Intraartikuläre Knorpeltherapie Cortison bis PRP (ACP) O ... · Intraartikuläre Knorpeltherapie...

O.Miltner

Friedrichstr.94, 10117 Berlin

D O C O R T H O

PRAXIS FÜR GANZHEITLICHEORTHOPÄDIE & UNFALLCHIRURGIE

Intraartikuläre Knorpeltherapie Cortison bis PRP (ACP)

Schmerzen D O C O R T H O


Implantate Naht

Arthrose

D O C O R T H O


Behandlungsoptionen

Injek&onen

D O C O R T H O


OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis and cartilage 2008; 16: 137-162 Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P. University of Edinburgh, Osteoarticular Research Group, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom. 16 Experten; 2 Kontinenten, 6 Länder; 4 Disziplinen Systematischer Review von 1945-2006; Level of evidence (LoE) Effect size for pain (ES) Strength of recommendation (SOR)

Review

D O C O R T H O


Medikamente

LoE ES (Pain) SOR (%) ------------------------------------------------------------------------------------------------- 1. Paracetamol Knie (bis 4g/Tag) Ia 0,21 92 % 2. Paracetamol Hüfte (bis 4g/Tag) IV 0,21 92 % 3. NSAR ; COX-2 Ia 0,32 93 % 4. Topische NSAR; Capsaicin Ia 0,32 85 % 5.  Glucosamin Ia 0,45 63 % 6.  Chondroitin Ia 0,30 63 % 7.  Glucosaminsulfat / Chondroitinsulfat Ib 41 % 8. Steroide i.a. (Knie) Ia 0,72 78% 9. Steroide i.a.(Hüfte) Ib 0,72 78 % 10. Hyaluronsäure Ia 0,32 64 %

D O C O R T H O


Medikamente

D O C O R T H O


Crawford 2013

Kortison D O C O R T H O


Osteoarthritis and cartilage 2008; 16: 137-162 J Am Acad Orthop Surg. 2009; 638-646

Kortison

Ergebnisse bzgl Knie: •  13 Placebo RCT •  11/13 Guidelines •  Schmerzreduktion: 0,72 (0,42-1,02) •  Dauer 1-3 Wo. •  Schmerzverstärkung nach 4- 24 Wo. •  Funktionsverbesserung n.s. •  Erguß ? •  Triamzinolon vs. Betametason •  4 Spritzen pro Jahr Ergebnisse bzgl. Hüfte: •  2 RCT; •  Kortison vs. Lokale: 3 Mon. Sx-besserung •  Kortison vs. Kochsalz: keine Verbesserung

D O C O R T H O


Hyaluronsäure

Synovialzellen Entzündungszellen Chondrozyten

Neusynthese von HA (Smith & Ghosh)

Regulation der Zellaktivität (Corrado et al.)

Verbesserung des Zellmetabolismus (Guidolin et al.)

Schmerz- und Funktionsverbesserung Miltner et al.

Gelenkknorpel Reduktion des Entzündungsprozess

Verbesserung oberflächliche Schicht Matrix Synthese

Symptomatic slow acting drugs (SYSADOA)

D O C O R T H O


Osteoarthritis and cartilage 2008; 16: 137-162 Rheumatol Int. 2006 Feb;26(4):314-9.

Hyaluronsäure

Ergebnisse bzgl Knie: •  8/9 Guidelines •  22 Placebo RCT •  2 Metaanalyse für RCT signifikante Verbesserung •  1 Metaanalyse für RCT keine Verbesserung •  Schmerzreduktion: 0,32 (0,17-0,47) •  Schmerzreduktionsdauer 2-3 Mon. •  Funktionsverbesserung 6 Mon. •  Wirkungseintritt nach 5-13 Wochen •  Hochmolekulare Hyaluronsäure ist effektiver •  Verbesserter Effekt wenn additiv mit Steroide

Ergebnisse bzgl. Hüfte: •  Kein Unterschied bzgl. Molekulargewicht •  Verbesserung uneinheitlich

D O C O R T H O


Disease modifying OA drugs (DMOAD)

Platelet Rich Plasma(PRP)

D O C O R T H O


Buhr&Siekmann 2009

Indikationen - PRP

Akut:

Achillessehnenrupturen RM-‐rupturen Muskelfaserriß

Kniebandverletzung Mensikusverletzung Knorpelverletzungen

Chronisch:

Tennisellenbogen AS –tendopathie

Patellarsehnenreizung Plantarfaszienreizung Subacromialsyndrom Kleine RM-‐läsionen Knorpelverschleiß

Opera&on: Intraopera&v ACP Postopera&v ACP

Konserva&v: ACP

ACP in Kombina&on mit Therapieformen

-‐ PT /MTT -‐ Hyaluronsäure

D O C O R T H O


PRP

3 7 Chan et al 2006

Optimaler Injektionszeitpunkt

D O C O R T H O


Arthrose D O C O R T H O


Zhu et al. 2013 Review

Basic science and clinical application of platelet-rich plasmafor cartilage defects and osteoarthritis: a review

Q7 Y. Zhu, M. Yuan, H.Y. Meng, A.Y. Wang, Q.Y. Guo, Y. Wang, J. Peng*

Institute of Orthopedics, Chinese PLA General Hospital, Fuxing 28# Road, Beijing 100853, China

a r t i c l e i n f o

Article history:Received 12 June 2013Accepted 30 July 2013

Keywords:Platelet-rich plasmaCartilage defectsOsteoarthritis

s u m m a r y

Cartilage defects (CDs) and the most common joint disease, osteoarthritis (OA), are characterized bydegeneration of the articular cartilage that ultimately leads to joint destruction. Current treatmentstrategies are inadequate: none results in restoration of fully functional hyaline cartilage, for uncertainlong-term prognosis. Tissue engineering of cartilage with auto-cartilage cells or appropriate mesen-chymal stem cell (MSC)-derived cartilage cells is currently being investigated to search for new therapies.Platelet-rich plasma (PRP), an autologous source of factors obtained by centrifugation, possesses variousfunctions. For culture of MSCs and cartilage cells, it might be substituted for fetal bovine serum (FBS)with high efficiency and safety. It enhances the regeneration of cartilage cells when added to cartilagetissue engineering constructs for repairing CDs and as regenerative injection therapy for OA. But chal-lenges also remain. Some of the growth factors (GFs) present in PRP have negative effects on the OA joint.It is therefore unlikely that a mix of GFs some of which have negative effects in the OA joint, as present inPRP, will be of benefit in OA. Future directions of PRP application may concentrate on seeking anappropriate and innocuous agent like anti-VEGF antibody that can modulate and control the effect of PRP.

! 2013 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

Introduction

Articular cartilage damage is usually caused by sports injuries oraccidental trauma and aging. It regularly progresses tomore seriousjoint disorders such as osteoarthritis (OA), necrosis of subchondralbone tissue or arthritis. An estimated 15% of the world’s populationhave joint diseases; more than 39 million people in the EuropeanUnion andmore than 20million Americans have OA. By 2020, thesenumbers will probably be doubled1.

After traumatic or pathological injury, hyaline articular cartilage,the load-bearing tissue of joint, has limited or no intrinsic capacityfor repair capacity, and even minor lesions or injuries may lead toprogressive damage and joint degeneration.

OA is a chronic degenerative joint disease characterized byprogressive destruction of articular cartilage, thinning and eventual

wearing of articular cartilage, thus resulting in painful, limited jointmovement. The degeneration of articular cartilage, mainly due tochanges in the activity of chondrocytes in favor of catabolic activity,which also involves other joint tissues, as alterations of themeniscus, sclerosis and edema in the underlying subchondral boneas well as intermittent inflammation of synovium.

Current treatments for articular cartilage damage, such as sur-gical intervention (microfracture, osteochondral auto- or allo-grafts), to repair articular cartilage are less than satisfactory andrarely restore full function. To obtain sufficient chondrocytes fortherapy, the required in vitro expansion usually induces cartilagecell dedifferentiation. Tissue engineering-based cartilage repair hasbeen pursued to provide more functional biological tissue. Thechondrocytes are taken from non-weight-bearing parts of intactjoint areas and expanded in cell culture, then transplanted into thedefective areas of the affected joints. Clinical trials of autologouschondrocyte implantation (ACI) have shown promise2.

Multipotent adult mesenchymal stem cells (MSCs) can differ-entiate into cells of the chondrogenic lineage and are isolated froma wide variety of tissue sources; they are easy to isolate withoutsignificant donor-site morbidity and are easier to expand in vitrothan chondrocytes3. These cells are also used for cartilage tissueengineering and chronic degenerative disorders and to preventcartilage degradation in OA because of their trophic/regenerative

Abbreviations: ATP, adenosine triphosphate; EGF, epidermal growth factor; KGF,keratinocyte growth factor; L-PRP, leukocyte-rich platelet-rich plasmaQ1Q2

* Address correspondence and reprint requests to: J. Peng, Institute of Orthope-dics, Chinese PLA General Hospital, Fuxing 28# Road, Beijing, China.Tel: 86 13910060749.

E-mail addresses: [email protected], [email protected] (J. Peng).

1063-4584/$ e see front matter ! 2013 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.http://dx.doi.org/10.1016/j.joca.2013.07.017

Osteoarthritis and Cartilage xxx (2013) 1e11

12345678910111213141516171819202122232425262728293031323334353637383940414243444546474849505152535455

5657585960616263646566676869707172737475767778798081828384858687888990919293949596979899

100101102103104105106107108109110

YJOCA2956_proof ! 17 August 2013 ! 1/11

Please cite this article in press as: Zhu Y, et al., Basic science and clinical application of platelet-rich plasma for cartilage defects andosteoarthritis: a review, Osteoarthritis and Cartilage (2013), http://dx.doi.org/10.1016/j.joca.2013.07.017

carrier to help the defect heal itself has been of interest23. Recently,experimental study has identified the effects of PRP on OA in ani-mal models such as rats24,25 and rabbits26e29. PRP has become anoptimal candidate agent for OA because of its milieu of GFs, it iseasily obtained and prepared. The effects of PRP include fewpostoperative complications, alleviating pain, antimicrobial effectsand anti-inflammatory effects30. Its initial inhibition of macrophageproliferation may explain this phenomenon.

In an OA model induced by formalin, collagenase, or anteriorcruciate ligament transfection, treatment with PRP/gelatin hydro-gel injected in knee joints increased mRNA expression of proteo-glycan core protein in the articular cartilage and decreasedchondrocyte apoptosis24 and suppressed progression of OA28. The

effects were related to severity of OA27. PRP combined with stemcells injected into knees increased col-II content and decreasedchondrocyte apoptosis24 The most common PRP application is in-jection, which avoids the adverse effects of surgery.

In addition, with osteoarthritic chondrocytes cultured in thepresence of IL-1 to mimic the osteoarthritic environment, PRP candiminished multiple inflammatory IL-1 mediated effects. It hasanalgesic, antibacterial, anti-inflammatory activity; balances jointangiogenesis, coagulation and hemostasis; increases GAG level; andstimulates chondrocyte synthesis cartilage matrix, for stem orprimary cell migration, differentiation, as well as wound healing.PRP may become an attractive candidate to remedy and protectagainst cartilage degeneration in OA.

Fig. 2. Chondrocytes expansion in vitro.

Table IPRP application in vitro

Cell type Classification of PRP58 PRP application to culture Outcome Reference

a. PRP for chondrocyte cultureHuman chondrocytes P2-x-NA Cells seeded on gelatin microcarriers

sealed with PRPImprove cell proliferation and ECM synthetizeand maintain cell phenotype

59

Porcine chondrocytes P3-x-Aa 10% PRP release in serum-free medium Improve cell proliferation and matrix biosynthesis,PG and collagen synthesis

60

Human chondrocytes P4-B In mono- and 3-D cultures Improve cell proliferation and ECM synthetize andmaintain cell phenotype

61

New Zealand white rabbitchondrocytes

P4-NA 20% PRP in DMEM Improve cell proliferation and increase aggrecan,BMP-2, BMP7, col-II expression in the long-term

62

Japanese white rabbitchondrocytes

P4-x-NA 3% PRP with alginate beads Increase chondrocyte GAG synthesis and maintaincell phenotype.

28

Human articular chondrocytes NA-x-Bb In mono- and 3-D cultures Improve chondrocyte proliferation but reducetype II collagen, aggrecan and BMP-2

17

Bovine articular chondrocytes NA-x-Bb In mono- and 3-D cultures Improve chondrocyte proliferation but reducetype II collagen, increase type I collagen

18

b. PRP for MSC cultureHuman mesenchymal

stem cell (HMSC)P2-Aa 10% PRP in DMEM Improve cell proliferation and induce

chondrogenesis

63

BM-HMSCs NAeNA 10% HPL Improve cell proliferation 64

BM-HMSCs P3-NA 5% HPL Improve cell proliferation and decreasealloantigen-induced cytotoxic activity

20

BM-HMSCs P3eB 10% HPL Improve cell proliferation, preserve phenotype anddifferentiation capacity

65,66

BM-HMSCs P2-x-Bb 10% PRP Improve cell proliferation and migration 67

Human subchondralprogenitor cells

P4-NA-B 5% PRP Improve cell proliferation and induce chondrogenesis 68

Human adiposetissue-derived MSCs

P4-x-NA 10% PRP Improve cell proliferation, preserves differentiationcapacity and immunophenotype

69

Mouse muscle-derivedstem cell (MDSC)

P3-x-NA 10% PRP Improve cell proliferation and upregulatetype II collagen

70

Nude rats MDSC P2-NA Pellet culture added PRP combined witha VEGF antagonist and BMP-4

Increase type II collagen 24

Sheep MDSC NA-x-NA High-density micromass culture in PRP Improve cell proliferation 71

Human BMSC P3-NA Pellet culture with 5% HPL Increased cell proliferation formed evident andclear cartilage

72

P1, P2, P3, P4 represent platelet concentrations (platelets/mL): P1, !baseline levels; P2, >baseline levels to 750,000; P3, 750,000e1,250,000; and P4, >1,250,000. Endogenousactivation has no designation. If an exogenous external activator is used, it is documentedwith an x. Total leukocyte content in buffy coat is identified as A,>baseline level, or B,!baseline levels; neutrophil count is identified as a, >baseline level, or b, !baseline levels. NA, not applicable.

Y. Zhu et al. / Osteoarthritis and Cartilage xxx (2013) 1e114

371372373374375376377378379380381382383384385386387388389390391392393394395396397398399400401402403404405406407408409410411412413414415416417418419420421422423424425426427428429430431432433434435

436437438439440441442443444445446447448449450451452453454455456457458459460461462463464465466467468469470471472473474475476477478479480481482483484485486487488489490491492493494495496497498499500



carrier to help the defect heal itself has been of interest23. Recently,experimental study has identified the effects of PRP on OA in ani-mal models such as rats24,25 and rabbits26e29. PRP has become anoptimal candidate agent for OA because of its milieu of GFs, it iseasily obtained and prepared. The effects of PRP include fewpostoperative complications, alleviating pain, antimicrobial effectsand anti-inflammatory effects30. Its initial inhibition of macrophageproliferation may explain this phenomenon.

In an OA model induced by formalin, collagenase, or anteriorcruciate ligament transfection, treatment with PRP/gelatin hydro-gel injected in knee joints increased mRNA expression of proteo-glycan core protein in the articular cartilage and decreasedchondrocyte apoptosis24 and suppressed progression of OA28. The

effects were related to severity of OA27. PRP combined with stemcells injected into knees increased col-II content and decreasedchondrocyte apoptosis24 The most common PRP application is in-jection, which avoids the adverse effects of surgery.

In addition, with osteoarthritic chondrocytes cultured in thepresence of IL-1 to mimic the osteoarthritic environment, PRP candiminished multiple inflammatory IL-1 mediated effects. It hasanalgesic, antibacterial, anti-inflammatory activity; balances jointangiogenesis, coagulation and hemostasis; increases GAG level; andstimulates chondrocyte synthesis cartilage matrix, for stem orprimary cell migration, differentiation, as well as wound healing.PRP may become an attractive candidate to remedy and protectagainst cartilage degeneration in OA.

Fig. 2. Chondrocytes expansion in vitro.

Table IPRP application in vitro

Cell type Classification of PRP58 PRP application to culture Outcome Reference

a. PRP for chondrocyte cultureHuman chondrocytes P2-x-NA Cells seeded on gelatin microcarriers

sealed with PRPImprove cell proliferation and ECM synthetizeand maintain cell phenotype

59

Porcine chondrocytes P3-x-Aa 10% PRP release in serum-free medium Improve cell proliferation and matrix biosynthesis,PG and collagen synthesis

60

Human chondrocytes P4-B In mono- and 3-D cultures Improve cell proliferation and ECM synthetize andmaintain cell phenotype

61

New Zealand white rabbitchondrocytes

P4-NA 20% PRP in DMEM Improve cell proliferation and increase aggrecan,BMP-2, BMP7, col-II expression in the long-term

62

Japanese white rabbitchondrocytes

P4-x-NA 3% PRP with alginate beads Increase chondrocyte GAG synthesis and maintaincell phenotype.

28

Human articular chondrocytes NA-x-Bb In mono- and 3-D cultures Improve chondrocyte proliferation but reducetype II collagen, aggrecan and BMP-2

17

Bovine articular chondrocytes NA-x-Bb In mono- and 3-D cultures Improve chondrocyte proliferation but reducetype II collagen, increase type I collagen

18

b. PRP for MSC cultureHuman mesenchymal

stem cell (HMSC)P2-Aa 10% PRP in DMEM Improve cell proliferation and induce

chondrogenesis

63

BM-HMSCs NAeNA 10% HPL Improve cell proliferation 64

BM-HMSCs P3-NA 5% HPL Improve cell proliferation and decreasealloantigen-induced cytotoxic activity

20

BM-HMSCs P3eB 10% HPL Improve cell proliferation, preserve phenotype anddifferentiation capacity

65,66

BM-HMSCs P2-x-Bb 10% PRP Improve cell proliferation and migration 67

Human subchondralprogenitor cells

P4-NA-B 5% PRP Improve cell proliferation and induce chondrogenesis 68

Human adiposetissue-derived MSCs

P4-x-NA 10% PRP Improve cell proliferation, preserves differentiationcapacity and immunophenotype

69

Mouse muscle-derivedstem cell (MDSC)

P3-x-NA 10% PRP Improve cell proliferation and upregulatetype II collagen

70

Nude rats MDSC P2-NA Pellet culture added PRP combined witha VEGF antagonist and BMP-4

Increase type II collagen 24

Sheep MDSC NA-x-NA High-density micromass culture in PRP Improve cell proliferation 71

Human BMSC P3-NA Pellet culture with 5% HPL Increased cell proliferation formed evident andclear cartilage

72

P1, P2, P3, P4 represent platelet concentrations (platelets/mL): P1, !baseline levels; P2, >baseline levels to 750,000; P3, 750,000e1,250,000; and P4, >1,250,000. Endogenousactivation has no designation. If an exogenous external activator is used, it is documentedwith an x. Total leukocyte content in buffy coat is identified as A,>baseline level, or B,!baseline levels; neutrophil count is identified as a, >baseline level, or b, !baseline levels. NA, not applicable.


371372373374375376377378379380381382383384385386387388389390391392393394395396397398399400401402403404405406407408409410411412413414415416417418419420421422423424425426427428429430431432433434435

436437438439440441442443444445446447448449450451452453454455456457458459460461462463464465466467468469470471472473474475476477478479480481482483484485486487488489490491492493494495496497498499500



Anaboler Effekt auf Chondrocyten Verbesserung Zell- und Matrixproliferation Antiinflammatorischer Effekt

Arthrose

-+,.?1-%+ ,"-&("-)I `7=7Z9MW69Z#ZWK57=I :V67=5:#B9M#ZW9KM#C#`7=MVKE#_95=#76#KdWZZ5=Q#78#MVW#b=WW

I 5`9Q5=Q#85=[5=QK#BS#"9e#76#*"-E###78#[WQW=W69M5gW#:V9=QWK

,%*!)")&-F(#1&?0;#

!)&-(+&#1(.(,&-%+kO#_9M5W=MK#2 !4"4!4########kO#_9M5W=MK#2 .7d#*7ZW:NZ96#AW5QVM#'4)4########kO#_9M5W=MK#2 '5QV#*7ZW:NZ96#AW5QVM#'4)4

Kon – AAOS 2011

D O C O R T H O


Arthrose !"%1!(,&-F(#,%*!)")&-F(#1&?0;#

-<0,#KNcaW:M5gW

\#*%+&'1I !4"4!4#q#.4A#'4)#B=4K4EI !4"4!4#r#'4A#'4)#B_qO4OOTE

R#*%+&'1I !4"4!4#r#.4A#'4)#B_qO4OOYEI !4"4!4#r#'4A#'4)#B_qO4OOkE

*"

&"

,"

!"

$"

+"

'"

48: *C $C

4P4GQ(R?RQ(R?

(G#F)1

*"

&"

,"

!"

$"

+"

'"

48: *C $C

4P4GQ(R?RQ(R?

Kon – AAOS 2011

D O C O R T H O


Arthrose 0(/(+(")&-%+#"(.)&(0#"(1?.&1#

A%"1&#"(1?.&1$%"#'-/'("#0(/"((

%$#<+((#0(/(+(")&-%+#$%"#)..#&"()&*(+&1

1-*-.)"#"(1?.&1#)&#\#`#$%"#!4"4!4#)+0#.4A4#'4)4

Kon – AAOS 2011

D O C O R T H O


Arthrose

! !4"4!L#$?"&'("#-*!"%F(*(+&#$%"#,)"&-.)/(#0(/(+(")&-%+

0(/(+(")&-%+#"(.)&(0#"(1?.&1\2R#`7=MVK#

Kon – AAOS 2011

D O C O R T H O


Arthrose )/(#"(.)&(0#"(1?.&1#

;%?+/#!)&-(+&1#-+#!"!#/"%?!#,%+&-+?(#&%#-*!"%F(#$"%*#\#&%#R#*%+&'1#

!"

!#

#"

##

$"

$#

%"

%#

&'( )* $*

MSTH

+&,-.,#",/(0'1,232.4('#",/(0'1,232+&,-.,#",/(0'1,56,78.4(',#",/(0'1,56,78

s#kO#;()"1#\#`L !4"4!4#q#.4A#'4)#R#`L !4"4!4#r#.4A#'4)#B_qO4OOJE

r#kO#;()"1\#`L !4"4!4#q#.4A#'4)#R#`L !4"4!4#q#.4A#'4)

+%#1-/+-$-,)+&#0-$$("(+,(#$%"#%.0("#!)&-(+&1#3(&A((+#\#/"%?!1

Kon – AAOS 2011

D O C O R T H O




http://ajs.sagepub.com/Medicine

The American Journal of Sports

http://ajs.sagepub.com/content/40/12/2822The online version of this article can be found at:

DOI: 10.1177/0363546512461902

2012 40: 2822 originally published online October 25, 2012Am J Sports MedBiasi and Michele Ciuffreda

Fabio Cerza, Stefano Carnì, Alessandro Carcangiu, Igino Di Vavo, Valerio Schiavilla, Andrea Pecora, Giuseppe DeTreatment of Gonarthrosis

Comparison Between Hyaluronic Acid and Platelet-Rich Plasma, Intra-articular Infiltration in the

Published by:

http://www.sagepublications.com

On behalf of:

American Orthopaedic Society for Sports Medicine

can be found at:The American Journal of Sports MedicineAdditional services and information for

http://ajs.sagepub.com/cgi/alertsEmail Alerts:

http://ajs.sagepub.com/subscriptionsSubscriptions:

http://www.sagepub.com/journalsReprints.navReprints:

http://www.sagepub.com/journalsPermissions.navPermissions:

What is This?

- Oct 25, 2012OnlineFirst Version of Record

- Nov 28, 2012Version of Record >>

by Oliver Miltner on December 29, 2012ajs.sagepub.comDownloaded from



up to 93% of cases.15 The patient was placed in a supineposition, the knee being slightly bent with the help of a pop-liteal cushion. The medial, lateral, and superior edges of thepatella were always marked. After local anesthesia withlidocaine chlorohydrate, a superolateral approach wasused whereby the needle was inserted at an angle of approx-imately 45! toward the medial joint line of the knee untilreaching the ‘‘soft spot’’ between the patella and the femur,next to the junction of the line going through the lateralpatellar edge and the line going through the superior poleof the patella. Before the drug was injected, the piston ofthe syringe was drawn back slightly to ensure that the nee-dle was properly in the joint. The mean volume of ACPinjected in our series was 5.5 mL for each infiltration.

After the infiltration, the patients were monitored for10 minutes to ensure there were no adverse reactions.None were observed in our series. Postinjection protocoldid not provide any restriction of physical activity. Allthe patients were evaluated before the infiltration and at4, 12, and 24 weeks after the first injection. The WesternOntario and McMaster (WOMAC) osteoarthritis indexquestionnaire2 was used, which assesses pain, articularstiffness, and functional limitation. This step was managedby the same operator. For WOMAC, the minimum score iszero and the maximum score, which represents the highestgrade of debilitation, is 96.

The minimal detectable change was 1 and the minimalclinically important difference was 3.

Statistical Analysis

The significance of differences among the periods post-treatment (intragroup analysis) was tested by analysis ofvariance with Bonferroni correction. To test the

significance between the 2 types of treatment (intergroupanalysis), we conducted a t test on groups of data belongingto the same level of pathologic changes and at the sameposttreatment period.

With an anticipated effect size of 0.8 and a desired sta-tistical power level of 0.8, we calculated a minimum samplesize of 66 patients (33 patients per group).

RESULTS

No patients withdrew during the study period.The ACP group consisted of 25 men and 35 women, with

a mean age of 66.5 years (range, 31-90 years; standarddeviation [SD], 11.3 years). Gonarthrosis was primary in57 patients and was secondary to a trauma in 3 patients(lesion of cartilage due to repetitive traumas during sportin 2 patients; lesion of cartilage due to a fall in 1 patient).The pretreatment mean WOMAC score was 76.9 (range,55-94; SD, 9.5). The patients were graded according tothe Kellgren-Lawrence radiographic classification: 21patients had grade I gonarthrosis, 24 had grade II, and15 had grade III. The condition affected the right knee in43 patients and the left knee in 17 patients.

The HA group consisted of 28 men and 32 women, witha mean age of 66.2 years (range, 36-87 years; SD, 10.6years). In this group, gonarthrosis was primary in 59patients and secondary to a trauma in 1 patient (fractureof the tibial plateau). The pretreatment mean WOMACscore was 75.4 (range, 54-91; SD, 10.7). The patientswere graded again by the Kellgren-Lawrence classifica-tion: 25 patients had grade I gonarthrosis, 22 had gradeII, and 13 had grade III. The condition affected the rightknee in 48 patients and the left knee in 12 patients.

Assessed for eligibility (n=123)

Excluded (n=3)! Not meeting inclusion criteria (n=2)! Declined to participate (n=1)! Other reasons (n=0)

Analyzed (n=60)Excluded from analysis (n=0)

Lost to follow-up (n=0)Discontinued intervention (n=0)

Allocated to receive ACP infiltration (n=60)! Received allocated intervention (n=60)! Did not receive allocated intervention (n=0)

Lost to follow-up (n=0)Discontinued intervention (n=0)

Allocated to receive HA infiltration (n=60)! Received allocated intervention (n=60)! Did not receive allocated intervention (n=0)

Analyzed (n=60)Excluded from analysis (n=0)

Allocation

Analysis

Follow-up

Randomized (n=120)

Enrollment

Figure 1. Flow diagram of the study. ACP, autologous conditioned plasma; HA, hyaluronic acid.

2824 Cerza et al The American Journal of Sports Medicine




There was no statistical difference in the age of thepatients (P . .05). The percentage of men to women wassimilar between the 2 groups (ACP group: 42% men vsHA group: 47% men) with no statistically significant differ-ence (P . .05). The distribution of gonarthrosis was alsosimilar between the groups (ACP group: 35% grade I,40% grade II, 25% grade III vs HA group: 42% grade I,37% grade II, 21% grade III) with no statistically signifi-cant difference (P . .05). Demographic information isreported in Table 1. Finally, there was no statistical differ-ence in pretreatment WOMAC scores (P = .557).

At week 4, both groups showed a significant reductionin the overall WOMAC score compared with baseline inboth groups (Figure 2). The mean WOMAC score was49.6 (range, 5-80; SD, 617.7) in the ACP group versus55.2 (range, 25-78; SD, 612.3) in the HA group. The differ-ence recorded between the ACP and the HA groups wasstatistically significant (P \ .001) at this time point.

At week 12, a reverse trend was observed, with a contin-uous improvement in the patients treated with PRP anda slight worsening in patients treated with HA, as seenin Figure 3. The mean WOMAC score was 39.1 (range,5-76; SD, 617.8) in the ACP group versus 57.0 (range,32-78; SD, 611.7) in the HA group. The difference recordedbetween the groups was statistically significant (P \ .001).

In both groups the score was significantly better than base-line at week 12.

At week 24, the subjects treated with PRP showed a con-tinuous improvement, whereas the subjects treated withHA showed a sharp worsening, as seen in Figure 4. Foursubjects in the HA group regressed to their baselineWOMAC scores. Although the mean WOMAC score was36.5 in the ACP group (range, 5-76; SD, 617.9), it was65.1 in the HA group (range, 41-82; SD, 610.6). The differ-ence recorded between the groups was statistically signifi-cant (P \ .001).

In both groups, the score was significantly better thanbaseline at week 24.

In the ACP group, there were significant differencesbetween pretreatment and all follow-up time points (4weeks P \ .001, 12 weeks P \ .001, and 24 weeks P \.001). In addition, there were significant differencesbetween 4 and 12 weeks (P \ .001) and between 4 and24 weeks (P \ .001). There was no difference between 12and 24 weeks (P = .007).

TABLE 1Demographic Informationa

ACP Group HA Group

Average age (SD), y 66.5 (11.3) 66.2 (10.6)Male patients, No. (%) 25 (42) 28 (47)Female patients, No. (%) 35 (58) 32 (53)Left knee, No. 17 12Right knee, No. 43 48Gonarthrosis, No. (%)

Grade I 21 (35) 25 (42)Grade II 24 (40) 22 (37)Grade III 15 (25) 13 (21)

aACP, autologous conditioned plasma; HA, hyaluronic acid; SD,standard deviation.

Pretreatment4 wks

Pos!reatment 12 wks Pos!reatment 24 wks

Pos!reatment

73

42

3230

77

51

4139

79

57

4341

Grade I Grade II Grade III

Figure 2. Mean Western Ontario and McMaster (WOMAC)scores for the autologous conditioned plasma (ACP) groupin relation to degree of gonarthrosis.

Pretreatment4 wks


Pos!reatment

70

4951

59

74

57 57 65

85

65 67 75


Figure 3. Mean Western Ontario and McMaster (WOMAC)scores for the hyaluronic acid (HA) group in relation to degreeof gonarthrosis.

79.6 49.6 39.1 36.575.4 55.2 57.0 65.10

10

20

30

40

50

60

70

80

90

100

Pretreatment 4 wks Posttreatment

12 wks Posttreatment


WO

MAC

Sco

re

ACP GroupHyaluronic Acid Group

Figure 4. Mean Western Ontario and McMaster (WOMAC)scores for the autologous conditioned plasma (ACP) andhyaluronic acid (HA) groups.

Vol. 40, No. 12, 2012 Comparison Between HA and PRP in Gonarthrosis 2825












ACP Group HA Group




Pretreatment4 wks


Pos!reatment

73

42

3230

77

51

4139

79

57

4341



Pretreatment4 wks


Pos!reatment

70

4951

59

74

57 57 65

85

65 67 75



79.6 49.6 39.1 36.575.4 55.2 57.0 65.10

10

20

30

40

50

60

70

80

90

100




WO

MAC

Sco

re













ACP Group HA Group




Pretreatment4 wks


Pos!reatment

73

42

3230

77

51

4139

79

57

4341



Pretreatment4 wks


Pos!reatment

70

4951

59

74

57 57 65

85

65 67 75



79.6 49.6 39.1 36.575.4 55.2 57.0 65.10

10

20

30

40

50

60

70

80

90

100




WO

MAC

Sco

re















ACP Group HA Group




Pretreatment4 wks


Pos!reatment

73

42

3230

77

51

4139

79

57

4341



Pretreatment4 wks


Pos!reatment

70

4951

59

74

57 57 65

85

65 67 75



79.6 49.6 39.1 36.575.4 55.2 57.0 65.10

10

20

30

40

50

60

70

80

90

100




WO

MAC

Sco

re







Comparison Between Hyaluronic Acidand Platelet-Rich Plasma, Intra-articularInfiltration in the Treatment of Gonarthrosis

Fabio Cerza,*y MD, Stefano Carnı̀,z MD, Alessandro Carcangiu,*§ MD,Igino Di Vavo,* MD, Valerio Schiavilla,* MD, Andrea Pecora,* MD,Giuseppe De Biasi,|| and Michele Ciuffreda||

Investigation performed at the Paolo Colombo Hospital of Velletri, Rome, Italy

Background: Arthrosis is particularly prevalent in the knee. Infiltration treatment for gonarthrosis is among the most widely usedtechniques in orthopaedic practice.

Purpose: To compare the clinical response of hyaluronic acid (HA) and platelet-rich plasma (PRP) treatment in 2 groups of pa-tients affected by gonarthrosis.

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: A total of 120 patients affected by clinically and radiographically documented gonarthrosis were included in this study.The gonarthrosis was graded using the Kellgren-Lawrence radiographic classification scale. The 120 patients were randomizedinto 2 study groups in a 1:1 ratio: 60 patients received 4 intra-articular injections of PRP (specifically, autologous conditionedplasma [ACP], 5.5 mL), and 60 patients received 4 intra-articular injections of HA (20 mg/2 mL). An unblinded physician performedinfiltration once a week for 4 weeks into the knee affected by clinically relevant gonarthrosis (in both groups). All patients wereevaluated with the Western Ontario and McMaster (WOMAC) score before the infiltration and at 4, 12, and 24 weeks after thefirst injection.

Results: Treatment with a local injection of ACP had a significant effect shortly after the final infiltration and a continuouslyimproving sustained effect up to 24 weeks (WOMAC score, 65.1 and 36.5 in the HA and ACP groups, respectively; P \ .001),where the clinical outcomes were better compared with the results with HA. In the HA group, the worst results were obtainedfor grade III gonarthrosis, whereas the clinical results obtained in the ACP group did not show any statistically significant differ-ence in terms of the grade of gonarthrosis. The mean WOMAC scores for grade III gonarthrosis were 74.85 in the HA group and41.20 in the ACP group (P \ .001).

Conclusion: Treatment with ACP showed a significantly better clinical outcome than did treatment with HA, with sustained lowerWOMAC scores. Treatment with HA did not seem to be effective in the patients with grade III gonarthrosis.

Keywords: platelet-rich plasma; hyaluronic acid; gonarthrosis; intra-articular infiltration

Four million Italians suffer from arthrosis, which mostlyaffects the knee and can be quite debilitating.6 Men aremore often affected than women in populations younger

than 50 years. Beyond 65 years of age, however, womenare affected twice as much as men, a fact that may beattributable to menopause.22 Gonarthrosis is a conditionthat affects the articular cartilage, synovial membrane,and subchondral bone. Cartilage cells, called chondrocytes,occupy 1% of the overall volume and produce the extracel-lular matrix, which is mainly composed of collagen II, pro-teoglycans, and glycosaminoglycans. The subchondralbone tissue, synovial membrane, and cartilage are equallyimportant and are responsible for the biochemical and bio-mechanical balance of the joints.25 Previously, joint over-loading and mechanical stress were considered to be themain etiopathogenetic factors in the development ofarthrosis. However, during the past few decades, increasedemphasis has been placed on the biochemical balancerequired for the health of the cartilage. This balance canbe improved by controlling the biochemical factors thatinhibit metalloproteases (interleukin-4, interleukin-10,

§Address correspondence to Alessandro Carcangiu, Orthopaedicsand Traumatology Unit of P. Colombo Hospital of Velletri, Vicolo dell’An-nunziatella, 50 Rome, Italy, 00142 (e-mail: [email protected]).

*Orthopaedics and Traumatology Unit of P. Colombo Hospital of Vel-letri, Rome, Italy.

yOrthopaedic and Sport Traumatology Unit of Villa Salaria PrivateHospital, Rome, Italy.

zUniversity of Rome Campus Biomedico, Rome, Italy.||Transfusional Unit of Paolo Colombo Hospital of Velletri, Rome, Italy.The authors declared that they have no conflicts of interest in the

authorship and publication of this contribution.

The American Journal of Sports Medicine, Vol. 40, No. 12DOI: 10.1177/0363546512461902! 2012 The Author(s)

2822 by Oliver Miltner on December 29, 2012ajs.sagepub.comDownloaded from

Comparison Between Hyaluronic Acidand Platelet-Rich Plasma, Intra-articularInfiltration in the Treatment of Gonarthrosis

Fabio Cerza,*y MD, Stefano Carnı̀,z MD, Alessandro Carcangiu,*§ MD,Igino Di Vavo,* MD, Valerio Schiavilla,* MD, Andrea Pecora,* MD,Giuseppe De Biasi,|| and Michele Ciuffreda||

Investigation performed at the Paolo Colombo Hospital of Velletri, Rome, Italy

Background: Arthrosis is particularly prevalent in the knee. Infiltration treatment for gonarthrosis is among the most widely usedtechniques in orthopaedic practice.

Purpose: To compare the clinical response of hyaluronic acid (HA) and platelet-rich plasma (PRP) treatment in 2 groups of pa-tients affected by gonarthrosis.

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: A total of 120 patients affected by clinically and radiographically documented gonarthrosis were included in this study.The gonarthrosis was graded using the Kellgren-Lawrence radiographic classification scale. The 120 patients were randomizedinto 2 study groups in a 1:1 ratio: 60 patients received 4 intra-articular injections of PRP (specifically, autologous conditionedplasma [ACP], 5.5 mL), and 60 patients received 4 intra-articular injections of HA (20 mg/2 mL). An unblinded physician performedinfiltration once a week for 4 weeks into the knee affected by clinically relevant gonarthrosis (in both groups). All patients wereevaluated with the Western Ontario and McMaster (WOMAC) score before the infiltration and at 4, 12, and 24 weeks after thefirst injection.

Results: Treatment with a local injection of ACP had a significant effect shortly after the final infiltration and a continuouslyimproving sustained effect up to 24 weeks (WOMAC score, 65.1 and 36.5 in the HA and ACP groups, respectively; P \ .001),where the clinical outcomes were better compared with the results with HA. In the HA group, the worst results were obtainedfor grade III gonarthrosis, whereas the clinical results obtained in the ACP group did not show any statistically significant differ-ence in terms of the grade of gonarthrosis. The mean WOMAC scores for grade III gonarthrosis were 74.85 in the HA group and41.20 in the ACP group (P \ .001).

Conclusion: Treatment with ACP showed a significantly better clinical outcome than did treatment with HA, with sustained lowerWOMAC scores. Treatment with HA did not seem to be effective in the patients with grade III gonarthrosis.

Keywords: platelet-rich plasma; hyaluronic acid; gonarthrosis; intra-articular infiltration

Four million Italians suffer from arthrosis, which mostlyaffects the knee and can be quite debilitating.6 Men aremore often affected than women in populations younger

than 50 years. Beyond 65 years of age, however, womenare affected twice as much as men, a fact that may beattributable to menopause.22 Gonarthrosis is a conditionthat affects the articular cartilage, synovial membrane,and subchondral bone. Cartilage cells, called chondrocytes,occupy 1% of the overall volume and produce the extracel-lular matrix, which is mainly composed of collagen II, pro-teoglycans, and glycosaminoglycans. The subchondralbone tissue, synovial membrane, and cartilage are equallyimportant and are responsible for the biochemical and bio-mechanical balance of the joints.25 Previously, joint over-loading and mechanical stress were considered to be themain etiopathogenetic factors in the development ofarthrosis. However, during the past few decades, increasedemphasis has been placed on the biochemical balancerequired for the health of the cartilage. This balance canbe improved by controlling the biochemical factors thatinhibit metalloproteases (interleukin-4, interleukin-10,

§Address correspondence to Alessandro Carcangiu, Orthopaedicsand Traumatology Unit of P. Colombo Hospital of Velletri, Vicolo dell’An-nunziatella, 50 Rome, Italy, 00142 (e-mail: [email protected]).

*Orthopaedics and Traumatology Unit of P. Colombo Hospital of Vel-letri, Rome, Italy.

yOrthopaedic and Sport Traumatology Unit of Villa Salaria PrivateHospital, Rome, Italy.

zUniversity of Rome Campus Biomedico, Rome, Italy.||Transfusional Unit of Paolo Colombo Hospital of Velletri, Rome, Italy.The authors declared that they have no conflicts of interest in the

authorship and publication of this contribution.

The American Journal of Sports Medicine, Vol. 40, No. 12DOI: 10.1177/0363546512461902! 2012 The Author(s)

2822 by Oliver Miltner on December 29, 2012ajs.sagepub.comDownloaded from

Arthrose

Autor Behandlung Type of study Level of evidence

Anzahl Patienten

Ergebnis

Patel (2012) PRP vs. Placebo

Prospective Double-blind randomized study

Level 1 PRP group (n=52)/(n=50) NACL (n=46)

WOMAC (**) 1 Inj = 2 Inj PRP

Spakova (2012)

PRP vs HA

Prospective Cohort study

Level 1 PRP group (n=60) HA (n=60)

Western Ontario (**) VAS (**) 3 Inj

Filardo (2012) PRP vs HA

Double blind randomized controlled study

Level 1 PRP group (n=54) HA (n=55)

IKDC VAS Tegner KOOS Nach 1 J (**)

D O C O R T H O




PRP with a collagen scaffold in tissue engineering can improvebone-marroweinitiated cartilage repair and stimulate the repair oflarge articular cartilage in animal models29. Also, hydrogel com-bined with chondrocytes and PRP may be an ideal environment forproliferation and maturation of articular chondrocytes50. MACTwith PRP can improve cartilage repair in animal models. The samegroup started the clinical application in 81 patients with osteo-chondral lesions; the American Orthopaedic Foot and Ankle Societyscore was improved and expression of col-II and proteoglycanincreased after 4 years51.

Safety of PRP treatment

PRP has antimicrobial effects in vitro30; it inhibits macrophageproliferation and reduces the inflammatory response52. AutologousPRP was found safe for treating knee, foot and ankle lesions in 634patients53 and for articular cartilage degeneration54. No side effectshave been reported. In 261 patients, no adverse effects were foundfollowing injection of PRP-fibrin glue into the knee joint at 6months55.

Many studies have suggested safety, pain relief, and functionalimprovements with PRP injections for OA; adverse effects are rarerisks, and benefits have been thoroughly reviewed. Risks andbenefits are similar to any other intra-articular or peri-articularinjection; adverse effects include infection, bleeding, bruising, pe-ripheral nerve injury, allergy to local anesthetics, and temporaryexacerbation of stiffness and soreness that may last from 2 to 7days56.

Conclusions

Platelet products such as PRP, HPL and platelet supernatants,which can be activated by endogenous or exogenous activators,have high efficiency and multiple functions. Because of the autog-enous source, PRP is easy and convenient to extract, and processingis relatively simple and short; it features high-speed recovery po-tential, easy handling and offers multiple GFs at relatively inex-pensive cost. Above all, its use is safe.

Basic science, preclinical, and clinical studies collectively indi-cate that PRP is promising for treating cartilage injuries and jointpain. PRP in a culture environment has an anabolic effect onchondrocytes and bone-marrow derived stem cells with resultingincreases in cell proliferation and matrix production as well as ananti-inflammatory effect via downregulation of known catabolicsignaling pathways. It may be a feasible, secure, and economic wayto induce MSC differentiation into chondrocytes integrally andexpand cartilage cells in vitro. It is a more economic and effectiveculture medium substitute for FBS. When added on scaffolds ofcartilage tissue-engineered constructs, it can enhance the regen-eration of cartilage cells and repair CDs. The application of PRP forOA in clinical trials has shown promising short-term results (1e2years), although most of these studies were not randomizedcontrolled trials.

However, challenges remain (Table IV). First, platelet qualityinfluences effectiveness, including platelet content, leukocytes andGF concentration, because preparations of PRP have no selectioncriterion. Platelet count in PRP may vary from two- to several-folddepending on the donor’s physical condition, age or gender, whichleads to unstable and non-repeatable PRP treatment. Some of theGFs present in PRP such as TGF-beta and bFGF have negative effectson the OA joint which differ from effects in more normal joints.Because of multifunctional GF effects, chondrogenesis of MSCs orchondrocytes expanded in vitro may not retain the chondrocytephenotype, such as expression of Col-I instead of type II, simulta-neous hypertrophy and bone marker expression. So directedstimulation of GFs might be considered in MSCs and chondrocyteculture to maintain the chondrocyte phenotype. When several GFsexist simultaneously, it might inhibit chondrogenesis effect, such asVEGF and bone morphogenetic protein 2. Impairing osteogenesisby PRP via mutual cooperationwith other biological molecules mayprovide new ways that are prompt, stable, and controllable formaintaining cartilage morphologic features or to promote chon-drogenic differentiation.

Second, with the wide range of methodologies used in eachstudy and the numerous ways to prepare PRP, we cannot providefirm recommendations regarding the type of PRP to use and forwhat indications. Themethods of platelet application include liquidinjection, PRP gel and bonding with bio-scaffolds. Obviously, withliquid injection, the required mechanical environment of cartilageformation is difficult to achieve; moreover, implanted scaffoldsmayincur unexpected risk and lack integration. The roles for therespective treatment regimens still need to be defined, becausemany of the questions concerning PRP mechanisms of actionremain unanswered.

Future directions of PRP application in OA therapy mayconcentrate on seeking an appropriate and innocuous agent likeanti-VEGF antibody that can modulate and control the effect of PRPby biological integration, when blocking VEGF, defects wererepaired mostly with hyaline cartilage57.

Author contributions

All authors were involved in drafting the article, and all authorsapproved the final version to be published.

Financial supportThis work is supported by National Natural Science Foundation ofChina (General Program), 81071457, National Natural ScienceFoundation of China, 31240047, National High Technology Researchand Development Program of China, 2011, National Natural ScienceFoundation of China (Key Program), 30930091, People’s LiberationArmy 12th five-year plan period (Key Program), BWS11J025, TheNational Basic Research Program of China (973 Program), 2011.

Competing interestsThe authors declare no competing interests.

References

1. Flanigan DC, Harris JD, Trinh TQ, Siston RA, Brophy RH. Prev-alence of chondral defects in athletes’ kneesda systematicreview. Med Sci Sports Exerc 2010;42:1795e801.

2. Erggelet C, Kreuz PC, Mrosek EH. Autologous chondrocyteimplantation versus ACI using 3Dbioresorbable graft for thetreatment of large full-thickness cartilage lesions of the knee.Arch Orthop Trauma Surg 2009:1e8.

3. Jones EA, Kinsey SE, English A, Jones RA, Straszynski L,Meredith DM, et al. Isolation and characterization of bone

Table IVDual character of PRP use for cartilage repair and OA in clinical

The strong facts for the useof PRP in clinical

The poor support for the useof PRP in clinical

Improve WOMAC, AOFAS andVAS scores.

Increased type I collagen whichnot exist in hyaline cartilage.

Symptomatic relief in early OA andimprove clinical outcome85.

Produce fibrous cartilage.

Inflammation reduction. Stimulates angiogenesis86


891892893894895896897898899900901902903904905906907908909910911912913914915916917918919920921922923924925926927928929930931932933934935936937938939940941942943944945946947948949950951952953954955

956957958959960961962963964965966967968969970971972973974975976977978979980981982983984985986987988989990991992993994995996997998999

100010011002100310041005100610071008100910101011101210131014101510161017101810191020



Zhu et al. 2013 Review

Basic science and clinical application of platelet-rich plasmafor cartilage defects and osteoarthritis: a review

Q7 Y. Zhu, M. Yuan, H.Y. Meng, A.Y. Wang, Q.Y. Guo, Y. Wang, J. Peng*

Institute of Orthopedics, Chinese PLA General Hospital, Fuxing 28# Road, Beijing 100853, China

a r t i c l e i n f o

Article history:Received 12 June 2013Accepted 30 July 2013

Keywords:Platelet-rich plasmaCartilage defectsOsteoarthritis

s u m m a r y

Cartilage defects (CDs) and the most common joint disease, osteoarthritis (OA), are characterized bydegeneration of the articular cartilage that ultimately leads to joint destruction. Current treatmentstrategies are inadequate: none results in restoration of fully functional hyaline cartilage, for uncertainlong-term prognosis. Tissue engineering of cartilage with auto-cartilage cells or appropriate mesen-chymal stem cell (MSC)-derived cartilage cells is currently being investigated to search for new therapies.Platelet-rich plasma (PRP), an autologous source of factors obtained by centrifugation, possesses variousfunctions. For culture of MSCs and cartilage cells, it might be substituted for fetal bovine serum (FBS)with high efficiency and safety. It enhances the regeneration of cartilage cells when added to cartilagetissue engineering constructs for repairing CDs and as regenerative injection therapy for OA. But chal-lenges also remain. Some of the growth factors (GFs) present in PRP have negative effects on the OA joint.It is therefore unlikely that a mix of GFs some of which have negative effects in the OA joint, as present inPRP, will be of benefit in OA. Future directions of PRP application may concentrate on seeking anappropriate and innocuous agent like anti-VEGF antibody that can modulate and control the effect of PRP.

! 2013 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

Introduction

Articular cartilage damage is usually caused by sports injuries oraccidental trauma and aging. It regularly progresses tomore seriousjoint disorders such as osteoarthritis (OA), necrosis of subchondralbone tissue or arthritis. An estimated 15% of the world’s populationhave joint diseases; more than 39 million people in the EuropeanUnion andmore than 20million Americans have OA. By 2020, thesenumbers will probably be doubled1.

After traumatic or pathological injury, hyaline articular cartilage,the load-bearing tissue of joint, has limited or no intrinsic capacityfor repair capacity, and even minor lesions or injuries may lead toprogressive damage and joint degeneration.

OA is a chronic degenerative joint disease characterized byprogressive destruction of articular cartilage, thinning and eventual

wearing of articular cartilage, thus resulting in painful, limited jointmovement. The degeneration of articular cartilage, mainly due tochanges in the activity of chondrocytes in favor of catabolic activity,which also involves other joint tissues, as alterations of themeniscus, sclerosis and edema in the underlying subchondral boneas well as intermittent inflammation of synovium.

Current treatments for articular cartilage damage, such as sur-gical intervention (microfracture, osteochondral auto- or allo-grafts), to repair articular cartilage are less than satisfactory andrarely restore full function. To obtain sufficient chondrocytes fortherapy, the required in vitro expansion usually induces cartilagecell dedifferentiation. Tissue engineering-based cartilage repair hasbeen pursued to provide more functional biological tissue. Thechondrocytes are taken from non-weight-bearing parts of intactjoint areas and expanded in cell culture, then transplanted into thedefective areas of the affected joints. Clinical trials of autologouschondrocyte implantation (ACI) have shown promise2.

Multipotent adult mesenchymal stem cells (MSCs) can differ-entiate into cells of the chondrogenic lineage and are isolated froma wide variety of tissue sources; they are easy to isolate withoutsignificant donor-site morbidity and are easier to expand in vitrothan chondrocytes3. These cells are also used for cartilage tissueengineering and chronic degenerative disorders and to preventcartilage degradation in OA because of their trophic/regenerative

Abbreviations: ATP, adenosine triphosphate; EGF, epidermal growth factor; KGF,keratinocyte growth factor; L-PRP, leukocyte-rich platelet-rich plasmaQ1Q2

* Address correspondence and reprint requests to: J. Peng, Institute of Orthope-dics, Chinese PLA General Hospital, Fuxing 28# Road, Beijing, China.Tel: 86 13910060749.

E-mail addresses: [email protected], [email protected] (J. Peng).

1063-4584/$ e see front matter ! 2013 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.http://dx.doi.org/10.1016/j.joca.2013.07.017

Osteoarthritis and Cartilage xxx (2013) 1e11

12345678910111213141516171819202122232425262728293031323334353637383940414243444546474849505152535455

5657585960616263646566676869707172737475767778798081828384858687888990919293949596979899

100101102103104105106107108109110



Eigene Anwendung

Illustriert E.Heuter

Pat < 50 Jahre 2-3 ACP – 1x Woche

D O C O R T H O




Rheumatology (Oxford). 2012 Jan;51(1):144-50. Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip. Sánchez M, Guadilla J, Fiz N, Andia I. Source Departamento de Investigación, Osakidetza, Basque Health Service, B° Arteaga 107, 48170 Zamudio, Vizcaya. Abstract OBJECTIVE: To assess the safety and symptomatic changes of IA injections of platelet-rich plasma (PRP) in patients with OA of the hip. METHODS: Forty patients affected by monolateral severe hip OA were included in the study. Each joint received three IA injections of PRP, which were administered once a week. The primary end point was meaningful pain relief, which was described as a reduction in pain intensity of at least 30% from baseline levels as evaluated by the WOMAC subscale at 6-months post-treatment. The visual analogue scale (VAS) and Harris hip score subscale for pain were used to verify the results. Secondary end points included changes in the level of disability of at least 30% and the percentage of positive responders, i.e. the number of patients that achieved a >30% reduction in pain and disability. RESULTS: Statistically significant reductions in VAS, WOMAC and Harris hip subscores for pain and function were reported at 7 weeks and 6 months (P < 0.05). Twenty-three (57.5%) patients reported a clinically relevant reduction of pain (45%, range 30-71%) as assessed by the WOMAC subscale. Sixteen (40%) of these patients were classified as excellent responders who showed an early pain reduction at 6-7 weeks, which was sustained at 6 months, and a parallel reduction of disability. Side effects were negligible and were limited to a sensation of heaviness in the injection site. CONCLUSIONS: This preliminary non-controlled prospective study supported the safety, tolerability and efficacy of PRP injections for pain relief and improved function in a limited number of patients with OA of the hip.

Cortison vs. PRP

Wir müssen Sie kennen und verstehen

D O C O R T H O


Intraartikuläre Knorpeltherapie Cortison bis PRP (ACP) O ... · Intraartikuläre Knorpeltherapie...

Documents

Transcript of Intraartikuläre Knorpeltherapie Cortison bis PRP (ACP) O ... · Intraartikuläre Knorpeltherapie...