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Clinical Treatment Algorithms and Decision Making for Cartilage Repair
Christian Lattermann, MDAssociate Professor for Orthopaedics and Sports Medicine
Vice Chair for Orthopaedic ResearchDirector: Center for Cartilage Repair and Restoration
University of KentuckyTeam Physician University of Kentucky
Team Physician Eastern Kentucky University
Center for Cartilage Repair and Restoration
University of Kentucky
DISCLOSURES Industry:
Genzyme: Consultant (payments to KMSF non for profit) Icartilage: Consultant $ 0 Ceterix: Consultant (payments to KMSF non for profit) Smith&Nephew : Institutional Support
Current Grant Support: NIH-NIAMS: 1K23AR060275-01A1 (2012-2017) Arthritis Foundation (2012-2014)
Editorial Board / Board Memberships: OJSM, Cartilage, The Knee, Journal of Sports Rehabilitation Board Member ICRS, Scientific Review Cmte. AF (Great Lakes Chapter)
Reviewer for Journals: AJSM,CORR,JKS, O&C, Orthopaedics, Tissue Engineering
Center for Cartilage Repair and Restoration
University of Kentucky
Incidence
136 surgeons over 4.3 years 31,516 arthroscopies 63% with Lesions (2.7/knee)
Grade III 41% Grade IV 20% Fracture 1.3% OCD .7%
IV: < 40 y.o. = 5% (1,729 cases)
Curl et al.; Arthroscopy, 1997
Center for Cartilage Repair and Restoration
University of Kentucky
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Natural History 31 patients F/U: 14 years > 50% developed symptomatic joint
space narrowing
>25,000 scopes 60% chondral lesions 67% FCD’s, 2%OCD’s,29% OA lesions
1,000 patients (age39 + 14) 58% MFC, 9% LFC,6% trochlea
ACL injuries have a high (84-100%) rate of chondral injuries of varying severity.
Nishimori et al. KSSTA 2008, Frobell et al. JBJS 2011, Potter et al. AJSM 2012,
Mesner & Maletius, Acta Orthop Scand, 1996Center for Cartilage Repair
and RestorationUniversity of Kentucky
Widuchowski, the Knee 2007
Hjelle Arthroscopy 2002
ARE ARTICULAR CARTILAGE LESIONS AND MENISCUS TEARS PREDICTIVE OF IKDC, KOOS, ANDMARX ACTIVITY LEVEL OUTCOMES IN ACL RECONSTRUCTION? A 6‐YEAR MOON COHORTCOX ET AL. IN REVIEW AJSM 2013
Table 1. Significant Predictors of Each Outcome Scale at 6 Years (p values)
Structure IKDCKOOS
MarxSymptoms Pain ADL Sports/Rec QOL
Meniscus
Medial 0.003 0.001 0.001 0.004 0.025
Lateral 0.027 0.001 0.002 0.001 0.001 0.024
Articular Cartilage
MFC 0.012 0.017 0.002 0.05
LFC 0.002 0.029
MTP 0.002 0.033 0.024 0.02 0.029
LTP 0.037
Patella
Trochlea 0.031
Cohort f/u = 93% (1411/1512)
UK ACL DATA:
0
100
200
300
400
500
600
700
800
900
0-14 15-24 25-34 35-44 45-54 55+
1493 ACLR 2008-2012
ACL R
0
100
200
300
400
500
600
700
800
0-14 15-24 25-34 35-44 45-54 55+
ACLR KY 09
ACLRKY 10
ACLRKY 11
15% increase
ACLR performed in KY 2009-2011
The young patients (under 20) make up the majority of ACL replacement patients
Particularly concerning is that over 60% get diagnosed after 3months or longer
In the state of KY the age group under 25 has seen a 15% increase in ACL reconstructions performed between 2009 and 2011
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IMAGING:
Modalities: Plain x-rays (bilat):
a/p + lateral p/a flex weightbearing PF sunrise / merchant Long leg alignment
MRI: T1+T2+PD Sag,Cor,Ax Cartilage specific: DESS, FSPD etc Cartilage Quantifying: DGEMRIC, T1rho, T2 mapping,
Na+ scanning
Bone Scan: Whole body, three-phase
CT: PF alignment contrast (intra-articular)
Center for Cartilage Repair and Restoration
University of Kentucky
BIMC.org
SCOPE: Part of the pre-operative workup:
Lesion location / size “Character of the compartment” Unexpected findings: Technique choice
Caveat: do not rely on outside pictures only
Center for Cartilage Repair and Restoration
University of Kentucky
ICRS Grading Scale ©
ICRS Grade 3 – severely abnormalCartilage defects extending down >50% of cartilage depth (A) as well as down to calcified layer (B) and down to but not through the subchondral bone (C). Blisters are included in the grade (D)
ICRS Grade 0 – normal
1A
1B
ICRS Grade 1 – nearly normalSuperficial lesions. Soft indentation (a) and/ or superficial cracks or fissures
ICRS Grade 2 – abnormalLesion extending down to <50% of cartilage depth
ICRS Grade 4 – severely abnormal
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Microfracture
OSTEOCHONDRAL AUTOGRAFT
(MOSAIC/ OATS)
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ARTICULAR CHONDROCYTE IMPLANTATION
(ACI)
periosteum
OSTEOCHONDRAL ALLOGRAFT
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OSTEOCHONDRAL ALLOGRAFT
• Concept: • stored allograft• particulated juvenile allograft
cartilage• Advantage:
• easy applicable• Easier to obtain than OC allograft• Marketed as off-the shelf but really
is not.
• Clinical data: • Bonner et al. JKS 2010• Farr et al. ICRS 2010• Thompkins M AOSSM 2012• Post market study temp. stopped in 2012• >4000 cases done to date (5.5 years)
Center for Cartilage Repair and Restoration
University of Kentucky
Denovo NT (Zimmer)
Microfracture A utologous C hondrocyte I mplantation
O steochondral A llograft T ransplantation
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FCD
Cell transplantation:Denovo NT (Zimmer)
Osteochondral grafting:
• Autograft: • MOSAIC• OATS
• Fresh OC Allograft
Marrow Stimulation:• Microfracture• Antegrade drilling
Cell transplantation:
ACI
Currently available Treatment Options for Focal Chondral Defects
= currently available with clinical data
= available with less than minimal data
Allograft:Chondrofix (Zimmer)
Marrow Stimulation:Nanofracture (Arthrosurface)BioCartilage (Arthrex)
Concept:• Biphasic allograft plug
(MMTG)
Advantage:• Off the shelf availability
• Indications potentially the salvage patient that requires bridging (50 year old with isolated defect)
Clinical data: • No published clinical data to
date• Post-market trial ongoing
Center for Cartilage Repair and Restoration
University of Kentucky
A. Gomoll, Op Tech Orthop 2013
Chondrofix (Zimmer):
BioCartilage (Arthrex)• Concept:
• point-of care• Micronized Cartilage Matrix and microfracture
• Advantage:• Off the shelf availability• Easy application and use (microfracture)• Cost (~$1,000) per defect
• Experimental data: • fibrin glue retains grafts in goats
Lewis PB et al JKS 2009• allograft particles will heal defect in baboons
Malinin et al ICRS 2009• increased repair tissue and improved MRI T2 mapping
score in horses Fortier et al. JBJS 2010
• Clinical data: • None to date• 1 month follow-up
Center for Cartilage Repair and Restoration
University of Kentucky
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• MACI:– Ease of application– Potential for arthroscopic procedure– Option for tibial defects
• DENOVO NT:– Availability– Ease of application– Potential for arthroscopic procedure– Option for tibial defects?
• BIOCARTILAGE:– Ease of application– Potential for arthroscopic procedure
• CHONDROFIX:– Availability– Ease of application– Potential for arthroscopic procedure
• SUBCHONDROPLASTY:– Addresses subchondral bony edema (bone bruise)– Potentially an option in early Osteoarthritis– Adjunct to chondral repair procedures
• CERULEAU Probe:– Novel concept to address early chondral changes– Possible adjunct treatment– Preventative?
• KINESPRING:– Early and established OA– Temporary unloading on way to TKA
Center for Cartilage Repair and Restoration
University of Kentucky
PRODUCTS THAT ARE ON THE MARKET ANDHOW THEY ADD TO OR EXPAND THE OPTIONS?
Innovation
Clinical data
Looking at the outcomes…
Center for Cartilage Repair and Restoration
University of Kentucky
Ideal Cartilage Patient “The real World”
young Any age up to 55
Small defect size (< 2cm2) Symptomatic defects are usually larger than 2cm2
Isolated defect > 65% have more than 1 defect
Condyle Often in trochlea or patella
BMI <30 Yeah right…
Comply with Rehab Unlikely at best
6/137 patients in a cartilage practice would have been enrollable as per clinical trial criteria
High level clinical trial data guides our practice but reality often looks different.
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Date of download: 3/25/2012
Copyright © The Journal of Bone & Joint Surgery, Inc. All rights reserved.
From: A Randomized Trial Comparing Autologous Chondrocyte Implantation with Microfracture: Findings at Five Years
The Journal of Bone and Joint Surgery (American) 2007; 89:2105-2112 doi: 10.2106/JBJS.G.00003
Lattermann
Knutsen
MDC for Lysholm : ~13
DOES LOCATION HAVE AN EFFECT? Location:
Microfracture: Femoral condyles:
No: Mithoefer et al. AJSM 2006, 2009 Yes, central weight bearing portion of MFC:
Kreuz et al. OC 2006
Trochlea: worse results than condyles
Cell based techniques: Femoral condyles and trochlea
have similar results
Osteochondral allografts: Only small case series but primarily indicated for
large defects in condyles
OC autograft / Mosaic: Smaller size defects only, >80 successful in TF joint,
~70% in PF joint Hangody et al. JBJS 2003, Nho 2010
Donor site issues
Center for Cartilage Repair and Restoration
University of Kentucky
What about WC?
WC: negative predictor for outcome: 68% vs. 83% in ACI
McNickle et al. AJSM 2009
40% failure rate in WCpatients over 40
Rosenberger et al. AJSM 2008
OC allografts worse results when WCGazahvi et al. JBJS 1997
Large effect for WC: cannot be recommended as treatment if
patient goes back to heavy physical labor work
Lattermann et al. unpublished data
Center for Cartilage Repair and Restoration
University of Kentucky
www.sshs57.com
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WORKMAN’S COMP: ACI (20% REDUCTION IN
OUTCOME)
Center for Cartilage Repair and Restoration
University of Kentucky
Major effect!
(P<.001)
DO PREVIOUS PROCEDURES HAVE AN EFFECT?
Previous procedures: Re-MF: high failure rate
Mithoefer et al. AJSM 2009DeWindt et al. KSSTA 2011
increased failure rate for cell based procedures MF: 20% Abrasion arthroplasty: 27% Drilling: 28%
Rosenberger et al. AJSM 2009
N/A for OC allo/ auto graft (area removed)
Unknown for Chondral allografts
Center for Cartilage Repair and Restoration
University of Kentucky
www.sshs57.com
Subchondroplasty:
Concept: • chronic subchondral bone
bruises may represent chronic insufficiency fractures
• Injection of calcium phosphate with a guide under arthroscopy
Clinical data: • Small case series (60 patients
with 11 that progressed towards TKA)Cohen S et al. Tech Knee Surg 2012Sharkey PF et al. Am J Orthop
2012Cohen et al. Op Tech Orthop 2013
Clinical Trials.gov:• Cohort study (n=70) safety trial• (>20 points improvement in
KOOS pain)
Center for Cartilage Repair and Restoration
University of Kentucky
Dr. Steven Cohen, Rothman Institute
Novel “out of the box” concepts:
“hammock”
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Center for Cartilage Repair and Restoration
University of Kentucky
Subchondroplasty:
• 42 year old patient 3 ½ yrs after ACI MFC• ACI healed• Doing well but continues with medial sided pain
It may be a matter of size:
2cm2 is considered the clinically relevant sizebased upon empiric and experimental data(1.6cm2 (lateral) and 1.9cm2 (medial) Flanigan DC et al. Arthroscopy 2010)
25mm plugs
Condyle width 45mm Condyle width 29mm
DOES SIZE HAVE AN EFFECT? Size:
Negative predictor for Microfracture <4cm2 non-athletes, 2cm2 athletes
Mithoefer et al. AJSM 2006, 2009
No effect for cell based techniques:Beris et al AJSM 2011; deWindt et al KSSTA 2011;Ossendorf et al Sports Med Arthrosc Rehabil Ther Technol 2011; Rosenberger et al. AJSM 2008; McNickle et al. AJSM 2009; Knutsen et al. JBJS 2004;
Osteochondral allografts:Only small case series but indicated for large defects in OCD lesions and AVN/Osteonecrosis; Görtz et al. CORR 2010Emerson AJSM ,2007Karataglis, Knee 2005
OC autograft / Mosaic: Larger sizes requiring more than 2 plugs increase failure
rate Donor site issues
Center for Cartilage Repair and Restoration
University of Kentucky
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DOES SIZE CORRELATE WITH OVERALL OUTCOME
Prospective patient registry
57 ACI patients (35±7 yrs., 21 males) , min 2 years f/u
Patient Reported Outcomes completed pre-op and 3, 6, 12, and annually IKDC WOMAC Lysholm
Average follow-up 2 ±1 yrs.
Raw defect size correlations (p<0.05) Preoperative: WOMAC, r = 0.41 Postoperative: Lysholm, r = -0.30; WOMAC, r = 0.33
Relative defect size correlations (p<0.05) Preoperative IKDC, r = -0.31; WOMAC, r = 0.431 Postoperative IKDC, r = -0.29; Lysholm, r = -0.35;
WOMAC, r = 0.33
Center for Cartilage Repair and Restoration
University of Kentucky
Patients will improve regardless of their pre-operative score
The pre-operative score, however, determines the post-operative score
• IKDC of <36
• .57 sensitivity and 0.83 specific for identifying those with poor ( not meaningfully improved) outcome
• 72% Diagnostic Accuracy
• Relative risk of poor outcome is:ODDS: 2.54 ICC: 1.39 to 4.12
Center for Cartilage Repair and Restoration
University of Kentucky
Lower preop function scores associated with poorer outcomes:
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• Length of symptoms has an effect on the outcome of cartilage procedures. (VanLaue et al. AJSM 2011 (cell based) Ollat D et al. Orthop Traumatol Surg Res 2011(MOSAIC) )
the earlier we identify these individuals, the better the outcome will be.
Need for better diagnostics!!!
Center for Cartilage Repair and Restoration
University of Kentucky
UPDATE ARTICULAR CARTILAGE TREATMENT:WHAT CHANGED MY PRACTICE:
DOES ACTIVITY LEVEL HAVE AN EFFECT?
Microfracture: Defects < 2cm2: “work horse” (?)
Good short term results
2- 4cm2:: “option” ? 71% in NFL players RTP >4 seasons results deteriorate after 2-3 years < than 52% of high level athletes
make it back to prev. level 59% of all athletes make it back 50% NFL players make it back
Mithoefer et al. AJSM 2006,2009
Steadman et al. Jknee Surg 2003Harrison et al.Arthrosocpy 2010
Center for Cartilage Repair and Restoration
University of Kentucky
ACTIVITY LEVEL:
ACI: Age and high level Soccer:
<19 >90% RTP < 25 71% RTP > 25 29% RTP
Mithoefer et al. AJSM 2005
Sports activity (>1 time per week) improves outcome after ACI
Kreuz et al. AJSM 2007
Patient are more responsive to treatment if they participate in sports pre-operatively
Lattermann et al. unpublished data
Center for Cartilage Repair and Restoration
University of Kentucky
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ACTIVITY LEVEL: ACI
Center for Cartilage Repair and Restoration
University of Kentucky
Patients participating in sports are more responsive to treatment but:
Pietschmann et al. ICRS 2013:“resumption of high impact sports will lead to reduction in clinical outcomes”
Womac Lysholm IKDC
What about weight?
BMI 30-35 (obese): negative predictor for MF
Mithoefer et al. AJSM 2009
No effect on ACI patients McNickle et al. AJSM 2009,Zaslav et al. AJSM 2009
BMI inversely correlated to post-op PRO scoresLattermann et al, unpublished data
Center for Cartilage Repair and Restoration
University of Kentucky
www.sshs57.com
DOES AGE HAVE AN EFFECT? Age:
Negative predictor for MicrofractureMithoefer et al. AJSM 2006, 2009Kreuz et al. Arthroscopy, 2006Gobbi et al. KSSTA 2005
Unclear for cell based techniques: No effect: Rosenberger et al. AJSM 2008 Maybe: McNickle et al. AJSM 2009 Yes: Knutsen et al. JBJS 2004
Yes in patients with unicompartmental OA and concomitant HTOWood et al. Knee 2011
Basic Science: decreased synthetic ability of chondrocytes with increasing donor age
Age does not seem to have a significant correlation with outcome in patients <50 yearsLattermann et al. unpublished data
Center for Cartilage Repair and Restoration
University of Kentucky
Myspaceantics.com
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What about the other 95% of the road to recovery?
Center for Cartilage Repair and Restoration
University of Kentucky
•SIGNIFICANT DEFICITS IN KNEE EXTENSIONSTRENGTH AMONG ALL PATIENTS AT 6 MONTHS ANDPERSISTING AMONG PATELLOFEMORAL PATIENTS AT 12 MONTHS
Eccentric Knee Extension Concentric Knee Extension
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Preop 6 mos 12 mos
% U
nin
vo
lved
Eccentric FC
Eccentric PF
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Preop 6 mos 12 mos
% U
nin
vo
lved
Concentric FC
Concentric PF
WHAT DO I FIND IMPORTANT
Alignment: Any malalignment of more than 1-2 degrees requires
a correction => increases magnitude of procedure Less in PF joint as almost all of those procedures
receive a TTT
Subchondral edema /bone loss on MRI: Large subchondral edema in a subacute or chronic
setting indicates weakened subchondral bone => cell based chondral repair alone may not be sufficient
Bone loss >7mm may need to be addressed either changing the algorithm or requiring more extensive procedure (sandwich ACI)
Meniscal pathology: Lateral meniscus
PEARLS for the Cartilage Guy: What is important:
Know your patient population: follow-up Manage expectations
Timeline: crutches, rehab Cost
Beware of patients who: Have a goal of return to high impact activities History of non-compliance Symptoms only with highest level activities Unrealistic time constraints “10/10 pain all the time” WC?
Center for Cartilage Repair and Restoration
University of Kentucky
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Central Problem:
Center for Cartilage Repair and Restoration
University of Kentucky
What have I learned?
• Specific indications for specific procedures are starting to emerge from the literature
No “one size fits all” strategy!
• Look at your patients using objective and subjective outcomes scores to determine your personal success with different techniques
• First order is : do no harm!clinical studies need to guide our decision making process
• New technologies will not develop without physician support of clinical trials
consider taking part in these trials
• Do not take “gospels” at face value, be inquisitive andchallenge the paradigm
Center for Cartilage Repair and Restoration
University of Kentucky
ACKNOWLEDGEMENTS
Jennifer, Howard, PhD,ATC
Carl G. Mattacola, PhD, ATC Janey D. Whalen, PhD