surgical procedures; joint lavage and arthroscopic debridement in knee OA, and joint fusion as a salvage procedure when joint replacement had failed. Strengths of recommendation and 95% CIs are provided. Twenty-five carefully worded recommendations have been generated based on a critical appraisal of existing guidelines, a systematic review of research evidence and the consensus opinions of an international, multidisciplinary group of experts. The recommendations may be adapted for use in different countries or regions according to the availability of treatment modalities and SOR for each modality of therapy. These recommendations will be revised regularly following systematic review of new research evidence as this becomes available.
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            Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration.

            This study analyzed the effect of the platelet count in platelet-rich plasma (PRP) on bone regeneration in vivo. Twenty male New Zealand white rabbits were used. PRP was produced using the Platelet Concentrate Collection System (PCCS) (3i, Miami, FL, USA). After inducing ketamine-xylazine anaesthesia, a self-tapping titanium screw (Branemark MK III TiUnite, 3.75 x 7 mm) was inserted in each distal femur; the femurs were randomized so that one side was treated with PRP while the other (control) was not. Intravital fluorochrome staining was performed on days 1, 7 (1.5 ml of 2% doxycycline/kg bodyweight), 14 (6% xylenol orange, 1.5 ml/kg), and 21 (1% calcein green, 5 ml/kg). Animals were euthanized on day 28 (n = 20). Specimens were prepared for histomorphological evaluation according to Donath and Breuner [J. Oral Pathol. 11 (1982) 318]. Comparing the bone regeneration (fluorochrome staining) in the 4-week implants (n = 19), the only significant difference (sign test, P = 0.004) was seen with intermediate platelet concentrations (n = 9,503,000-1,729,000 platelets/microl PRP). There were no differences in the bone/implant contact rates between the test and the control side among the three groups. The platelet concentration required for a positive PRP effect on bone regeneration seems to span a very limited range. Advantageous biological effects seem to occur when PRP with a platelet concentration of approximately 1,000,000/microl is used. At lower concentrations, the effect is suboptimal, while higher concentrations might have a paradoxically inhibitory effect. On the other hand, the effect of this type of platelet concentrate was not beneficial to accelerate the osseointegration of enosseous dental implants.
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              The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery: a review of the literature.

              Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet alpha granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-beta, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches. The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research.

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                02 July 2016
                July 2016
                : 17
                : 7
                : 1064
                Affiliations
                [1 ]Department of Orthopedic Surgery and Traumatology, Virgen de la Victoria University Hospital, Málaga E-29010, Spain; sofiairizar@ 123456gmail.com (S.I.); pedrojhuertascot@ 123456hotmail.com (P.J.H.)
                [2 ]Department of Anestesiology. Pain’s Treatment Unit. Virgen de la Victoria University Hospital, MálagaE-29010, Spain; espeotero@ 123456hotmail.com (E.O.); martadelvalle75@ 123456hotmail.com (M.d.V.)
                [3 ]Málaga Tissue Bank, Regional Blood Center, Málaga E-29009, Spain; isidro.prat.sspa@ 123456juntadeandalucia.es (I.P.); macarenas.diaz.sspa@ 123456juntadeandalucia.es (M.S.D.-G.); carmen.hernandez.lamas.sspa@ 123456juntadeandalucia.es (M.d.C.H.-L.)
                [4 ]Department of Health Sciences, University of Jaén, Jaén E-23071, Spain; mperan@ 123456ujaen.es
                [5 ]Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada E-18071, Spain; jmarchal@ 123456ugr.es
                [6 ]Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada E-18016, Spain
                [7 ]Biosanitary Institute of Granada (ibs. GRANADA), University Hospitals of Granada-University of Granada, Granada, Granada E-18016, Spain
                Author notes
                [* ]Correspondence: elvira0511@ 123456gmail.com ; Tel.: +34-951-032-000; Fax: +34-951-032-022
                Article
                ijms-17-01064
                10.3390/ijms17071064
                4964440
                27384560
                e731ad2f-44c2-4d07-a463-c56e3c85af5d
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 April 2016
                : 23 June 2016
                Categories
                Article

                Molecular biology
                platelet-rich plasma,knee osteoarthritis,clinical trial,hyaluronic acid
                Molecular biology
                platelet-rich plasma, knee osteoarthritis, clinical trial, hyaluronic acid

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