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The Use of PRP Injections in the Management of Knee Osteoarthritis

The Use of PRP Injections in the Management of Knee Osteoarthritis

Abstract

Osteoarthritis (OA) is a common disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture that commonly affects the knee and/or hip joints. It is a major public health problem worldwide and is projected to rapidly increase as the population ages and the rates of obesity escalate. Autologous blood-derived products, such as platelet-rich plasma (PRP), are vital in tissue repair and regeneration and have important roles in fundamental processes, including inflammation, angiogenesis, cell migration and metabolism in pathological conditions, such as OA. PRP is a biological treatment option that is increasingly used in sports medicine applications. Outcomes from treating tendon, ligament, muscle, and cartilage injuries with PRP have shown variable results across many studies with the current evidence base for the efficacy of PRP in treating sports injuries remaining inconclusive. More uniformly positive results have been observed by various studies for PRP in OA knee in comparison to hyaluronic acid, other intra-articular injections and placebo than in other musculoskeletal tissue. However, methodological concerns as well as satisfactory PRP product classification prevent the true characterisation of this treatment. For knee OA management, these concerns must be addressed before this promising treatment can be widely implemented.

Introduction

Osteoarthritis (OA) is a serious degenerative joint disease resulting from the degradation of articular cartilage, degradation and proliferative reformation of subchondral bone and a low degree of synovitis that leads to a reduced quality of life (QoL). It is a major cause of pain and disability in the elderly population (>70 years) (Neogi and Zhang 2013). OA alters the normal joint metabolism favouring increased catabolism and decreased anabolism (Dhillon et al. 2017). Inflammation and vascular pathology, in combination with cell death, meniscal changes, bone remodelling and subchondral sclerosis, produces a vicious cycle of progressive joint degeneration. This can be exacerbated by excessive mechanical stress and oxidative damage (Wruck et al. 2011). Moreover, under conditions of metabolic or cytotoxic stress, such as in ageing, autophagy can be upregulated, further decompensating homeostatic mechanisms (Lotz and Caramés 2011).

In OA knees (Figure 1.), chondrocyte senescence and loss of cartilage integrity are major features. There is an increase in the water content of hyaline cartilage, accompanied by corresponding decreases in proteoglycan concentration, length and aggregation, causing reduced cartilage stiffness and fibrillation of the cartilage surface. From this, cartilage proceeds to erode and deep clefts may form. Concurrently, morphological changes in subchondral bone are found. As synovial fluid infiltrates, the formation of subarticular cysts in the subchondral bone also occurs. Osteophytes (bony projections) are characteristic features of knee OA in non-pressure areas, caused by the flattening of bone from pressure in high-wear areas (Adatia et al. 2012).

Many interacting factors have a role in indicating the potential for the development of knee OA, although age is typically highlighted (Blagojevic et al. 2010; Michael et al. 2010; Heidari 2011; Silverwood et al. 2015; Driban et al. 2017) (Table 1). Analysis of primary care databases of different countries found higher incidence of knee OA than hip or hand OA and a large increase in new knee OA diagnoses in the past decade, especially in 35-44 year olds (Prieto-Alhambra et al. 2014; Yu et al. 2015). Over a seven year period, an estimated 13% of older adults (>50 years) receive a diagnosis of OA with the knee joint implicated in twenty five percent of the population (Jordan et al. 2014). There is also an accompanying socioeconomic burden in terms of cost of medical care for both government and individuals (Xing et al. 2017). It is a major public health problem worldwide (Pereira et al. 2011) and is projected to rapidly increase as the population ages and rates of obesity escalate (Cross et al. 2014).

Hip and knee OA has been ranked as the 11th highest contributor to global disability and 38th highest in years lived with disability (Cross et al. 2014). The disability associated with knee OA results in a considerable economic burden, both in direct costs related to treatment, particularly joint replacement surgery, and job-related indirect costs, including loss of productivity (Murphy and Helmick 2012). Knee OA affects between 6% and 40% of the general population (Michael et al. 2010) and is significantly increased among retired elite athletes, with prevalence rates as high as 95% (Gouttebarge et al. 2015). The global burden of knee OA, as rated by the World Health Organisation (WHO – 2011), is comparable with that of patients with cardiac dysrhythmias, liver cirrhosis or stage IV kidney disease (Mather et al. 2013).

Current Knee Osteoarthritis Incidence and Management Strategies

Knee OA management strategies include improvement in function, reduction in disability, pain relief and hence, improved QoL (Ng et al. 2012; Xing et al. 2017). However, there currently exists no pharmacologic agents which are able to halt OA progression or to reverse existing damage (Kanchanatawan et al., 2016). Existing approaches focus on preventing or delaying progression by developing less invasive procedures or applying interventions earlier in the disease onset (Zhang et al. 2008). Non-operative therapeutic interventions involving intra-articular injection at the knee joint, including hyaluronic acid (HA), corticosteroids, platelet-rich plasma (PRP), non-steroidal anti-inflammatory drugs (NSAIDs), physical therapy and unloaded bracing, play major roles in the management of knee OA (Campbell et al. 2015).

Platelet Rich Plasma for inducing regeneration

PRP is an autologous mixture of highly concentrated platelets and associated growth factors and other bioactive components produced by centrifugal separation of whole blood (Figure 2) which is used in orthopaedic and sports medicine practices to treat bone, tendon and ligament injuries (Figure 3) (Sundman et al. 2014). The growth factors released by PRP have been discussed in great detail within the literature (Lubkowska et al. 2012; Pavlovic et al. 2016; Fernandes and Yang 2016; Parrish and Roides 2018) and have been shown to promote cell recruitment, proliferation, and angiogenesis resulting in a reduction in the critical regulators of the inflammatory process and a decrease in the expression of inflammatory enzymes (Table 2) (van Buul et al. 2011). PRP may induce a regenerative response by improving the metabolic functions of damaged structures (Ficek et al. 2011; Chen et al. 2018)and has been shown to have a positive effect on chondrogenesis and mesenchymal stem cell proliferation (Kabiri et al. 2014).

In clinical practice, PRP is used to enable the application of autologous plasma and platelet-derived proteins to a desired location with the use of an appropriate scaffold to assist in the repair of the injured tissue (Marx 2001). The rationale for PRP in scaffolds is to take advantage of the huge amount of growth factors contained in platelets to promote cartilage regeneration; however, the use of PRP-augmented scaffolds is still in a preliminary state, with a low scientific level of power (Kon et al. 2013). In application to chondrocytes, growth factors promote matrix synthesis, cell growth and migration, and facilitate protein transcription. The supra-physiological release of platelet-derived factors directly at the site of cartilage disease, particularly with interest to knee OA, may stimulate the natural regenerative signalling cascade and enhance the healing of tissue with further mediation of the anti-inflammatory response (Mascarenhas et al. 2014). In OA joints, PRP has been shown to affect local and infiltrating cells, mainly synovial cells, endothelial cells, those cells involved in innate immunity (such as macrophages) and cartilage and bone cellular components (Mifune et al. 2013; Dhillon et al. 2017). Additionally, PRP can affect inflammation and angiogenic processes, anabolism and catabolism balance in cartilage formation and alter the existing microenvironment during disease progression (Andia and Maffulli 2013).

The combined effects of PRP make it a potential option for management of knee OA, especially as a primary analgesic agent (Meheux et al. 2016). This is due to an increase in proliferation of tenocytes, osteoblasts, mesenchymal stem cells resulting in decreased pain levels post-operatively (Ogino et al. 2006). Despite promising preclinical results and wide clinical interest in orthopaedic and sports medicine, many unanswered questions regarding the clinical application and efficacy of PRP remain; not least in the production of PRP, which can cause wildly varying characteristics. A simple classification was first proposed in 2009 following the fibrin architecture and cell content (Pure PRP – Leukocyte-poor PRP, Leukocyte- and platelet rich plasma, Pure platelet-rich fibrin – Leukocyte-poor platelet-rich fibrin, Leukocyte- and platelet-rich fibrin). Each of these classifications had different growth factor release profiles (time, concentration) but studies found additional biological signatures and mechanisms within each family (Dohan Ehrenfest et al. 2014). A further classification can be included in the method of application (e.g. injections, glues) and the area of application (e.g. oral/maxillofacial surgery, skin wound healing). A more recent classification system called PAW (platelet, activation, white blood cells) based upon absolute number of platelets, activation method and presence or absence of white blood cells (DeLong et al. 2012). According to the authors, the specific determination of the components of the PRP is vital in allowing comparisons between studies. In 2016, a further classification was proposed. Magalon et al., (2016) suggested that the dose of injected platelets, the efficiency of the production (percentage of platelets recovered), the purity of the PRP (ratio of platelets, leucocytes and red blood cells) and the activation process; overall termed the DEPA (Dose, Efficiency, Purity, Activation) system. Whilst each of these systems has their merits, as a product for application in the clinic, they must be able to be characterised by the administrator or be detailed on the product, in which case, the effect of storage/transport should be disclosed in studies and discussed further in the literature.

Current Use of PRP in Musculoskeletal Tissues

PRP has been proposed as a promising biologic treatment with a wide range of applications in sports medicine (Lansdown and Fortier 2017). Injury type is significant, with benefits shown in the treatment of patella tendinopathy (Dragoo et al. 2014) and OA (Laudy et al. 2015) but not in Achilles tendinopathy or hamstring injuries (Manduca and Straub 2018). The available clinical studies on PRP as a treatment option suggest a good potential in favouring pain reduction and improved function for articular injuries to the ankle, knee and hip (Engebretsen et al. 2010). Overall, the evidence base for PRP across different injury types can be regarded as inconsistent and uncertain (McNamee et al. 2018). In a meta-analysis, Grassi et al., (2018) advocated PRP treatment as a safe procedure with negligible adverse effects which is readily available and has a minimal risk of reactivity compared to other exogenous compounds owing to the autologous nature of PRP injections. However, existing large and indiscriminate use of PRP injections for the treatment of acute muscle injuries in clinical practice is not justified by evidence. This caution should be applied to use in knee OA.

In muscle strain and tendon injuries, no statistical or clinically significant differences were found for RTP duration and re-injury rate, leading to the conclusion that PRP is no more effective than a placebo injection or intensive rehabilitation (de Vos et al. 2010, 2014; Creaney et al. 2011; de Jonge et al. 2011; Thanasas et al. 2011; Krogh et al. 2013; Hamilton et al. 2015; Reurink et al. 2015; Liddle and Rodríguez-Merchán 2015), however other studies have pointed to enhanced recovery (A Hamid et al. 2014; Chen et al. 2018). Between these reports, significant differences in the quality of the study are noted and should be used as a guide when analysing knee OA efficacy.

In knee OA, PRP injections aim to promote cartilage repair and relieve osteoarthritic symptoms, potentially delaying the need for joint replacement surgery. PRP injections have shown to influence the entire joint environment, leading to a short-term clinical improvement (Filardo et al. 2015) with PRP injections being considered a safe procedure with superior results compared with several alternative treatments (Laver et al. 2017). PRP is relatively easy to use due to its simple and rapid preparation and the minimally invasive administration requiring a simple intra-articular injection. Adverse effects are likely to be reduced due to the patient’s own proteins use and bioactive molecules can be appropriately concentrated, also eliminating potential drug interactions (Zhu et al. 2013). Without a synthetic element, PRP is, for the most part, not considered to be a drug or therapeutic substance and, does not therefore need to fulfil the regulatory requirements needed for other biologic therapies.

PRP use in Knee Osteoarthritis

The use of PRP in the treatment of degenerative knee OA has increased in recent years given its apparent high margin of safety and ease of production and administration (Smith 2016). Contrasting scientific evidence exist regarding PRP injections for knee OA, with the efficacy of PRP injections widely reported (Rahimzadeh et al. 2018). The effectiveness of PRP for pain treatment and knee joint function, its superiority compared with HA or placebo, and favourable outcomes in all stages of knee OA have all been reported (Kanchanatawan et al. 2016; Dai et al. 2017; Cole et al. 2017). In addition, the effects of PRP seemingly last longer and are superior in comparison with intramuscular injection therapies (Prieto-Alhambra et al. 2014). Comparisons between intra-articular injection of PRP versus placebo and HA therapy in mild and moderate knee OA have generally shown higher clinical outcome scores with PRP use (Filardo et al. 2012). Similarly, using Meta-analysis to compare the efficacy of PRP injections versus placebo or other therapeutic means for the treatment of knee OA (Bennell et al. 2017) have reported greater pain reduction (Laudy et al. 2015) and functional improvement (Chang et al. 2014) with the use of PRP but at the expense of an increase in nonspecific adverse events (Khoshbin et al. 2013).

PRP use has been advocated as a treatment option in all stages (early, middle and late stage) of knee OA. Intra-articular PRP injections in active patients with knee OA show significant improvements in pain reduction, improved symptoms and QoL (Gobbi et al. 2012). The release of growth factors from PRP occurs immediately with the prolonged and sustained release of growth factors from platelets possibly resulting in better biological healing and sustained clinical effects (Dhillon et al. 2017). Symptomatic relief for up to twelve months with increased benefits to patients with early knee degenerative changes has been found (Campbell et al. 2015) with significant improvements in function and reductions in pain with three injections per month yielding significantly better outcomes in the short-term (Huang et al. 2017). Improved pain outcomes after three months with greater effect in lower OA grades have been reported (Montañez-Heredia et al. 2016). In moderate knee OA, functional status and pain have improved with a minimum of two injections (Kavadar et al. 2015). In late stage knee OA, it may be that a single PRP intra-articular injection is effective for relieving pain and improving activities of daily living and QoL (Joshi Jubert et al. 2017).

Research into the efficacy of PRP has focused on comparing the effects of intra-articular PRP injections to other injection therapies. In many studies, PRP injections have improved functional outcomes when compared to HA and placebo controls and are appear more efficacious in reducing symptoms and improving and QoL (Raeissadat et al. 2015; Kanchanatawan et al. 2016). Kon et al., (2011) examined three homogenous groups of patients treated with three injections of PRP, low molecular weight HA, and high molecular weight HA and concluded that autologous PRP injections have longer efficacy than HA injections and enhance articular function. The results showed improved outcomes for the PRP group at six months with younger and more active patients achieving better results with a low degree of cartilage degeneration. Conversely, PRP causes a significantly greater acute inflammatory response, an increase in synoviocyte cell death (Braun et al. 2014) and induces more transient reactions than HA (Riboh et al. 2016). Spaková et al., (2012) compared three PRP injections with three HA injections in a randomised controlled trial (RCT) on one hundred and twenty patients and discovered better Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and Numerical Rating Scale (NRS) in the PRP group compared to the HA group (Table 3). In a separate RCT on one hundred and twenty patients, Cerza et al., (2012) compared four PRP injections at one-week intervals with low molecular weight HA and observed better improvement of WOMAC scores at twenty four weeks in the PRP group. No correlations with the grade of OA were found in either study. Additionally, better WOMAC scores were achieved at twenty four weeks using PRP by Sánchez et al., (2012) who examined one hundred and seventy six patients in a RCT with different grades of OA and compared three PRP injections at one-week intervals with HA. Similarly, better outcomes have been documented when comparing PRP to HA groups at six months (Li et al. 2011; Say et al. 2013). (Patel et al. 2013) compared normal saline with PRP and established the superiority of PRP over placebo as manifested by improved WOMAC scores at six months with patients experiencing benefits as early as eighteen days. In a follow-up study, Patel and Dhillon, (2014) hypothesised that the anti-inflammatory effect and chondral remodelling induced by PRP could be the reason for the improved clinical effects.

Limitations and Recommendations for Further Research

Despite the apparent positivity in the use of PRP  for treatment of knee OA, methodological concerns and considerable heterogeneity between studies are evident (Rodriguez-Merchan 2013b). Large RCTs are needed to further assess the efficacy and duration of PRP treatment for patients with knee OA (Rodriguez-Merchan 2013a; Lai et al. 2015). When planning or analysing treatments, frequency and number of injections, as well as the activation methods (in the case of anticoagulated PRP), storage aspects, time from plasma isolation and accompanying therapy should be considered as at present they vary widely between groups.  The greatest limiting factor for PRP use is the lack of standardisation with further research required to investigate how leukocyte inclusion, activation, and platelet concentration affect therapeutic efficacy (Chen et al. 2018). Potential classification systems are discussed in depth by Dohan Ehrenfest et al., 2014; Lana et al., 2017 and Alves and Grimalt, 2018. The cost-effectiveness of PRP, the demographic most likely to benefit and the optimal PRP protocol must all be researched further (Bennell et al. 2017). To this end, optimal timing, dose, volume, frequency, content and post injection rehabilitation techniques require clarification before this promising treatment can be widely implemented.

Compliance with Ethical Standards

The authors declare that they have no conflict of interest

Figure/Table Captions:

Figure 1: Comparison of a healthy (left) and OA knee joint (right)

Figure 2: PRP preparation process

Figure 3: Clinical applications of PRP

Table 1: Risk Factors for Knee OA.

Intrinsic  Extrinsic
Age: 

  • Advancing age effects of both sexes altered locomotor (sterognostic) control of opposing muscle groups.
Previous Trauma: 

  • Macrotrauma
  • Repetitive loading (e.g. Squatting) causing repetitive microtrauma
  • Increases risk 3.86 times
Sex: 

  • Females more prone to develop Heberden’s nodes
  • Being female increases risk 1.84 times
Co-morbidity 

  • Diseases such as:
  • cardiovascular disease
  • respiratory illness

can contribute/accelerate progression of knee OA

Heredity: 

  • Heberden’s nodes inherited as autosomal trait.
  • Genetically determined metabolic disorders (e.g. ochronosis and Ehler-Danlos syndrome) predispose to OA.
Body Mass: 

  • Overweight (BMI > 25)
  • Obesity (BMI > 30)
Ethnic origins: 

  • Increased incidence in European descent.
  • Less common in Asians.
  • Post-menopausal changes.
Resective Joint Surgery
Knee characteristics: 

  • Joint Laxity
  • Malalignment (femur-tibial angle -FTA)
Number of pregnancies (> 6)
Muscle Weakness

Table 2: Commonly Discussed Growth Factors and Effects associated with PRP.

Growth Factor Effect
Platelet-derived growth factor (PDGF) Angiogenesis; macrophage activation; 

proliferation and chemotaxis of fibroblasts:, collagen synthesis; enhanced proliferation of bone cells

Transforming growth factor-β (TGF-β) Fibroblasts proliferation; synthesis of type I collagen and fibronectin; deposition of bone matrix; inhibition of bone resorption
Platelet-derived epidermal growth factor (PDGR) Epidermal regeneration; promotes wound healing through stimulation of keratinocytes and dermal fibroblasts proliferation; enhanced production and effect of other growth factors
Vascular endothelial growth factor (VEGF) Vascularisation; stimulation of vascular endothelial cells
Insulin-like growth factor 1 (IGF-I) Fibroblasts chemotaxis; protein synthesis stimulation; enhanced bone formation
Platelet factor 4 (PF4) Enhanced influx of neutrophils; chemoattractant for fibroblasts
Epidermal growth factor (EGF) Cellular proliferation and differentiation
Hepatocyte growth factor (HGF) Inhibition of NF-κB transactivation activity; anti-inflammitory action through inhibition of monocyte-like chemotaxis
Stromal-cell derived growth factor-1α (SDF-1α) Supports primary adhesion and migration of progenitor cells

Table 3: Methods to assess impact of clinical intervention

Outcome Measure Function
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Assesses pain, stiffness, and physical function. Consists of 24 items divided into 3 subscales: 

  • Pain (5 items): during walking, using stairs, in bed, sitting or lying, and standing
  • Stiffness (2 items): after waking and later in the day
  • Physical Function (17 items): stair use, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on / taking off socks, rising from bed, lying in bed, getting in / out of bath, sitting, getting on / off toilet, heavy household duties, light household duties
Lequesne Assesses the effectiveness of therapeutic interventions. 

Sections for index:

  1.    Pain or discomfort
  1.    Maximum distance walked
  1.    Activities of daily living
EQ-VAS Patients’ own evaluation of overall health. 0 (worst possible health) to 100 (best possible health)
International Knee Documentation Committee (IKDC) Questionnaire Subjective overall function score. Questionnaire looks at 3 categories: 

  • symptoms
  •       sports activity
  •       knee function

Symptom subscale assists evaluation of pain, stiffness, swelling and giving-way of the knee.  Sports activity subscale focuses on functions such as ascending and descending stairs, rising from a chair, squatting and jumping.

References

 

A Hamid MS, Mohamed Ali MR, Yusof A, et al (2014) Platelet-rich plasma injections for the treatment of hamstring injuries. Am J Sports Med 42:2410–2418

Adatia A, Rainsford KD, Kean WF (2012) Osteoarthritis of the knee and hip. Part I: aetiology and pathogenesis as a basis for pharmacotherapy. J Pharm Pharmacol 64:617–625

Alves R, Grimalt R (2018) A review of platelet-rich plasma: history, biology, mechanism of action, and classification. Ski Appendage Disord 4:18–24

Andia I, Maffulli N (2013) Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol 9:721–730

Bennell KL, Hunter DJ, Paterson KL (2017) Platelet-rich plasma for the management of hip and knee osteoarthritis. Curr Rheumatol Rep 19:24

Blagojevic M, Jinks C, Jeffery A, Jordan KP (2010) Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthr Cartil 18:24–33

Braun HJ, Kim HJ, Chu CR, Dragoo JL (2014) The effect of platelet-rich plasma formulations and blood products on human synoviocytes. Am J Sports Med 42:1204–1210

Campbell KA, Saltzman BM, Mascarenhas R, et al (2015) Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee osteoarthritis? a systematic review of overlapping meta-analyses. Arthrosc J Arthrosc Relat Surg 31:2213–2221

Cerza F, Carnì S, Carcangiu A, et al (2012) Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med 40:2822–2827

Chang K-V, Hung C-Y, Aliwarga F, et al (2014) Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: a systematic review and meta-analysis. Arch Phys Med Rehabil 95:562–575

Chen X, Jones IA, Park C, Vangsness CT (2018) The efficacy of platelet-rich plasma on tendon and ligament healing: a systematic review and meta-analysis With Bias Assessment. Am J Sports Med 46:2020–2032

Cole BJ, Karas V, Hussey K, et al (2017) Hyaluronic acid versus platelet-rich plasma: a prospective, double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis. Am J Sports Med 45:339–346

Creaney L, Wallace A, Curtis M, Connell D (2011) Growth factor-based therapies provide additional benefit beyond physical therapy in resistant elbow tendinopathy: A prospective, single-blind, randomised trial of autologous blood injections versus platelet-rich plasma injections. Br J Sports Med 45:966–971

Cross M, Smith E, Hoy D, et al (2014) The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 73:1323–1330

Dai WL, Zhou AG, Zhang H, Zhang J (2017) Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Arthrosc – J Arthrosc Relat Surg 33:659–670.e1

de Jonge S, de Vos RJ, Weir A, et al (2011) One-year follow-up of platelet-rich plasma treatment in chronic achilles tendinopathy. Am J Sports Med 39:1623–1630

de Vos R-J, Windt J, Weir A (2014) Strong evidence against platelet-rich plasma injections for chronic lateral epicondylar tendinopathy: a systematic review. Br J Sports Med 48:952–956

de Vos RJ, Weir A, van Schie HTM, et al (2010) Platelet-rich plasma injection for chronic achilles tendinopathy. JAMA 303:144

DeLong JM, Russell RP, Mazzocca AD (2012) Platelet-rich plasma: the paw classification system. Arthrosc J Arthrosc Relat Surg 28:998–1009

Dhillon MS, Patel S, John R (2017) PRP in OA knee – update, current confusions and future options. Sicot-J 3:27

Dohan Ehrenfest DM, Andia I, Zumstein MA, et al (2014) Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles Ligaments Tendons J 4:3–9

Dragoo JL, Wasterlain AS, Braun HJ, Nead KT (2014) Platelet-rich plasma as a treatment for patellar tendinopathy. Am J Sports Med 42:610–618

Driban JB, McAlindon TE, Amin M, et al (2017) Risk factors can classify individuals who develop accelerated knee osteoarthritis: Data from the osteoarthritis initiative. J Orthop Res 36:876–880

Engebretsen L, Steffen K, Alsousou J, et al (2010) IOC consensus paper on the use of platelet-rich plasma in sports medicine. Br J Sports Med 44:1072–1081

Fernandes G, Yang S (2016) Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering. Bone Res 4:16036

Ficek K, Kamiński T, Wach E, et al (2011) Application of platelet rich plasma in sports medicine. J Hum Kinet 30:85–97

Filardo G, Di Matteo B, Di Martino A, et al (2015) Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation. Am J Sports Med 43:1575–1582

Filardo G, Kon E, Di Martino A, et al (2012) Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord 13:229

Gobbi A, Karnatzikos G, Mahajan V, Malchira S (2012) Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis. Sport Heal A Multidiscip Approach 4:162–172

Gouttebarge V, Inklaar H, Backx F, Kerkhoffs G (2015) Prevalence of osteoarthritis in former elite athletes: a systematic overview of the recent literature. Rheumatol Int 35:405–418

Grassi A, Napoli F, Romandini I, et al (2018) Is platelet-rich plasma (prp) effective in the treatment of acute muscle injuries? a systematic review and meta-analysis. Sport Med 48:971–989

Hamilton B, Tol JL, Almusa E, et al (2015) Platelet-rich plasma does not enhance return to play in hamstring injuries: a randomised controlled trial. Br J Sports Med 49:943–950

Heidari B (2011) Knee osteoarthritis prevalence, risk factors, pathogenesis and features: Part I. Casp J Intern Med 2:205–212

Huang P-H, Wang C-J, Chou W-Y, et al (2017) Short-term clinical results of intra-articular PRP injections for early osteoarthritis of the knee. Int J Surg 42:117–122

Jordan KP, Jöud A, Bergknut C, et al (2014) International comparisons of the consultation prevalence of musculoskeletal conditions using population-based healthcare data from England and Sweden. Ann Rheum Dis 73:212–218

Joshi Jubert N, Rodríguez L, Reverté-Vinaixa MM, Navarro A (2017) Platelet-rich plasma injections for advanced knee osteoarthritis: a prospective, randomized, double-blinded clinical trial. Orthop J Sport Med 5:232596711668938

Kabiri A, Hashemibeni B, Pourazar A, et al (2014) Platelet-rich plasma application in chondrogenesis. Adv Biomed Res 3:138

Kanchanatawan W, Arirachakaran A, Chaijenkij K, et al (2016) Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee. Knee Surgery, Sport Traumatol Arthrosc 24:1665–1677

Kavadar G, Demircioglu DT, Celik MY, Emre TY (2015) Effectiveness of platelet-rich plasma in the treatment of moderate knee osteoarthritis: a randomized prospective study. J Phys Ther Sci 27:3863–3867

Khoshbin A, Leroux T, Wasserstein D, et al (2013) The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systematic review with quantitative synthesis. Arthrosc J Arthrosc Relat Surg 29:2037–2048

Kon E, Filardo G, Di Martino A, Marcacci M (2011) Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use. Knee Surgery, Sport Traumatol Arthrosc 19:516–527

Kon E, Filardo G, Di Matteo B, et al (2013) PRP-augmented scaffolds for cartilage regeneration: a systematic review. Oper Tech Sports Med 21:108–115

Krogh TP, Fredberg U, Stengaard-Pedersen K, et al (2013) Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline. Am J Sports Med 41:625–635

Lai LP, Stitik TP, Foye PM, et al (2015) Use of platelet-rich plasma in intra-articular knee injections for osteoarthritis: a systematic review. PM&R 7:637–648

Lana JFSD, Purita J, Paulus C, et al (2017) Contributions for classification of platelet rich plasma – proposal of a new classification: MARSPILL. Regen Med 12:565–574

Lansdown DA, Fortier LA (2017) Platelet-rich plasma: formulations, preparations, constituents, and their effects. Oper Tech Sports Med 25:7–12

Laudy ABM, Bakker EWP, Rekers M, Moen MH (2015) Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med 49:657–672

Laver L, Marom N, Dnyanesh L, et al (2017) PRP for degenerative cartilage disease: a systematic review of clinical studies. Cartilage 8:341–364

Li M, Zhang C, Ai Z, et al (2011) [Therapeutic effectiveness of intra-knee-articular injection of platelet-rich plasma on knee articular cartilage degeneration]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 25:1192–6

Liddle AD, Rodríguez-Merchán EC (2015) Platelet-rich plasma in the treatment of patellar tendinopathy. Am J Sports Med 43:2583–2590

Lotz MK, Caramés B (2011) Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA. Nat Rev Rheumatol 7:579–587

Lubkowska A, Dolegowska B, Banfi G (2012) Growth factor content in PRP and their applicability in medicine. J Biol Regul Homeost Agents 26:3–22

Magalon J, Chateau AL, Bertrand B, et al (2016) DEPA classification: a proposal for standardising PRP use and a retrospective application of available devices. BMJ Open Sport Exerc Med 2:e000060

Manduca ML, Straub SJ (2018) Effectiveness of prp injection in reducing recovery time of acute hamstring injury: A Critically Appraised Topic. J Sport Rehabil 27:480–484

Marx RE (2001) Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent 10:225–8

Mascarenhas R, Saltzman B, Fortier L, Cole B (2014) Role of platelet-rich plasma in articular cartilage injury and disease. J Knee Surg 28:003-010

Mather RC, Koenig L, Kocher MS, et al (2013) Societal and economic impact of anterior cruciate ligament tears. J Bone Jt Surgery-American Vol 95:1751–1759

McNamee MJ, Coveney CM, Faulkner A, Gabe J (2018) Ethics, evidence based sports medicine, and the use of platelet rich plasma in the english premier league. Heal Care Anal 26:344–361

Meheux CJ, McCulloch PC, Lintner DM, et al (2016) Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthrosc J Arthrosc Relat Surg 32:495–505

Michael JW-P, Schlüter-Brust KU, Eysel P (2010) The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. Dtsch Aerzteblatt Online 107:152–162.

Mifune Y, Matsumoto T, Takayama K, et al (2013) The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair. Osteoarthr Cartil 21:175–185

Montañez-Heredia E, Irízar S, Huertas P, et al (2016) 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. Int J Mol Sci 17:1064

Murphy L, Helmick CG (2012) The impact of osteoarthritis in the united states. Orthop Nurs 31:85–91

Neogi T, Zhang Y (2013) Epidemiology of osteoarthritis. Rheum Dis Clin North Am 39:1–19

Ng NTM, Heesch KC, Brown WJ (2012) Strategies for managing osteoarthritis. Int J Behav Med 19:298–307

Ogino Y, Ayukawa Y, Kukita T, Koyano K (2006) The contribution of platelet-derived growth factor, transforming growth factor-β1, and insulin-like growth factor-I in platelet-rich plasma to the proliferation of osteoblast-like cells. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology 101:724–729

Parrish WR, Roides B (2018) Platelet rich plasma in osteoarthritis: More than a growth factor therapy. Musculoskelet Regen 3:e1518

Patel S, Dhillon MS (2014) The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis: letter to the editor. Am J Sports Med 42:NP30-NP31

Patel S, Dhillon MS, Aggarwal S, et al (2013) Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis. Am J Sports Med 41:356–364

Pavlovic V, Ciric M, Jovanovic V, Stojanovic P (2016) Platelet rich plasma: A short overview of certain bioactive components. Open Med 11:242–247

Pereira D, Peleteiro B, Araújo J, et al (2011) The effect of osteoarthritis definition on prevalence and incidence estimates: a systematic review. Osteoarthr Cartil 19:1270–1285

Prieto-Alhambra D, Judge A, Javaid MK, et al (2014) Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Ann Rheum Dis 73:1659–1664

Raeissadat SA, Rayegani SM, Hassanabadi H, et al (2015) Knee osteoarthritis injection choices: platelet- rich plasma (prp) versus hyaluronic acid (a one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord 8:CMAMD.S17894

Rahimzadeh P, Imani F, Faiz SHR, et al (2018) The effects of injecting intra-articular platelet-rich plasma or prolotherapy on pain score and function in knee osteoarthritis. Clin Interv Aging Volume 13:73–79

Reurink G, Goudswaard GJ, Moen MH, et al (2015) Rationale, secondary outcome scores and 1-year follow-up of a randomised trial of platelet-rich plasma injections in acute hamstring muscle injury: the Dutch Hamstring Injection Therapy study. Br J Sports Med 49:1206–1212

Riboh JC, Saltzman BM, Yanke AB, et al (2016) Effect of leukocyte concentration on the efficacy of platelet-rich plasma in the treatment of knee osteoarthritis. Am J Sports Med 44:792–800

Rodriguez-Merchan EC (2013a) Intra-articular injections of hyaluronic acid and other drugs in the knee joint. HSS J ® 9:180–182

Rodriguez-Merchan EC (2013b) Intraarticular injections of platelet-rich plasma (prp) in the management of knee osteoarthritis. Arch bone Jt Surg 1:5–8

Sánchez M, Fiz N, Azofra J, et al (2012) A randomized clinical trial evaluating plasma rich in growth factors (prgf-endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthrosc J Arthrosc Relat Surg 28:1070–1078

Say F, Gürler D, Yener K, et al (2013) Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis. Acta Chir Orthop Traumatol Cech 80:278–83

Silverwood V, Blagojevic-Bucknall M, Jinks C, et al (2015) Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthr Cartil 23:507–515

Smith PA (2016) Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee osteoarthritis. Am J Sports Med 44:884–891

Spaková T, Rosocha J, Lacko M, et al (2012) Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil 91:411–417

Sundman EA, Cole BJ, Karas V, et al (2014) The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med 42:35–41

Thanasas C, Papadimitriou G, Charalambidis C, et al (2011) Platelet-rich plasma versus autologous whole blood for the treatment of chronic lateral elbow epicondylitis. Am J Sports Med 39:2130–2134

van Buul GM, Koevoet WLM, Kops N, et al (2011) Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. Am J Sports Med 39:2362–2370

Wruck CJ, Fragoulis A, Gurzynski A, et al (2011) Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice. Ann Rheum Dis 70:844–850

Xing D, Wang B, Zhang W, et al (2017) Intra-articular platelet-rich plasma injections for knee osteoarthritis: An overview of systematic reviews and risk of bias considerations. Int J Rheum Dis 20:1612–1630

Yu D, Peat G, Bedson J, Jordan KP (2015) Annual consultation incidence of osteoarthritis estimated from population-based health care data in England. Rheumatology 54:2051–2060

Zhang W, Moskowitz RW, Nuki G, et al (2008) OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil 16:137–162

Zhu Y, Yuan M, Meng HY, et al (2013) Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review. Osteoarthr Cartil 21:1627–1637



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