9/17/2016
Disclosures
Entity
Monitoring the Health of Articular Cartilage
through Dynamic Imaging and Biomarkers
Type
KNG Health Consulting
Consultant
Stryker
Consultant
North Carolina Orthopaedic Association
Executive Committee
Richard C Mather III MD MBA
Assistant Professor
Duke Orthopaedics
Duke Clinical Research Institute
Cartilage Injury and FAI
Current treatment options limited
Microfracture outcomes deteriorate
–(2yrs, 5yrs)
–Domb et al, AJSM 2015
–Fontana, BJJ, 2015
Cartilage Injury a major predictor of outcome
WHY IS IT VALUABLE TO MONITOR THE
HEALTH OF ARTICULAR CARTILAGE?
Important to Patients
It is my son’s senior
season, can he play
through this pain?
When can I run again doc?
Can I run again?
Soccer, dancing, hockey?
I can live with this
pain right now, but
what is going to
happen with my
hip in the future?
My postop hip feels
great but I am starting
to have pain in my
other side – what
should I do?
Spectrum of FAI Syndrome
Asymptomatic?
Asymptomatic
Silent
Symptomatic?
FAI Syndrome
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Goal: understand articular cartilage health
Evaluate Interventions
Dynamic Imaging
Biomarkers
Mechanical Stress
Biologic Stress
Patient reported outcomes are not sensitive enough
Other outcomes can be confounded and non-specific
Current Models
DYNAMIC IMAGING
• Finite element
• Dual planar
fluoroscopy/CT
• Simulated ROM
• Estimation of soft
tissue involvement
3D Joint Models
Dynamic Imaging Opportunities
Dual planar fluorosocopy + MRI
1Van de
Velde, 2009
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Evaluate surgical approaches
Measuring In Vivo
Knee Motion
Example: ACL Graft Placement
Transtibial reconstruction often leads to a graft orientation that
does not restore force vector of the native ACL
Abebe 2011
Anatomic placement
Evaluate surgical approaches
Anteroproximal Placement
Stress Test of the Knee
After Exercise
Before Exercise
Lad, DeFrate et al, ORS, 2014
Eziamaka et al, J Biomechanics, 2013
Application to FAI
• Current activity
– Pilot funding to start building the model
– Heavily dependent on tracing manpower
• Questions to answer
1.
Insight to understanding asymptomatic FAI morphology,
silent disease and FAI syndrome
Impact of capsular and labral integrity on cartilage strain
Identifying activities and motions that create the most
cartilage strain
2.
3.
•
BIOMARKERS
CAM, pincer, dysplasia patterns
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Promise of Biomarkers
• Predictive beyond current capabilities
• Supports personalized medicine
• Foundation of work to build on
– Heart
– Knee
High Cytokines and Low Glycosaminoglycans in Synovial Fluid
6 weeks After ACL Tear Identify Group with Poor Prognosis
Hip is not necessarily analogous to knee…
Lesser repair response in hip OA vs knee
Chondrocytes
Knee: anabolic, high turnover state
Hip: quiescent
Hip: quiescent
Study Design – IA Steroids for Acute ACL Tear
Lateral Tibia T1ρ (ms)
40
High Inflammation
Cluster
35
30
Cluster 1
Cluster 2
25
BL
6M
1Y
T1ρ
Lateral Tibia
T2
Medial Femur
Lateral Tibia
Trochlea
Low Inflammation
Cluster
IL-10
2Y
IL-6
IL-8
High
Inflammation
Cluster
TNF-α
MMP1
Low
Inflammation
Cluster
MMP3
sGAG
(proteoglycan)
Amano K, Stabler R, Kraus V, Li X, Ma C. Correlating biochemical changes of synovial fluids with cartilage
T1ρ after ACL injury. Osteoarthritis & Cartilage 2016;24(April S60-61):87
C Lattermann (U Ky), K Spindler (Cleveland Clinic), V Kraus (Duke University)
Funded by the Arthritis Foundation
IA Steroids After ACL Tear Prevent Type II Collagen Degradation
3.5
CTX-II(ng/ml) = breakdown of collagen in articularpcartilage
< 0.011
p < 0.018
3
Control
Kenalog/Saline
2.5
2
Saline / Kenalog
n.s.
Kenalog/Kenalog
n.s.
n.s.
1.5
1
0.5
An Investigation into Potential
Biomarkers for Richard
Osteoarthritis
C. Mather III MD MBA
Progression in the Hip
0
me 0
2wks
surgery
Any intra-articular steroid (Kenalog) within 4-14 days after injury blocked collagen breakdown
C Lattermann (U Ky), K Spindler (Cleveland Clinic), V Kraus (Duke University)
Funded by the Arthritis Foundation
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9/17/2016
Synovial Fluid Analysis
Results
• Feasibility pilot study:
– Synovial fluid extracted from
91% (74/81) of patients
– 22 samples underwent
analysis with Meso Scale
Discovery V-Plex kits
– 40 analytes were analyzed
– The figure shows excellent
coefficient of variation
percentages (CV%)
• Pilot data demonstrates a reproducible protocol capable of
producing reliable biomarker data from patients with FAI
• No statistically significant correlation was obtained for age,
gender, or simple diagnostic data (i.e. no observed OA,
peripheral delamination, chondromalacia) from analytes
(p>0.05)
• The lack of correlation with gender or age is a welcome result
in that we hypothesize synovial fluid biomarkers will follow the
progression of OA and not patient demographic data
Identifying a biomarker footprint of the
progression of hip OA
Control
Prearthritic
Diagnosis
Radiographic Damage
End Stage OA
Peritrochanteric space
FAI/labral
Pathology
FAI with intra-operative
cartilage degeneration
Total Hip
Arthroplasty
Symptoms
Healthy Control
Prearthritic
Radiographic
Diagnosis
Damage
Degree of Cartilage Damage
End Stage OA
MRI
TSG-6 Analysis
•
TSG-6 is an HA binding protein
associated with inflammation
• The secreted protein
isassociated with OA
progression in the knee
• 91 patients, 3 year follow-up
with XR eval
• As a test to predict progression:
– Sensitivity = 91%
– Specificity = 82%
Biomarker Profile
Wiesiewski, et al, Osteoarthritis and Cartilage, 2014
TSG-6 Results in the Hip
• TSG-6 may also serve as
a biomarker of OA
progression in the hip
• TSG-6 mediated heavy
chain transfer activity:
– SF from OA knee joints:
31.3 ± 45.3 nM
– SF from FAI hip joints:
149.6673.73 nM
improving techniques
hip specific instruments
& implants
Poor healing potential
High value
Early Intervention
Biomarkers and imaging to
understand risk of progression
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9/17/2016
Thank you
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