Lattermann - Cartilage - Cartilage handouts.pdf5/12/2014 1 Clinical Treatment Algorithms and Decision Making for Cartilage Repair Christian Lattermann, MD Associate Professor for Orthopaedics

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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



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



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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)



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



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)



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



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



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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



PRODUCTS THAT ARE ON THE MARKET ANDHOW THEY ADD TO OR EXPAND THE OPTIONS?

Innovation

Clinical data

Looking at the outcomes…



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



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



www.sshs57.com

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WORKMAN’S COMP: ACI (20% REDUCTION IN

OUTCOME)



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



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)



Dr. Steven Cohen, Rothman Institute

Novel “out of the box” concepts:

“hammock”

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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



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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



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



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!!!



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



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



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ACTIVITY LEVEL: ACI



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



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



Myspaceantics.com

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What about the other 95% of the road to recovery?



•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?



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Central Problem:



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



ACKNOWLEDGEMENTS

Jennifer, Howard, PhD,ATC

Carl G. Mattacola, PhD, ATC Janey D. Whalen, PhD

Documents

Lattermann - Cartilage - Cartilage handouts.pdf5/12/2014 1 Clinical Treatment Algorithms and Decision Making for Cartilage Repair Christian Lattermann, MD Associate Professor for Orthopaedics