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Subchondroplasty®
Procedure: Science,
Research and Clinical
Results Peter F. Sharkey, M.D.
Philadelphia, Pennsylvania
2
Entity Conflict
Zimmer Biomet Consulting, Royalties
Others:
ConvaTec Consulting
StelKast Royalties
PRN Stock, BOD
Corentec Consulting, Royalties
My Disclaimers
3
Disclaimer
Products represented in this presentation are in
process of obtaining CE mark. At this time, CE mark
is pending.
Background
4
5
• Osteoarthritis describes a “deteriorating” joint (cartilage, synovium,
ligaments, tendons and bone)
• OA affects 15% of world population1
• 20 Million with knee OA in North America2
• In people age 50 and over, 25% have pain in their knees on most days
and percentage is rapidly increasing 3
• OA complaints #1 reason for visits to physicians in US4
Clinical Situation
1. Miller, et al, Subchondroplasty of the ankle: A novel technique, doi 10.3827/faoj.2015.0801.0007
3. Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and
current use of primary health care. Ann Rheum Dis.2001;60:91–7. [PMC free article] [PubMed]
2. Arthritis Rheum, 1998 25: 125-33
4. Panush RS, Schmidt C, Caldwell JR, Edwards NL, Longley S, Yonker R, et al. Is running associated with
degenerative joint disease? JAMA. 1986;255(9):1152–1154.
Increasing Population of
Younger TKA Patients
•By 2016 > 50% of TKA pts will be younger
than age 651 in the US
•Fastest growth among pts 45-541
•By 2030 673% increase in patients who are
candidates for primary TKA (3.4 million)1
1. Kurtz et al, Projections of Primary Hip and Knee Arthroplasty in the United States
from 2005 to 2030. Journal of Bone and Joint Surgery. 2007
7
Current Treatment Options
• Non-surgical therapeutic methods (NSAID, injection,
bracing) have limited effectiveness for advanced OA
• Role of arthroscopy being questioned
• May help with mechanical symptoms
• Pain relief less predictable
• Osteotomy, UKA, TKA more effective, but more
invasive and not always predictable
• Complications common
• 1 in 6 patients “not satisfied” after TKA, without
obvious cause
Felson & Buckwalter, NEJM 2002
Moseley, et al, NEJM 2002
Kirkley et al., NEJM 2008
8
Clinical Situation
…AKA…
• Clinical picture radiographic evaluation
– patient 1: bone on bone but no pain
– patient 2: preservation of joint space, severe pain
≠
• Hallmark sign of OA is loss of cartilage
• Cartilage loss usually noted on plain radiographs
MRI has greatly expanded our knowledge
regarding OA
• MRI demonstrates:
- Bone damage and inflammation
- Non-bone causes of pain
(meniscal tear, synovitis, etc.)
• MRI reveals the primary reported source of
pain: subchondral bone marrow lesion
(BML)
9
MRI Changes the Picture
• “The presence or absence of joint space narrowing…was not significantly
associated with knee pain”
Hunter et al, Evolution of semi-quantitative whole joint assessment of
knee OA: MOAKS (MRI Osteoarthritis Knee Score). OA & Cartilage.
2011 Aug; 19(8) 990-1002
• Review of OA symptom predictors found that pain is:
‾ Strongly related to presence of a BML
‾ Moderately related to synovitis & effusion
‾ Weakly related to cartilage volume / thickness
Starr et al, Fundamental subchondral bone changes in
spontaneous knee osteoarthritis. Int J Biochem Cell Biol.
2005;37:224–236.
• Symptoms from BML occur due to irritation or disruption of sensory
nerves of bone marrow
10
BML: Main Source of Symptoms
Cicuttini et al, Association of pain with radiological changes in different compartments
and views of the knee joint. OA & Cartilage. 1996; 1063-4584(05)90232-1
BML Definition on MRI
• Region of bone demonstrating
hyper-intense marrow signal
• Recognized on fluid-sensitive,
fat-suppressed sequences
• Sometimes referred to as edema
due to recognition on fluid-
sensitive MRI sequences
12
Subchondral Bone
Primary function: shock absorption during joint loading
Subchondral bone = subchondral
bone plate + subarticular spongiosa
(supporting trabeculae)
Madry et al., 2010 The Subchondral Bone in
Articular Cartilage Repair: Current Problems in the
Surgical Management, Knee Surg Sports Trauma
tol Arthrosc 18(4) 434-447
13
Microcracks Lead to:
•Targeted remodeling and
removal of damaged tissue
•Stimulation of secondary
centers of ossification –Focal thickening of subchondral
plate
– Increased mineralization density in
some SC regions, but decreased in
others
– Increased vascularity
AC = Articular cartilage
CC = Calcified cartilage
Cr = Microcrack
OC = Osteochondral junction
Arrows = Osteoclasts
Concentration of Joint Forces
14
Bone Marrow Lesions (BML)
Different etiologies
Source of pain SUBCHONDRAL
STRESS FRACTURE
“REACTIVE” BME
Knee OA
• Articular cartilage: no pain fibers
• Synovium: some pain fibers; more
baroreceptors
• Ligaments: more proprioceptors
• Meniscus: Pain fibers only in vascular
(peripheral) zone
• Bone: pain fibers
15
Primary pain source?
Multifactorial;
Structural Correlates of Knee Pain
Dye, et al, Am J Sports Med. 1998
Marrow, mineralized bone and periosteum have rich sensory nerve supply
and sympathetic innervation
Periosteum has densest innervation, but subchondral bone has highest
volume of neural tissue
What Structures in Bone are Most
Innervated with Pain Fibers?
Mach DB, et al. Origins of skeletal pain: sensory and sympathetic innervation of the mouse
femur. Neuroscience. 2002;113:155–166.
Concentration of Joint Forces
• In a non-deteriorated, load is dispersed over a large area
• In a deteriorated joint, load is concentrated in small areas
• Focal loading causes damage in underlying subchondral bone
Diffuse force distribution Deteriorating Joint (load moved
peripherally) Madry et al., 2010
Bone Marrow Lesions and X-Ray
Progression on the Side of the Lesion
(Felson et al, A.I.M. 2003)
% of knees with
progression on side
of lesion
Adjusted OR
(95% CI)
Adjusted OR
including
malalignment
(95% CI)
MEDIAL
PROGRESSION
Medial BML 27/75 (36.1%) 4.7 (2.4,9.2) 3.3 (1.3,8.3)
No Medial BML 12/148 (8.1%) 1 1
LATERAL
PROGRESSION
Lateral BML 10/40 (25.0%) 7.4 (2.9,19.1) 3.7 (1.1,12.5)
No Lateral BML 10/183 (5.5%) 1 1
Histopathology of BML
• Minimal true edema
• Abnormal bone spicules with excessive
fibrosis, small areas of osteonecrosis
• Extensive bony remodeling with reversal lines
• Essentially the pattern often seen
after fatigue fractures in bone
20
Zanetti et al, Bone Marrow Edema Pattern in Osteoarthritic Knee: Correlation
Between MR Imaging and Histologic Findings, Radiol 2000; 215:835-840
Histopathology of BML
OA related BMLs represent a healing response to trauma such as
microtrabecular fractures of the subchondral bone.1
1 Eriksen EF, Ringe JD. Bone marrow lesions: a universal bone response to
injury? Rheumatol Int. 2012;32(3):575–584
High-mag histology image
showing subchondral fracture
Micro CT showing the bony
subchondral fractures
Histology of Bone Marrow Lesions
*Taljanovic et al, 2008
Histology of Bone Marrow Lesions
*Taljanovic et al, 2008
The Response to Microtrabecular
Fractures B
on
e S
tren
gth
Time
Remodeling Capacity Exceeded;
Cellular Recruitment
BML & Progression of Disease
BML Grade Odds Ratio of SBA
0 1.0
1 20.2
2 45.2
3 76.5
There was a strong association between prevalent BML
and SBA.
Felson et al, The Association of Bone Marrow Lesions with Pain in Knee
Osteoarthritis; Ann Intern Med. 2001 134 (7):541-9
The identification of BML is the strongest predictor of the presence of pain
associated with knee OA
o “Our results show that bone marrow lesions in knees are associated
with the most important symptom of osteoarthritis, pain.”
Roemer et al. Change in MRI-detected subchondral bone marrow lesions is
associated with cartilage loss: the MOST Study. A longitudinal multicentre
study of knee osteoarthritis. Ann Rheum Dis. 2009;68(9):1461–5.
BML correlate with OA disease progression
o “BML, which are a reflection of increased subchondral metabolism and
remodeling, might lead in some cases to alterations in the subchondral
osseous plate and eventually weakening and deformity.”
BML: Main Source of Symptoms
Scher, et al., Skeletal Radiology. 2008; 37: 609-17 • ~9x More likely to progress rapidly to TKR
Tanamas, et al., Rheumatology. 2010; 12: 2413-9 • Increased patient’s risk of TKR by 57%
Raynauld, et al., Ann Rheum Dis. 2011; 70: 1382-88 • Presence of medial BML is one of the strongest
predictors of TKR
Roemer, et al., Osteoarthritis and Cartilage. 2012;
20: 510-53 • Large medial BML are 2.5x and worsening medial BML
are 3.4x more likely for TKR
Patients with BML
Once a knee OA patient develops BML
without intervention TKA
• “Large bone marrow lesions in the medial femoral condyle or the medial or
lateral plateau were associated with substantially increased odds of
reported pain”
• BML in medial compartments associated with “marked decreases in
walking and stair-climbing performance (p<0.001)”
28
Patients with BML
Sowers et al. Associations of Anatomical Measures from MRI with Radiographically
Defined Knee Osteoarthritis Score, Pain, and Physical Functioning, JBJS Am.
2011;93:241-251
Jacobs CA, et al, Subchondral Bone Marrow Edema Had Greater Effect on
Postoperative Pain After Medial Unicompartmental Knee Arthroplasty Than
Total, J Arthroplasty. 2015, http://dx.doi.org/10.1016/j.arth.2015.09.023
• 71 patients with MRI taken before medial UKA or TKA
• Pain scores for UKA patients with BME were worse (before and after
surgery) than for TKA patients with BME
• Satisfaction rates were lower for UKA patients with BME
• BME did not effect satisfaction rates for TKA patients
Structurally compromised subchondral bone may not predictably support
UKA components
Patients with BML
Insufficiency fracture of tibial plateau may cause knee pain in osteoporotic patients.
BML found in 77.5% of persons with painful knees
Severity of BML associated with progression to TKR
Changes in bone play a role in development of knee pain
Poor clinical outcome after APM associated with bone marrow edema
BML
2010
2008
2001
2011
30
Clinical relevance of BML has been studied for >30 years
1983
BML Clinical Relevance
“Changes of subchondral bone are a classic feature of OA….characteristic
processes include microcracks..within the subchondral region.”
Kon E, et al. Bone marrow lesions and subchondral bone pathology of the
knee. European Society of Sports Traumatology, Knee Surgery,
Arthroscopy. 2016; 1797-814.
Summary
• Often a disconnect between clinical picture and plain
radiographic studies
• Presence of BML – highest predictor of clinical symptoms
• When BML are left untreated – progression to TKA likely
• Ideally, find an earlier, minimally-invasive treatment option for
BML defects to perhaps delay or avoid progressing to TKA
33
Minimally Invasive More Invasive
Po
ten
tia
l T
rea
tme
nt?
Treatment Options When
Conservative Care Fails?
34
Based on Accumulated Knowledge
Philosophical Solution: •Minimally-invasive procedure
•Biological stimulation of bone
• Access and fill bone marrow lesion
• Provide inorganic matrix for remodeling as bone heals
• Procedure that does not compromise bone for later TKA if needed
The Subchondroplasty®
Procedure
35
The Subchondroplasty Procedure
1. Preoperative plan, based on MRI
2. Target the BML—translate MRI to intraop fluoro
3. Access lesion with cannula
4. Inject AccuFill® bone substitute material
Preop Plan
• Localize BML relative to
radiographic anatomic
landmarks
• Fat-suppressed MRI (T2FS,
PDFS, STIR) in at least two
planes
• BML typically not visible on
fluoroscopy
38
Set Up
OR/Patient setup
for arthroscopy
and fluoroscopy
39
Target Bone Marrow Lesion
BML targeted with
fluoroscopy, based
on preop MRI
40
Drill Cannula
41
Inject AccuFill
42
AccuFill Bone Substitute
Material (BSM)
• Hardens in an endothermic reaction at 37°C no tissue necrosis
• Mixed with saline or blood to create injectable material
• Properties similar to the apatite of bone:
Ca10-x(M)x(PO4)6-x(HPO4,CO3)x(OH)2-x
• Macroporous: ~65% porosity, pore size ~300μm
• Compressive strength: ~10MPa, comparable to cancellous bone
• Cell-mediated remodeling as the body heals the defect
The Implant: AccuFill® Bone
Substitute Material (BSM)
Cohen, SB, Sharkey, PF. Subchondroplasty for
Treating Bone Marrow Lesions, Journal of Knee
Surgery, Dec. 2015.
Restrospective review of first 69 patients
46
Patient profile
• Chronic, aching pain (VAS ≥ 4/10)
• Failed conservative care
• Candidate for knee replacement
Clinical diagnosis of BML bone
defect could be in combination with
• Meniscal tear / extrusion
• Cartilage thinning / fraying / loss
• Mechanical symptoms / loose bodies
Surgical care
• 1 surgeon, 1 center
• SCP® procedure + arthroscopy
Retrospective Review of
1st 69 Consecutive Patients
General Study Protocol
46
Avg Min Max
Age 56 35 76
Length of Symptoms (months) 21.5 2 180
BMI 30.14 20.3 53.2
Treatment prior to SCP® Percentage
Cortisone 63% HA 73% NSAID 46% Scope 28% PMMx 28% PT 12% Bracing 21%
Cohen Clinical Series – 2008-2010
First 69 Patients—Demographics
Location Average Outerbridge Grade
Medial 3.34 Lateral 2.07 PF 2.53 Comp w BML 3.7 Contralateral Comp 1.8 Compartment Implicated Percentage MTP 46% MFC 40% LTP 10% LFC 4% Kissing 33%
Cohen Clinical Series –
Demographics/Baseline Data
• Patients chose SCP® Tx as alternative to TKA/UKA
• Regular follow up visits
• Data points collected
– VAS Pain
– IKDC
– Survivorship
Cohen Clinical Series –
Results
Patients followed ≥ 2 years
49
The majority of patients experienced clinically significant (>2 pt)
pain relief, including those that converted to TKA
Patients experienced durable pain relief beyond 2 years
Patients experienced durable improvement in IKDC
scores beyond 2 years
70% patients not converted to TKA at/beyond 2 years
In this series of 69 consecutive patients:
•Clinically-significant and durable improvements in pain
•Clinically-significant and durable improvements in function
•70% non-conversion to arthroplasty at minimum 2 years follow up
The SCP Procedure shows potential for patients with symptomatic
BML bone defects
Conclusions
54
55
Current Studies
The Evidence-Based
Approach in Bringing New
Orthopedic Devices to
Market (JBJS 2010)
Scientific & Clinical Basis For SCP Continues to Build
RCT
Cohort
Case Series
Case Reports
Biomechanics / Basic Science
Expert Opinion
Phase IV
Phase III
Phase II
Phase I
Evidence Pyramid
56
Current Studies
•Prospective Non-Randomized Knee Trial –5 sites (Rothman, Allegheny, Steadman-Hawkins Greenville,
CORE San Diego, NYU).
–Enrollment: 57 of 70; complete in 2016
–Includes 2 year controlled follow-up with MRI’s.
–1 year MRI publication 2017
–2 year Outcomes 2018
•Knee Observational Cohort Study (Registry) –Enrollment: 218 Subjects at 15 sites
•Academic sites and private practice
–All knee indications; represents real-world use of
SCP
–Goal: 1,000 subjects at 30 sites
–Submission in 2017
57
Current Studies
58
•201 Subjects; 2 Cohorts:
– Treatment: SCP + Arthroscopy
– Control: Arthroscopy + Sham
incision.
•2 year follow-up with Revision
and Pain Primary Endpoints
•Design Team/Initial Sites:
– Stanford (Dragoo, Vaughn)
– Steadman-Hawkins Carolinas
(Tokish, Wyland)
– Ohio State (Kaeding, Flanigan)
– Rothman (Cohen, Sharkey)
– Rush (Cole).
•Enrollment: 2016-2017
•10-15 Sites
•2 year F/U: 2019
•2 year publication: 2020.
Knee Randomized Controlled Trial
58
Pre-Clinical Study
59
60
40N impact to
both medial
femoral condyles
12 weeks 3 mos
Assess n=4 Clinical
Function
Pain
XR
MRI
Scope
microCT
Histo
Assess n=4 Clinical
Function
Pain
XR
MRI
Scope
microCT
Histo
6 mos
N=16
Assess n=4 Clinical
Function
Pain
XR
MRI
Scope
microCT
Histo
N= 7 on study
MRI, Scope & Treat
SCP
v
Sham
Assess n=3 Clinical
Function
Pain
XR
MRI
Scope
microCT
Histo
Study Design: James Cook, VMD
1-yr. Results Presented Tomorrow
Additional Clinical Publications
61
Knee Arthroplasty After Subchondroplasty: Early Results, Complications, and
Technical Challenges. Yoo JY1, O'Malley MJ1, Matsen Ko LJ1, Cohen SB1, Sharkey
PF1. J Arthroplasty. 2016 May 10. pii: S0883-5403(16)00018-8. doi: 10.1016/j.arth.2015.12.051.
[Epub ahead of print];
• 22 patients (15 TKA, 8 UKA) who had the Subchondroplasty Procedure, then subsequently
had knee arthorplasty
• SCP patients matched 2:1 to a control group of arthroplasty patients, who had no prior
surgery
• No difference in complications or surgical complexity between groups
Additional Publications
62
• MRI findings of subchondroplasty of the knee: a two-case report. Nevalainen M,
Sharkey P, Cohen S, Roedl J, Zoga A, Morrison B
Additional Publications
63
Discussion
64
Indications for Use:
• AccuFill Bone Substitute Material is an injectable, self-setting,
macroporous, osteoconductive, calcium phosphate bone graft substitute
material that is intended for use to fill bony voids or gaps of the skeletal
system of the extremities and the pelvis that are not intrinsic to the
stability of the bony structure. These defects may be surgically created
osseous defects or osseous defects created from traumatic injury to the
bone, including bone marrow lesions. AccuFill® Bone Substitute Material
is a bone graft substitute that resorbs and is replaced with new bone
during the healing process.
The Implant: AccuFill® BSM