Complete the 2 tables using the article attached. See the example for guidance .

Originalien

Orthopäde 2019 · 48:239–247 https://doi.org/10.1007/s00132-018-03659-5 Published online: 8 January 2019 © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Yong Huang1 · Xiaolu Liu1 · Xinliang Xu2 · Junbin Liu2

1 School of Medicine and Life Sciences, Jinan University, Jinan, China 2 Department of Traumatology, Jining NO.1 People’s Hospital of Shandong, Jining, China

Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis A prospective randomized controlled study

Introduction

Osteoarthritis of the knee (KOA) is a common condition associated with pain and morbidity [1]. The increasing number of patients with symptomatic KOA will continue to place an increas- ingly larger economic burden on global healthcare systems [1]. The third Na- tional Health and Nutrition Survey of the USA showed that the prevalence of symptomatic KOA was 12.1%, similar to that in Europe [2]. According to the lat- est Chinese epidemiological survey data, the prevalence of symptomatic KOA in China was 8.1%. This means that China currently has approximately 110 million KOA patients [3]. The prevalence of KOA increases gradually with age. The incidence of patients under 50 years of age is 5.2%, while it has reached 11% among those over 60 years old (. Fig. 1 [4]).

Knee arthroplasty is a reliable and successful surgical treatment to address end-stage KOA. Unfortunately, the cost of and time delay to knee replacement is potentially prohibitive in some coun- tries. In the USA potential overutiliza- tion of arthroplasty is being met with increasing scrutiny with respect to pre- operativenonsurgicaltreatment[5]. This includes both nonpharmacological and pharmacological approaches. Intra-ar- ticular (IA) corticosteroid and viscosup- plementation injections have successful, albeit short-term benefits according to

several meta-analyses [6, 7], randomized controlled trials [8, 9] and large retro- spective studies [10, 11]. Injections of hyaluronic acid (HA) were found to cure mild to moderate OA in patients while platelet-rich plasma (PRP) knee injec- tionsalsoexistinclinicaltrials. Clinically, thecomparativeefficacyandeffectiveness of IA injections of PRP, HA, and CS in the treatment of KOA are unclear and controversial. Moreover, no study has directly and concurrently compared IA- HA, IA-CS and IA-PRP in early KOA. A prospective, randomized, controlled trial was therefore performed to primar- ily compare the efficacy of pain reduction with IA-HA, IA-CS and IA-PRP in KOA. It was hypothesized that IA-PRP would betheoptimalIAadministrationmethod for the treatment of KOA.

Material and methods

This study was approved by the Ethics Committee of the Jining NO.1 People’s Hospital of Shandong.

Patients

Thiswasaprospective, randomizedstudy initiated in May 2016. Out of 265 pa- tients, 120 that met the inclusion criteria received IA-HA, IA-CS and IA-PRP in- jections into the knee for early stages of OA (Kellgren–Lawrence grade 1–2) [12].

Inclusion criteria

Patients with symptomatic KOA (Kell- gren-Lawrence grade 1–2 on radio- graphs) between the ages of 40 and 65 years, having a body mass index (BMI)< 30, with stable knees without

Abbreviations BMI Body mass index

CS Corticosteroids

DVT Deep venous thrombosis

EQ-VAS EuroQol-VAS

HA Hyaluronic acid

HIV Human immunodeficiencyvirus

IA Intra-articular

IGF-1 Insulin-like growth factor 1

IKDC International Knee Documenta- tion Committee

KOA Knee osteoarthritis

KOOS Knee injury and osteoarthritis outcome score

MRI Magnetic resonance imaging

PRP Platelet-richplasma

RCF Relative centrifugal force

TGF-beta Transforming growth factor beta

VAS Visual analog scale

VEGF Vascular endothelial growth factor

WOMAC Western Ontario and McMasters Universities

Der Orthopäde 3 · 2019 239

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5.20%

7.60%

11.00%

9.10%

0 %

2 %

4 %

6 %

8 %

10 %

12 %

<50 50–59 60–69 ≥70 Age (years)

Fig. 1 9 The preva- lence of knee os- teoarthritis in dif- ferent age groups in China

malalignment or maltracking of the patella were included in the study. Ad- ditional inclusion criteria were patients having pain with no relief using anti-in- flammatory agents even after 3 months, normal blood results and coagulation profile (platelets 150,000–450,000/l), patients who had not undergone any surgery on the affected knee within 2 years prior to the first injection and zero, traces or 1+ effusion on the grading scale based on the Stroke test [13].

Exclusion criteria

Patients diagnosed with tricompartmen- tal OA, rheumatoid arthritis or concomi- tant hip OA were not included in the study. A previous high tibial osteotomy or cartilage transplantation procedure, grades2+and3+effusioninthekneejoint (requiringaspiration)basedontheStroke test, blood diseases, systemic metabolic disorders, immunodeficiency, hepatitisB or C, HIV positive status, local or sys- temic infection, ingestion of anti-platelet medication within 7 days prior to the in- jection and treatment with IA or oral corticosteroids in the 3 months prior to the first injection were considered crite- ria for exclusion in addition to patients who refused to participate.

PRP preparation

Samples of 8ml blood were obtained from the cubital vein and centrifuged for 5min at 1500 g centrifugal force (RCF) or 3500 pm as per the recommendations of the manufacturer. This system did not use a second centrifugation process. Centrifugation of whole venous blood takes advantage of differing density gradients of the components in blood to concentrate platelets. Erythrocytes, which are most dense, remain as the packed cell layer at the bottom of the centrifuge container. The buffy coat of white blood cells is above this while the platelets are at the highest concentration intheplasmajustabovethebuffycoatand decrease in concentration towards the top of the plasma layer. After centrifuga- tion, plateletrecoverywas >80% (twofold increase) and total leucocyte concentra- tion was below the normal level-specific granulocyte depletion >95% in 4ml of PRP. Leucocyte poor-PRP (LP-PRP) was obtained according to Dohan Ehrenfest et al. classification [14] which was P2 Bb as per the PAW classification [15]. The PRP was aspirated into a syringe and a topical anesthetic skin refrigerant was applied locally before IA infiltration by a suprapatellar approach using sterile aseptic precautions. The PRP was ac- tivated in vivo when the platelets were exposed to collagen or von Willebrand

factor, leading to aggregation. After treatment, patients were allowed weight bearing and local ice application was recommended for 20min every 2–3h for 24h. Vigorous activities of the knee were not recommended for 48h.

HA and CS preparation

The IA injection of HA (sodium hyaluro- nate, molecular weight 500– 730kDa) was provided by the biochemical indus- try corporation (SK chemical research co., LTD, Tokyo, Japan) and 2ml was injected into the knee of the patients each week for 3 weeks; IA injection of 1ml CS produced by Shanghai Scher- ing-Plough pharmaceutical company (Shanghai, China) was similarly injected into the knee. The injection method was same as for the IA-PRP group and after treatment patients were allowed weight bearing and local ice application was recommended for 20min every 2–3h for 24h. Vigorous activities of the knee were not recommended for 48h. All operations in the same laminar flow room were administered by the same group of persons for IA injection.

Outcome measures

Outcome following treatment was as- sessed using the Western Ontario and McMaster Universities (WOMAC) and visual analogue scales (VAS, 0= no pain up to 10= worst possible pain) [15] scor- ingsystemswhichwererecordedthrough questionnaires completed by the patients prior to the first injection and then at 3, 6, 9 and 12 months follow-up. Data were recorded in SOCRATESTM (2012, Or- tholink PTY Ltd., Balmain, New South Wales, Australia) orthopedic outcomes software. Any adverse events occurring within 12 months postoperatively were recorded at the time of follow-up.

Statistical analysis

Distributions of demographic data, base- line data, and outcomes were assessed using measures of central tendency (mean, standard deviation) for quanti- tative variables and with percentages for qualitative variables. The general linear

240 Der Orthopäde 3 · 2019

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Abstract · Zusammenfassung

Orthopäde 2019 · 48:239–247 https://doi.org/10.1007/s00132-018-03659-5 © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Y. Huang · X. Liu · X. Xu · J. Liu

Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis. A prospective randomized controlled study

Abstract Background. Knee osteoarthritis (KOA) is a degenerative joint disease leading to pain and disability for which no curative treatment exists. Intra-articular (IA) therapies are part of this multimodal approach and are approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA). Platelet-rich plasma (PRP), hyaluronic acid (HA), and corticosteroids (CS) have been increasingly used in recent years to treat KOA. Purpose. To determine whether IA-PRP was superior to IA-HA or IA-CS administration routes in these patients. Material and methods. In this trial the pa- tients were randomized to IA-HA (2ml/week, for 3 weeks), IA-CS (1ml) or IA-PRP (3 times, 4ml, every 3 weeks) groups. The outcome

was assessed using the Western Ontario and McMaster Universities (WOMAC) score prior to the first injection and then at 3, 6, 9 and 12 months. Pain was evaluated by a visual analogue scale (VAS) prior to treatment and after 12 months. Results. In this study 120 patients were randomized into 3 groups. There was a significant improvement in all scores (WOMAC, VAS) in each group compared to the pretreatment values (P< 0.05). The mean WOMAC scores for the IA-HA group from pretreatment to 3, 6, 9, and 12 months were 47.23± 5.37, 25.02± 4.98, 26.38± 5.20, 27.86± 4.34, and 30.64± 8.36, respectively. Similar improvements were noted in the IA-CS and IA-PRP groups. There were no significant

differences in the WOMAC scores between the 3 groups 3 months after treatment (P> 0.05) but IA-PRP showed significantly lower scores 6, 9 and 12 months after treatment (P< 0.05). Conclusion. Intra-articular PRP injections into the knee for symptomatic early stages of KOA are a valid treatment option. The clinicalefficacy of IA-PRP is comparableto that of the IA-HA and IA-CS forms after 3 months and the long-term efficacy of IA PRP is superior to IA-HA and IA-CS.

Keywords Degenerative joint disease · Visual analog scale · Multimodal treatment · Assessment, outcomes · Viscosupplementation

Intraartikuläre Injektionen mit plättchenreichem Plasma, Hyaluronsäure oder Kortikosteroiden bei Kniearthrose. Eine prospektive, randomisierte, kontrollierte Studie

Zusammenfassung Hintergrund. Kniearthrose ist eine de- generative Gelenkerkrankung, die mit Schmerzen und Einschränkungen einhergeht, für die es keine kurative Behandlung gibt. Intraartikuläre (IA) Therapien sind Teil dieses multimodalen Therapieansatzes und wurden von der Food and Drug Administration (FDA) und der Europäischen Arzneimittel-Agentur (EMA) zugelassen. Plättchenreiches Plasma (PRP), Hyaluronsäure (HA) und Kortikosteroide (CS) wurden in den letzten Jahren zunehmend zur Behandlung der Kniearthrose verwendet. Zweck. Es sollte festgestellt werden, ob bei diesen PatientenIA-PRP einer Behandlung mit IA-HA oder IA-CS überlegen ist. Material und Methoden. In dieser Studie wurden die Patienten in eine IA-HA-Gruppe (2ml/Woche für 3 Wochen), eine IA-CS- Gruppe (1ml) oder eine IA-PRP-Gruppe (3- mal 4ml alle 3 Wochen) randomisiert. Die

Ergebnisse wurden vor der ersten Injektion und dann nach 3, 6, 9 und 12 Monaten mittels des Western Ontario and McMaster Universities (WOMAC) Score ausgewertet. Die Schmerzen wurden vor der Behandlung und 12 Monate danach mittels der visuellen Analogskala (VAS) bewertet. Ergebnisse. In dieser Studie wurden 120 Pateinten in 3 Gruppen randomisiert. In allen Scores (WOMAC, VAS) zeigte sich eine signifikante Verbesserung in jeder Gruppe im Vergleich zu den Werten vor der Behandlung (p< 0,05). Die mittleren WOMAC-Scores der IA-HA-Gruppe vom Zeitpunkt vor der Behandlung bis zu 3, 6, 9 und 12 Monaten be- trugen 47,23± 5,37, 25,02± 4,98, 26,38± 5,20, 27,86± 4,34 bzw. 30,64± 8,36. Ähnliche Verbesserungen wurden in der IA-CS- und IA-PRP-Gruppe festgestellt. Es gab keine signifikanten Unterschiede in den WOMAC-

Scores zwischen den 3 Gruppen 3 Monate nach der Behandlung (p> 0,05), aber IA-PRP zeigte signifikant niedrigere Scores 6, 9 und 12 Monate nach der Therapie (p< 0,05). Schlussfolgerung. Intraartikuläre PRP-Injek- tionen ins Kniegelenk im symptomatischen Frühstadium einer Kniearthrose stellen eine valide Behandlungsoption dar. Die klinische Wirksamkeit von IA-PRP ist vergleichbar mit der Wirksamkeit der IA-HA- und IA- CS-Therapie nach 3 Monaten. Bezüglich der Langzeit-Wirksamkeit ist IA-PRP der Behandlung mit IA-HA und IA-CS überlegen.

Schlüsselwörter Degenerative Erkrankung · Visuelle Analog- skala · Multimodale Therapie · Bewertung, Ergebnisse · Viskosupplementation

model for repeated measurement tests was performed to investigate within time variations for the continuous variables (WOMAC, VAS) for all patients and each evaluated subgroup. Categorical variables were compared using the χ2 and Fisher’s exact tests. All data analyses were performed using SPSS for Win-

dows, Version 19.0 (SPSS Inc., Chicago, IL, USA). Significance was set at P< 0.05.

Results

Patient demographics

During the recruitmentperiod from May 2016 to October 2017 a total of 265 pa-

tients were scheduled to receive IA injec- tions into the knee and were systemati- cally followed up from the start of treat- ment. Among these patients, 84 were ineligible, while 61 were excluded from participation. Hence, the trial was com- pleted with 120 patients. No patients were lost or excluded during the follow- up (. Fig. 2).

242 Der Orthopäde 3 · 2019

Assessed for eligibility (N=265)

IA-HA group (N=40)

Injected 2ml HA

Lost to follow-up (N=0)

Analyzed (N=40) Excluded from analysis (N=0)

IA-CS group (N=40)

Injected 1ml CS

Lost to follow-up (N=0)

Analyzed (N=40) Excluded from analysis (N=0)

IA-PRP group (N=40)

Injected 4ml PRP

Lost to follow-up (N=0)

Analyzed (N=40) Excluded from analysis (N=0)

Rejected to participate (N=61)

Not eligible for inclusion (N=84)

Kellgren-Lawrence grade ≥III (N=47)

Rheumatoid arthritis (N=5)

Blood diseases (N=1)

Hepatitis B (N=2)

Under antiplatelet medication (N=3)

Intra-articular treatment (N=17)

Enrollment

Follow-up

Analysis

Randomization (N=120)Allocation

Effusion grade ≥2+ (N=9)

Fig. 2 9 Flow diagram of patients eligible for this study. CS Chondroitin sulphate, HA Hyaluronic acid; IA-HA intra-articular hyaluronic acid, IA-CS in- tra-articularcorticos- teroids, IA-PRP intra-artic- ularplatelet-rich plasma, PRPPlatelet-rich plasma

The mean patient age (and standard deviation) was 54.5± 1.2 years, 65 pa- tients (54%) were men and 55 (46%) were women. The mean patient BMI was 24.75± 3.62kg/m2. Baseline char- acteristics were comparable among the allocation groups (. Table 1).

WOMAC scores

There was a significant improvement in WOMAC scores at each follow-up compared to the pretreatment value (P< 0.05). When comparing the effect of treatment between the 3 groups after 3 months they showed similar and signif- icant improvement (P> 0.05); however,

the results at 6, 9, and 12 months in the IA-PRP group showed a significant dif- ference to the IA-HA and IA-CS groups and with a greater improvement in re- sults in the patients (P< 0.05) (. Table 2; . Fig. 3).

VAS pain scores

The VAS scores decreased from 4.52at baseline assessment to 2.14at 12-month follow-up for the IA-HA group. For the IA-CS group they decreased from 4.64 to 2.26 and in IA PRP group the VAS scores decreased from 4.57 to 1.98. The benefit in pain reduction as measured by the VAS was significant (P< 0.05) in

the IA-HA, IA-CS and IA-PRP groups compared to pretreatment (. Table 3).

From pretreatment to the final fol- low-up, none of patients sustained low- grade fever, a deep venous thrombosis (DVT) or an infection (. Table 4). Mild complications such as pain, nausea, and dizziness, which were of short duration, were observed in 2 patients (1.7%) in the IA-HA group, 3 patients (2.5%) in the IA-CS group, and 5 patients (4.2%) in the IA-PRP group (. Table 4). These conditions were generally relieved after 24 or 48h.

Der Orthopäde 3 · 2019 243

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Table 1 Baseline characteristicsandperioperativedemographicsof the patients

Variable IA-HA group (n= 40)

IA-CS group (n= 40)

IA-PRP group (n= 40)

P-value

Demographic characteristics

Age (years) 54.8± 1.1 54.3± 1.4 54.5± 1.2 0.13a

Male (n, %) 19 (15.8%) 21 (17.5%) 25 (20.8%) 0.85b

Height (m) 1.65± 0.07 1.64± 0.08 1.66± 0.05 0.12a

Weight (kg) 62.54± 9.10 63.85± 9.37 62.41± 8.53 0.73a

BMI (kg/m2) 24.51± 3.09 24.56± 3.62 25.23± 4.15 0.37a

Injection side (n, %) 0.55b

Right 21 (17.5%) 24 (20.0%) 18 (15.0%) –

Left 19 (15.8%) 16 (13.3%) 22 (18.3%) –

Comorbidities (n, %)

Hypertension 6 (5.0%) 5 (4.2%) 3 (2.5%) 0.58b

Diabetes mellitus 2 (1.7%) 1 (0.8%) 2 (1.7%) 0.81b

BMI body mass index, IA intra-articular, HA hyaluronic acid, CS corticosteroids, PRP platelet-rich plasma aThe P-value represents the result of one-way analysis of variance for independent means for continuous variables bThe P-value represents the result of the χ2-test or Fisher’s exact tests for categorical variables among the 3 groups

Table 2 WOMAC scores during the follow-up

Variable Preinjection 3 months 6 months 9 months 12 months

IA-HA group (n= 40)

47.23± 5.37 25.02± 4.98a 26.38± 5.20b 27.86± 4.34bc 30.64± 8.36bc

IA-CS group (n= 40)

46.58± 5.74 24.78± 4.55a 25.00± 4.65b 28.16± 5.12bc 32.18± 6.88bc

IA-PRP group (n= 40)

48.19± 4.96 25.15± 5.24a 21.14± 5.17b 20.12± 4.66bc 16.10± 7.22bc

P-value >0.05 >0.05 <0.01 <0.01 <0.01

IA intra-articular, HA hyaluronic acid, CS corticosteroids, PRP platelet-rich plasma 3 months after treatment compared with pre-treatment aP< 0.05; 6, 9, 12 months after treatment compared with 3 months after treatment bP> 0.05; Compared with 6, 9, 12 months after treatment between the three groups cP< 0.05

Discussion

It was determined that IA-PRP injections significantly improved the clinical out- comes in symptomatic KOA. The use of PRP was also shown to be significantly better than HA or CS for the treatment of symptomatic KOA at the time of fol- low-up. Treating OA nonoperatively has been ongoing for several decades. Multi- ple studies have reported the use of HA, PRP, and corticosteroids, among other agents, in the nonoperative treatment of OA. While there are a number of studies documenting the use of HA or CS in the treatment of OA, there are limited stud- ies documenting the use of PRP for the same purpose. More importantly, there

are very limited studies comparing the use of PRP with that of HA or CS in the treatment of KOA. To address these concerns, this prospective, randomized, controlled study was conducted to com- pare the similarities and difference be- tween the three groups.

Current treatments focus on pain reduction, exercise therapy and in end- stage OA joint replacement. No cura- tive treatment exists for OA. Since joint arthroplasties have a limited lifespan, there is a great need for disease-modify- ing drugs or therapies in the early stages. Therefore, a biological therapy for tissue injury that has emerged in recent years is treatment with PRP, which is a plasma product extracted from whole blood that

contains at least 1.0× 106 platelets per μl [16]. The platelets undergo degranu- lation, after which they release growth factors and cytokines such as trans- forming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF) [16–18], insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor and vascular endothelial growth factor (VEGF). Both PDGF and TGF-beta are two important factors in tissue healing. From preclinical research it is known that PRP promotes the proliferation of cells derived from human synovium and cartilage [19, 20] and that PRP- treated chondrocytes repair cartilage better than nontreated chondrocytes [21]. These cells in turn produce more superficial zone protein, which functions as a boundary lubricant that helps to re- duce friction and wear [20, 22, 23]. The PRP itself was also shown to reduce fric- tion in bovine articular cartilage explants [20]. The anti-inflammatory effects of PRP have been demonstrated both in a co-culture system of osteoarthritic cartilage and synovium [20] and in hu- man osteoarthritic chondrocytes, where it reduced multiple proinflammatory effects induced by interleukin 1b [24]. Furthermore, in a canine OA model, multiple PRP injections were shown to have beneficial effects on pain and func- tional impairment but no effect on the severity of radiographic OA [25]. More- over, several clinical trials in OA have concluded that IA-PRP injections are safe and have a beneficial effect on OA symptoms, such as pain and swelling for up to 12 months [26–30]. Patel et al. [31] compared the outcome fol- lowing single and double PRP injections compared to a control group for early OA at 6 weeks, 3 and 6 months. They concluded that there was a significant improvement in WOMAC scores at all follow-ups when PRP was administered, with no difference between single and double injections. Hart et al. [32] in a prospective study of 50 patients admin- istered 9 injections in 1 year to assess if PRP can increase tibiofemoral cartilage regeneration in the knee. They reported improvement in all scores at 12 months but with no significant cartilage regener- ation. Torrero et al. [33] in a prospective

244 Der Orthopäde 3 · 2019

48.19

25.15

21.14 20.12

16.1

46.58

24.78 25 28.16

32.18

47.23

25.02 26.38

27.86

30.64

15

20

25

30

35

40

45

50

Pretreatment 3 months 6 months 9 months 12 months

PRP CS HA

M ea

n W

O M

A C

s co

re

Fig. 3 8 VariationinmeanWOMACscoreoverthecourseofthestudyateachfollow-up. PRPplatelet-rich plasma,CS corticosteroids,HA hyaluronic acid

Table 3 Details of visual analog scale (VAS)scores forpainpretreatment andafter12months

Variable IA-HA group (n= 40)

IA-CS group (n= 40)

IA-PRP group (n= 40)

VAS scores

At preinjection 4.54± 0.596 4.64± 0.543 4.57± 0.610

At 12-month follow-up 2.14± 1.523 2.26± 1.707 1.98± 1.437

Difference

(preinjection vs. 2.400± 1.549 2.380± 1.629 2.590± 1.580

6-month follow-up) – – –

P-value 0.001 0.001 0.001

IA intra-articular, HA hyaluronic acid, CS corticosteroids, PRP platelet-rich plasma

Table 4 Outcomes of adverse events in thethree groups

Variable IA-HA group (n= 40)

IA-CS group (n= 40)

IA-PRP group (n= 40)

P-value

Adverse events

DVT 0 0 0 NA

Low-grade fever 0 0 0 NA

Infections 0 0 0 NA

Pain 2 (1.7%) 3 (2.5%) 5 (4.2%) 0.46a

NA not applicable, DVT deep venous thrombosis, IA intra-articular, HA hyaluronic acid, CS corticos- teroids, PRP platelet-rich plasma aP-value represents the result of the χ2-test or Fisher’s exact test for categorical variables among the 3 groups

study included patients aged 18–65 years and reported significant improvement in the KOOS and VAS score after a sin- gle injection up to 6 months after the treatment. Filardo et al. [34] compared a single spin and double spin method of preparation of PRP in 144 patients, demonstrating a significant clinical im- provement in both groups with better

results in younger patients. Similarly, in a comparative study to assess the effi- cacy of PRP and hyaluronic acid in 150 patients over 6 months, Kon et al. [35] showed improved IKDC and VAS scores in both groups after 2 and 6 months with better results in the PRP group.

To the best of our knowledge, this is the first study to compare the clinical im-

provement between IA-HA, IA-CS, and IA-PRP in KOA. There are very few ran- domized control trials (RCT) compar- ing IA injections of PRP, HA, and CS. From February 2015, 5 supplementary RCT were published: 4 RCT comparing IA-PRP to IA-HA [29, 34, 36, 37] and 1 RCT comparing IA-PRP to IA-CS [38]. The most important finding of this study was that IA-PRP was superior to IA-HA and IA-CS in reducing pain and recov- ering physical function in the long term for KOA.

Although this study was carefully de- signed, several limitations exist. First, this studyonlyincluded patients between the ages of 40 and 65 years, who are non- professional athletes inordertoeliminate bias which could occur due to extremes of age. In some previous studies the age group has been as wide as 18–81 years [33, 39]. Second, thisstudyonlyrecorded the WOMAC scores prior to the first in- jection and then at the end of 12- month follow-up. We can’t find the results of 18 months or 2 years. In a prospective study including 91 patients, a follow-up of 24 months was reported [40, 41]; pa- tients received three IA-PRP injections at monthly intervals, and all parameters worsened at 2 years with significantly lower levels of IKDC objective, subjec- tive and EQ-VAS scores with respect to the 12-month evaluation (IKDC objec- tive fell from 67% to 59% of normal and nearly normal knees; IKDC subjective score was reduced from 60% to 51%, al- though they remained higher than the basal level). Jang et al. [42] showed de- terioration in scores within the 1st year. Finally, in this study the outcomes be- tween the three groups with WOMAC and VAS scores were compared but did not have post-treatment MRI results for every patient; therefore, the changes in the knee cartilage atthe end of12 months cannot be seen.

The optimal IA administration for KOA has remained unclear and contro- versial. Corticosteroids IA injections are a part of the pharmacological treatment of the acute phase or flare of KOA and IA-HA injections are part of the pharma- cological treatment of the chronic phase of KOA. Although multiple studies have reported the safety of using of PRP in the

Der Orthopäde 3 · 2019 245

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early stages of osteoarthritis of the knee [26–35, 38], high-quality randomized control trials are needed to determine the safety and improvements of IA-PRP.

Conclusion

TheuseofIA-PRPinjectionsintotheknee for symptomatic early stages of KOA are a valid treatment option. There is a sig- nificant reduction in pain and clinical improvement after 3 months, which can be further improved at 12 months. Al- though the optimal method of IA treat- ment remains a matter of debate in the literature, the results of the experiment show an encouraging improvement in all scores compared to the pretreament val- ues.

Corresponding address

Junbin Liu Department of Traumatology, Jining NO.1 People’s Hospital of Shandong No.6, Jiankang Road, 272011 Jining, Shandong, China [email protected]

Acknowledgements. The authors would like to thank the research assistants from Jining No. 1 Peo- ple’s Hospital of Shandong for their support and the patients enrolled in this study.

Compliance with ethical guidelines

Conflict of interest. Y.Huang,X.Liu,X.XuandJ.Liu declarethattheyhavenocompetinginterests.

Allproceduresperformedinstudiesinvolvinghuman participantswereinaccordancewiththeethicalstan- dardsoftheinstitutionaland/ornationalresearch committeeandwiththe1975HelsinkiDeclarationand itslateramendmentsorcomparableethicalstandards. ThisstudywasapprovedbytheEthicsCommittee oftheJiningNo.1People’sHospitalofShandong. Informedconsentwasobtainedfromall individual participantsincludedinthestudy.

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Fachnachrichten

Regensburger Sporttage 2019 Viertageskurs Sportmedizin nach dem neuem Curriculum vom 04.06. bis 07.06.2019

Die 19. Regensburger Sporttage bieten ein abwechslungsreiches sportmedizini- sches Programm mit Top-Referenten und attraktivem Sportpraxis-Teil.

Zum 19. Mal veranstaltet die Orthopädische Universitätsklinik Regensburg am Asklepios Klinikum Bad Abbach in diesem Jahr vom 04.06.–07.06.2018 die „Regensburger Sporttage“.

Im Rahmen der beiden Zweitageskurse 4 und 7 der Deutschen Gesellschaft für Sportmedizin werden Sie im Sinne von Prävention und Rehabilitation mit den Sportarten Bogenschießen, Sportklettern, Radsport, Slackline und Beachvolleyball fit gemacht und auf dem Laufenden gehalten. Die neuesten Trends in der Diagnostik und Therapie werden Ihnen vorgestellt. Ihre praktischen Fähigkeiten in Sonographie, Chirotherapie und Injektionstechniken können Sie in Hands-on-Workshops trainieren. Hierzu stehen Ihnen erfahrene Dozenten und Anwender zur Verfügung. Als Besonderheit wurden auch dieses Jahr wieder renommierte Sportmediziner und Experten

aus dem Spitzensport gewonnen, die Ihnen aus erster Hand über die Behandlung und den Umgang mit den Profisportlern berichten.

Wissenschaftliche Leitung 4 Prof. Dr. med. Dr. h. c. J. Grifka

4 Prof. Dr. med. T. Renkawitz

Anerkennung Der Kurs erfüllt die Anforderungen für die Zweitageskurse 4 und 7 nach dem neuen Curriculum der DGSP zur Erlangung der Zusatzweiterbildung „Sportmedizin‘‘ mit 16 Stunden Theorie und

Praxis der Sportmedizin und 16 Stunden sportmedizinischeAspekte des Sports.

Die Fort- und Weiterbildungsveranstaltungwird bei der BLÄK beantragt. Physiotherapeuten erhalten für jeden Tag der Fortbildungsveranstaltung eine Teilnahmebestä-

tigung über 8 Unterrichtseinheitenentsprechend 8 Fortbildungspunkten.

Anmeldung und Information Orthopädische Universitätsklinikfür die Universität Regensburg Asklepios Klinikum Bad Abbach GmbH

93077 Bad Abbach

Telefon: 09405-182478 Telefax: 09405-182479

E-Mail: [email protected]

www.ur.de/orthopaedie/sporttage

Bildnachweis Chauncey Davis, flickr.com | Holm Engelbrecht, flickr.com | Dean Drobot, shutterstock.com

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