A Longitudinal Outcomes Study of the Subchondroplasty® Procedure in the Foot/Ankle
Conditions: Insufficiency Fractures, Stress Fracture, Stress Fracture, Ankle, Foot and Toes
Sponsor: Zimmer Biomet

                                               
 
 
 
 
A Longitudinal Outcomes Study of the Subchondroplasty® Procedure in the 
Foot/Ankle  
Protocol No.: KC.CR.I.AM.16.2 
Version Date: January 04, 2017 
Version: 1.0 
 
Study Design: Multi-Center Uncontrolled Cohort (Clinical) Study 
 
 
 
 
 
STUDY SPONSOR:  
Zimmer Knee Creations, Inc.  
841 Springdale Drive 
Exton, PA 19341 
484-873-3343 
 
 
 
 
 
 
 
 
 
Confidentiality Statement: 
This document contains confidential information and is provided for the sole use of the Principal 
Investigator, Co-Investigators, Staff, Institutional Review Board or Independent Ethics 
Committee, and Regulatory Authorities.  By accepting this document, you agree to maintain the 
information as confidential and to use it only for the purpose of conducting the study. 

A Longitudinal Outcomes Study of the Subchondroplasty Procedure in the Foot/Ankle   
Protocol #: KC.CR.I.AM.16.2            version 1                                                            
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TABLE OF CONTENTS 
1.0 General Information _______________________________________________________ 4 
2.0 Protocol Signature Page ____________________________________________________ 5 
3.0 Protocol Synopsis __________________________________________________________ 6 
4.0 Abbreviations _____________________________________________________________ 8 
5.0 Introduction ______________________________________________________________ 9 
5.1 Clinical Background ____________________________________________________________ 9 
5.2 Product Description ___________________________________________________________ 10 
5.3 Preclinical Studies _____________________________________________________________ 10 
5.4 Case Studies__________________________________________________________________ 10 
5.5 Regulatory Overview of Subchondroplasty ________________________________________ 11 
6.  Risk Analysis _____________________________________________________________ 11 
6.1 
Risks of surgical intervention ________________________________________________ 11 
6.2 
Risks associated with subchondral implantation of AccuFill ______________________ 11 
6.3 
Methods to minimize risk ___________________________________________________ 12 
6.4  
Benefits and Justification for the Study________________________________________ 12 
7.0 Study Objectives __________________________________________________________ 12 
8.0 Study Design _____________________________________________________________ 12 
9.0 Subject Selection Criteria __________________________________________________ 13 
9.1 Inclusion Criteria _____________________________________________________________ 13 
9.2 Exclusion Criteria _____________________________________________________________ 13 
10.0 Study Procedures ________________________________________________________ 13 
10.1 Screening and Enrollment _____________________________________________________ 13 
10.2 Informed Consent ____________________________________________________________ 13 
10.3 Preoperative Procedures ______________________________________________________ 14 
10.4 Subchondroplasty Procedure __________________________________________________ 14 
10.5 Postoperative Procedures and Assessments _______________________________________ 15 
10.6 Evaluation Schedule __________________________________________________________ 15 
10.7 Telephone Interviews _________________________________________________________ 16 
Table 1.  Schedule of Events _______________________________________________________ 17 
11.0 Management of Intercurrent Events _________________________________________ 17 
11.1 Surgical Reoperation or Revision _______________________________________________ 17 
11.2 Postoperative Injections _______________________________________________________ 18 

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11.3 Missed Follow-up Completion of Questionnaires __________________________________ 18 
11.4 Protocol Amendments ________________________________________________________ 18 
11.5 Unscheduled Office Visits _____________________________________________________ 18 
11.6 Protocol Deviations and Violations ______________________________________________ 18 
11.7 Withdrawal and Study Re-Entry _______________________________________________ 19 
12.0 Adverse Event Reporting __________________________________________________ 20 
12.1 Relationship to study device or procedure ________________________________________ 20 
12.2 Adverse Event Data Collection _________________________________________________ 21 
12.3 Events Followed to Resolution __________________________________________________ 21 
12.4 Serious Adverse Events _______________________________________________________ 21 
13.0 Assessment of Safety _____________________________________________________ 22 
14.0 Statistical Considerations and Methodology ___________________________________ 22 
15.0 Data Management _______________________________________________________ 23 
15.1 
Data Collection ____________________________________________________________ 23 
15.2 
Data Submission __________________________________________________________ 23 
16.0 Records and Reporting____________________________________________________ 23 
16.1 
Disclosure of Health Information _____________________________________________ 23 
16.3 
Maintenance of Records ____________________________________________________ 24 
17.0 Materials and Supplies____________________________________________________ 24 
17.1 
Study Materials ___________________________________________________________ 24 
17.2 
Subchondroplasty Products _________________________________________________ 24 
18.0 Publication Policy _______________________________________________________ 24 
19.0 References _____________________________________________________________ 26 
Appendices _________________________________________________________________ 26 
Appendix A. Package Insert _______________________________________________________ 27 
Appendix B. Surgical Technique Guide ______________________________________________ 29 
Appendix C. Case Report Forms_______________________________________________51  
Appendix D. Informed Consent Form Template___________________________________84 
     
 
 
 

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Protocol #: KC.CR.I.AM.16.2            version 1                                                            
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1.0 General Information 
STUDY SPONSOR:  
Zimmer Knee Creations, Inc.  
841 Springdale Drive 
Exton, PA 19341 
 
ZIMMER STUDY REPRESENTATIVE 
 
Marianne Rahme, BA, CCRP 
Clinical Project Manager 
Zimmer Knee Creations, Inc.  
805 Springdale Drive 
Exton, PA 19341 
Tel: (484) 873-3343 
Fax: 484-879-4288 
E-mail address: Marianne.rahme@zimmerbiomet.com  
 
Patrick D. Reischling, MBS, CCRA 
Director, Clinical and Regulatory Affairs 
Zimmer Knee Creations, Inc.  
841 Springdale Drive 
Exton, PA 19341 
Tel: (720) 879-7828 
E-Mail address: Patrick.reischling@zimmerbiomet.com 
 
Monitor: 
iMARC Research Inc. 
22560 Lunn Road 
Strongsville, OH 44149 
Ph: 440-801-1540 
Fax: 440-801-1542 
 
Ethics Statement: 
The study will be performed in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with the ICH/Good Clinical Practice and applicable 
regulatory requirements. 
 
 
 

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Protocol #: KC.CR.I.AM.16.2            version 1                                                            
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2.0 Protocol Signature Page 
 
I have read and understand “A Longitudinal Outcomes Study of the Subchondroplasty® 
Procedure in the Foot/Ankle” and will conduct the study in accordance with all stipulations of 
the signed Clinical Trial Agreement (CTA), this protocol, including all attachments and 
amendments, and according to applicable Food and Drug Administration regulations, HIPAA, 
local regulations, ICH and GCP guidelines and the policies of the reviewing IRBs and 
institutions where the study will take place. 
 
Principal Investigator: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 (Print Name) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Signature) 
 
 
 
 
 
 
(Date) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Site Name) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Site Address) 
 
 

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3.0 Protocol Synopsis 
Sponsor/Company 
Zimmer Knee Creations, Inc. 
Study Title 
A Longitudinal Outcomes Study of the Subchondroplasty® Procedure 
in the Foot/Ankle  
Protocol Number 
KC.CR.I.AM.16.2 
Implant Material 
AccuFill® Bone Substitute Material 
Treatment  
Injection of a flowable calcium phosphate (CaP) synthetic bone-void 
filler into osseous defects in the bones of the Foot and/or Ankle 
(Subchondroplasty Procedure (SCP®)) as demonstrated by bone 
marrow lesions on diagnostic imaging. 
Number of Study Sites 
Up to 25 study sites 
Study Population 
Approximately 250 subjects, each with at least one bone marrow 
lesion (BML) in any of the bones of the foot and/or ankle who have 
elected to undergo or who have undergone the Subchondroplasty 
procedure, will be enrolled in the study.  
Study Design 
A post-market, multi-center, longitudinal, patient-reported outcomes 
study of a commercially available AccuFill bone substitute material 
used in the Subchondroplasty procedure of the foot and/or ankle. 
Study Objectives 
To collect data on the short- and long-term outcomes for subjects who 
are undergoing or who have undergone the Subchondroplasty 
procedure in the foot and/or ankle in a standard clinical setting. 
Outcomes to be assessed include medication usage, pain, function, 
health status and patient satisfaction. 
Inclusion/Exclusion 
Criteria 
Candidates must meet ALL of the following: 
1) Subject has at least one bone defect such as a BML, cyst or stress 
fracture confirmed by diagnostic imaging. 
2) Surgeon considers the patient appropriate for the SCP procedure. 
3) Subject provides voluntary signature on the IRB-approved 
Informed Consent. 
4) Subject is at least 18 years of age. 
5) Subject must be physically and mentally willing and able, in the 
Investigator’s opinion at the time of enrollment, to complete 
outcome forms via the internet, telephone, or regular mail. 
Candidates will be excluded if they meet ANY of the following:  

A Longitudinal Outcomes Study of the Subchondroplasty Procedure in the Foot/Ankle   
Protocol #: KC.CR.I.AM.16.2            version 1                                                            
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1) Subject is pregnant at the time of surgery. 
2) Subject is incarcerated. 
3) Subject is involved in active litigation related to the condition 
being treated. 
Pre-Operative 
Evaluations  
Initial study procedures include patient demographics, medical 
history, foot and ankle history, activity level, and each of the 
assessments and measures that will be applied longitudinally, 
including: 
• Use of pain medications 
• Subject-reported outcomes: 
o EQ-5D 
o Foot Function Index (FFI) 
o Numeric Pain Scale 
Study Procedure 
Each subject will undergo a Subchondroplasty® Procedure in at least 
one of the bones in the foot and/or in the ankle joint. 
 
Follow-Up 
• A numeric pain scale will be collected at the first post-
operative visit at approximately 2 weeks 
• Thereafter, subjects complete self-reported outcomes measures 
post-operatively at 6 weeks, 3 months, 6 months, 1 year and 2 
years via telephone, internet or mail. 
• Study coordinator will contact the subject by telephone at the 
above time points to inquire about any revision surgeries and 
adverse events.  
Telephone Interviews 
• Study coordinator will contact subject by telephone at 3, 4 and 
5 year time points to complete the numeric pain scale, global 
satisfaction survey and inquire about any revision surgeries. 
Post-Operative Subject 
Questionnaires 
• Use of pain medications 
• Subject-reported outcomes: 
o EQ-5D 
o Foot Function Index (FFI) 
o Numeric Pain Scale 
o Subject Global Satisfaction Survey 
Data Analysis 
Data collected in this study will be summarized descriptively and will 
be the basis of study reports.   
 
 

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4.0 Abbreviations 
AE 
Adverse Event 
BML 
Bone Marrow Lesion 
BMES 
Bone Marrow Edema Syndrome 
BSM 
Bone Substitute Material 
CaP 
Calcium Phosphate 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
EDC 
Electronic Data Capture 
ePRO 
Electronic Patient Reported Outcomes 
FDA 
Food and Drug Administration 
FFI 
Foot Function Index 
HIPAA 
Health Insurance Portability and Accountability Act 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
MRI 
Magnetic Resonance Image(ing) 
NSAID 
Non-steroidal Anti-inflammatory Drug 
OA 
Osteoarthritis 
SAE 
Serious Adverse Event 
SCP 
Subchondroplasty 
TKA 
Total Knee Arthroplasty 
USADE 
Unanticipated Serious Adverse Device Effect 
 
 
 

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5.0 Introduction 
5.1 Clinical Background  
Subchondral bone defects, sometimes called bone marrow lesions (BMLs), are MRI-visible 
defects that can be seen on fat-suppressed MRI sequences (T2FS, PDFS, etc.) where they appear 
as a hazy white area against the background of darker bone.  Pathologists have shown that BMLs 
represent a healing response to trauma such as micro trabecular fractures of the subchondral bone 
[1]. BML defects have been highly correlated with pain symptoms in the knee [2, 3]; however, 
BMLs and their effect on foot/ankle pain and function have not been as thoroughly studied 
clinically. Moreover, because the ankle joint differs from other joints in the lower extremity with 
unique anatomic, biomechanical and biologic characteristics [4], so too do foot/ankle BMLs 
differ in prevalence, clinical presentation and clinical course [5].   
Early articles in the radiographic literature are generally descriptive, characterizing the MR 
appearance of bone marrow lesions in the foot and ankle using a variety of pulse sequences. The 
etiology of these imaging features can sometimes be attributed to marrow abnormalities such as 
osteonecrosis, stress fracture, bone contusion, tumor, etc., [5, 6, 7, 8, 9] however not all bone 
marrow lesion patterns are as clear cut [5].  BMLs in the foot and ankle tend to involve multiple 
bones, are generally seen in younger patients and present with a clinical history of prolonged 
pain without a distinct history of prior trauma [5, 10, 11]. In a retrospective review of 72 patients 
whose MRIs of the foot demonstrated edema-like bone marrow abnormalities, Zanetti et al. 
concluded that edema-like patterns of unknown etiology are clinically relevant and predictors of 
long-lasting pain [10]. These findings were substantiated by Fernandez-Canton, et al. in a 
comparison of MRI imaging one year after the initial diagnosis of transient bone marrow edema 
syndrome (BMES) in 25 patients. Previously, BMES had been considered a benign disease that 
typically resolved in 3-12 months, but in this study, almost a third of the patients showed 
persistence of edema at one year with 8% showing no improvement, leading to the conclusion 
that patients experience pain for an extended period of time [8]. 
Treatment options for BMLs of the foot and/or ankle have been conservative in nature, including 
non-steroidal anti-inflammatory drugs, injections, calcium, physical therapy, extracorporeal 
shock therapy and activity modification [5, 8, 11]. Operative treatments can be joint sparing or 
joint destructive, however, considering the generally younger, physically active patient 
population with BMLs of the foot/ankle, a joint sparing procedure that does not preclude more 
extensive procedures in the future is desirable. Subchondroplasty® (SCP®) is a minimally-
invasive procedure first described in 2007 to fill subchondral osseous defects associated with 
bone marrow lesions using an injectable bone substitute material (BSM), AccuFill® [12]. 
AccuFill is an injectable, self-setting, macro-porous, osteo-conductive, calcium phosphate bone 
graft substitute material that is intended for use to fill bony voids or gaps of the skeletal system 
of the extremities, spine (i.e. posterolateral spine), 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. AccuFill is a bone graft substitute that 
resorbs and is replaced with new bone during the healing process. AccuFill has unique properties 
that allow it to flow through the osseous defects in trabecular bone and then set up hard at body 
temperature [13]. Two year results from a clinical study of the knee on 66 subjects considering 
total knee arthroplasty (TKA) has shown improvements in subject reported pain and function 

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with only 30% of subjects undergoing revision to TKA at 2 years [14]. The goal of this study is 
to track outcomes in a population undergoing SCP of the foot and/or ankle. 
5.2 Product Description 
The Subchondroplasty Procedure targets and fills bone defects with AccuFill BSM utilizing an 
arthroscopic / percutaneous approach as follows.  Preoperatively, the BML bone defect is 
identified on fat-suppressed MRI, and the approach and trajectory is planned based on defect 
location. Using intraoperative fluoroscopy, the bone defect is localized relative to MRI findings. 
The appropriate AccuPort® Delivery Cannula is drilled to the bone defect. AccuFill BSM is then 
injected into the subchondral bone defect. The AccuFill fills the edematous void and hardens 
within the BML, and is resorbed over time and replaced with new bone during the healing 
process. 
The Subchondroplasty procedure will be performed using two commercially available devices:  
AccuFill and SCP® Surgical Instrumentation.  
AccuFill is an injectable, self-setting, macro-porous, osteo-conductive, calcium phosphate bone 
graft substitute material that is intended for use to fill bony voids or gaps of the skeletal system 
of the extremities, spine (i.e. posterolateral spine), 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. AccuFill is a bone graft substitute that 
resorbs and is replaced with new bone during the healing process. 
The SCP® Surgical Instrumentation is a set of manual surgical instruments used to target and 
deliver AccuFill to the osseous defect. 
5.3 Preclinical Studies 
Preclinical studies in established animal models were used to evaluate safety and effectiveness of 
AccuFill for treatment of a critical sized bone defect. A rabbit bilateral lateral femoral condyle 
defect model (4.8 mm diameter x 6 mm length cylindrical defect) through 24 weeks 
demonstrated that AccuFill caused bone induction and osteointegration at the implant sites, and 
was well tolerated. 
No significant adverse events or indications of infections or rejections of the AccuFill material 
were observed in the preclinical evaluations of AccuFill.  Studies demonstrated bone induction, 
osteointegration and potential for use as a bone void filler. 
5.4 Case Studies 
 
Miller and Dunn reported on two case studies using the Subchondroplasty procedure in the 
ankle. The first patient presented with chronic ankle pain and instability after suffering a severe 
ankle sprain four years prior and who failed conservative management with corticosteroid 
intraarticular injections. An MRI revealed chronic tearing of the anterior talofibular ligament, 
anterior tibial joint spurring and a subchondral bone marrow lesion in the medial aspect of the 
talar dome. The second patient presented with continued ankle pain following a previously 

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nonoperatively treated fibular non-union. An MRI revealed a large osteochondral lesion in the 
anterior-lateral aspect of the talar dome, subchondral talar edema and a chronic tear of the 
anterior talofibular ligament. Both patients underwent the Subchondroplasty procedure in 
conjunction with a modified-Bröstrom procedure. Patient One also had an anterior ankle 
arthrotomy and Patient Two had juvenile articular cartilage allograft delivered to the defect. At 
the 10 month follow-up visit, Patient One reported mild discomfort while golfing, while Patient 
Two returned to full activities without restrictions. Both patients state they would elect to have 
their procedures performed again [11]. 
5.5 Regulatory Overview of Subchondroplasty 
This study will evaluate the on-label use of AccuFill during the Subchondroplasty procedure. 
The Subchondroplasty procedure will be performed using two commercially available devices. 
The regulatory status of each component of the system is described below: 
1. AccuFill® Injectable Calcium Phosphate – Class II device; 510(k) Number 
K093447 - Calcium Salt Bone Void Filler Device, cleared by FDA. The package 
insert provides product description, indications, and usage information. 
(Appendix A).   
 
2. SCP® Surgical Instrumentation – These are Class I manual surgical instruments. 
Per 21 CFR 888.4540, manual surgical instruments are premarket exempt. 
6.  Risk Analysis  
This study was designed to assure that the benefits and knowledge gained by studying clinical 
outcomes associated with Subchondroplasty for treatment of BMLs in the foot/ankle outweigh 
the potential risks to the subjects.  Alternative treatment options may require more invasive 
surgical therapy to treat the painful foot/ankle, up to and including arthrodesis or arthroplasty.  
6.1 
Risks of surgical intervention  
With any surgical procedure, there are risks of complication including those risks currently 
associated with surgical interventions in the foot/ankle. These risks include intra-articular 
adhesions (scar tissue), superficial and/or deep wound infection, nausea and/or vomiting, 
bleeding, ankle pain, muscle weakness, and postoperative blood clot (hematoma).  There are 
possibilities of wound re-opening, deep vein thrombosis (blood clot), pulmonary embolus (lung 
clot), vascular or nerve injury, and an allergic response to the anesthetic or medications.  Some 
additional risks related to local anesthesia are swelling, pain, bleeding, bruising, nerve pain and 
loss of sensation in the skin and ligament around the foot/ankle.   
6.2 
Risks associated with subchondral implantation of AccuFill  
Risks specific to the implantation of a bone marrow substitute may include tissue thinning over 
the implant site, tenderness/redness/edema, seroma/hematoma, infection, swelling/fluid 
collection and loss of contour. Migration, extrusion, dehiscence, fracture and sloughing of 
AccuFill can occur as a result of excessive trauma. Neurovascular injury may occur due to 

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surgical trauma.  A pulmonary embolism may result from using this injectable bone void filler. 
6.3 
Methods to minimize risk  
Only appropriate subjects, who meet the include inclusion and exclusion criteria, will be 
recruited into the study.   
Study subjects will be monitored post-operatively to assess the surgical site for any acute and 
chronic adverse reactions to ensure proper medical treatment can be administered. Validated and 
standardized outcome scales and surveys will be used to collect subjects’ data.  Experienced 
orthopedic or foot/ankle surgeons will participate as investigators and have experienced staff to 
perform the study procedures.  
6.4  
Benefits and Justification for the Study  
This is an observational study and there are no direct benefits to the subject, other than those 
associated with the treatment of a bone marrow lesion of the foot and/or ankle. The justification 
for this study is to learn more about patient outcomes following the Subchondroplasty procedure 
in the foot/ankle.  
7.0 Study Objectives  
The purpose of this post-market clinical study is to collect data on the short- and long-term 
outcomes for subjects who are undergoing or who have undergone the Subchondroplasty 
procedure in the foot and/or ankle in a standard clinical setting. Outcomes to be assessed include 
medication usage, pain, function, activity levels and patient satisfaction. 
8.0 Study Design 
This is a post-market, multicenter, prospective, patient outcomes centered study to evaluate the 
on-label use of AccuFill during the Subchondroplasty procedure. Enrolled subjects will satisfy 
the inclusion/exclusion criteria and have at least one BML in any of the bones of the foot and/or 
ankle joint. 
Demographics, medical history and medications will be recorded at the time of enrollment. 
Subjects will complete validated patient reported outcomes measures pre-operatively. Surgical 
details including the SCP® procedure, concomitant surgical procedures and intraoperative safety 
events will be recorded. Pain outcomes will be assessed at the first post-operative visit (7-21 
days).  Information on medication usage, pain, function, health status and subject global 
satisfaction will be collected post-operatively at approximately 6 weeks, 3 months, 6 months, 1 
year, and 2 years. Subject global satisfaction and numeric pain scores will be collected at 3 years, 
4 years and 5 years post-surgery.  Screening for adverse events and revision surgeries will occur 
throughout the study.  The target enrollment is 250 subjects. 
Subjects will complete the study at 5 years or will be withdrawn if the patient undergoes revision 
of the Subchondroplasty site. For the purposes of this protocol, a revision will be defined as any 
joint arthroplasty, fusion or any bone fixation, bone grafting or bone substitute procedure on the 
index foot/ankle. 

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9.0 Subject Selection Criteria  
9.1 Inclusion Criteria 
Candidates must meet ALL of the following: 
1) Subject has at least one bone defect such as a BML, cyst or stress fracture confirmed by 
diagnostic imaging. 
2) Surgeon considers the patient appropriate for the SCP procedure. 
3) Subject provides voluntary signature on the IRB approved Informed Consent Form. 
4) Subject is at least 18 years of age. 
5) Subject must be physically and mentally willing and able, in the Investigator’s opinion at the 
time of enrollment, to be compliant with the protocol and complete outcome forms via the 
internet, telephone or regular mail. 
9.2 Exclusion Criteria 
Candidates will be excluded if they meet ANY of the following:  
1) Subject is pregnant at the time of surgery. 
2) Subject is incarcerated. 
3) Subject is involved in active litigation related to the condition being treated. 
10.0 Study Procedures  
10.1 Screening and Enrollment 
Potential subjects will be screened from each investigator’s patient population to determine if 
they meet the inclusion criteria described in Section 9.1 and none of the exclusion criteria 
described in Section 9.2. Subjects will not be invited to participate in the study until after 
approval of the protocol by the reviewing IRB. Subjects will be considered enrolled in the study 
if they meet the inclusion/exclusion criteria, sign a consent form, and undergo the SCP 
procedure. With prior approval of the Sponsor, the site may enroll subjects who have previously 
undergone Subchondroplasty. The subject will sign informed consent prior to completing follow-
up study questionnaires. The Study Site will maintain a Subject Enrollment Log for all enrolled 
subjects. 
10.2 Informed Consent 
All study subjects are required to undergo the process of Informed Consent and sign an 
Institutional Review Board (IRB) approved Informed Consent Form, compliant with 21 CFR 
Part 50 - Protection of Human Subjects, and in accordance with institutional policies. The 
Informed Consent Form must be signed prior to the collection of any protocol-specific data. 
Two copies of the informed consent will be made and distributed as follows: (1) the original of 

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the signed informed consent will be kept in the subject’s file at the study site and (2) a copy will 
be provided to the subject. 
If the Study Site does not have an IRB of record, a central IRB may be utilized upon approval by 
Zimmer Knee Creations. 
10.3 Preoperative Procedures 
All preoperative procedures are to be completed prior to the study surgery. The Schedule of 
Events is listed in Table 1. 
10.3.1 The preoperative visit will include collection of basic demographic information, 
medical history, foot and ankle history and current use of prescription and over-the-
counter pain medication. 
10.3.2 The subject is to complete a series of surveys and scales regarding their clinical 
outcomes at the time preceding surgery, including pain, stiffness, function, and activities.  
These scales include: 
• The Foot Function Index (FFI) 
• EQ-5D 
• Numeric Pain Scale 
10.3.3 For subjects enrolled after the completion of the Subchondroplasty procedure, 
basic demographic information, medical history, foot and ankle history and pre-op use of 
prescription and over-the-counter pain medication data should be collected, if available, 
from the subject’s medical record. Pre-operative FFI, EQ-5D, and/or numeric pain scale 
should be entered if they were collected as part of the standard of care. 
10.4 Subchondroplasty Procedure 
All operative procedures are to be performed under aseptic conditions according to the 
institution’s standards and following the guidelines below. 
• The preoperative MRI should be used in planning the access point, trajectory and 
depth of the AccuPort cannula(s) for accessing the location of the BML(s).  
• AccuPorts should be placed using fluoroscopic guidance.   
• Use of the SCP Navigation guide is optional. 
• Appropriate volume of AccuFill should be used to adequately fill the area(s) of 
BML(s), per the surgical technique guide in Appendix B, taking care not to over-
pressurize or overfill the defect. Multiple fluoroscopic images should be taken during 
injection to check for extravasation of material.  
• Any extravasation of material into surrounding soft tissues should be thoroughly 
irrigated at the time of the procedure. 
The investigator is to dictate detailed operative notes that include the measures listed below, or 
have paper copies of the Surgical Documentation Case Report Forms completed during surgery 
to serve as source documents.  

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Surgical Documentation 
• OR time 
• SCP procedure time 
• Anesthesia type 
• Intraoperative adverse events 
• Documentation of SCP injection 
o Type of AccuPort(s) used (end target, side target, gauge, etc.) 
o Volume of AccuFill injected for each lesion 
• Lot numbers of SCP Complete Kit, AccuFill, AccuPort(s) and AccuMix used 
• Documentation of treated BML(s) 
• Concomitant procedures  
10.5 Postoperative Procedures and Assessments  
During the immediate postoperative period, the investigator’s standard postoperative care 
procedures should be followed. All adverse events and complications are to be assessed and 
recorded on the Adverse Event Form, per Section 11.0 Adverse Event Reporting. 
Rehabilitation should be performed per the investigator’s standard of care. 
10.6 Evaluation Schedule 
Patients will be enrolled at the physician’s office. A numeric pain score will be collected at the 
first post-operative standard of care visit at approximately 7-21 days. Subjects may complete 
follow-up questionnaires in the office, over the telephone, or online through an EDC system at 
the selected time points post-operatively at 6 weeks, 3 months, 6 months, 1 year and 2 years. At 
the 3, 4, and 5 year time points, the study coordinator will contact the subject by telephone to 
remind the subject to complete the numeric pain scale, the global satisfaction survey and record 
any revision surgeries. 
If internet access is not available, questionnaires may be mailed to study subjects by their study 
physician at the selected time points and mailed back to their study doctor. 
Follow-up evaluations are detailed in Table 1 Schedule of Events.  Follow-up is to occur within 
the windows described in Table 1. 
10.6.1 Any medications or therapies used for pain relief are to be recorded, specifically 
the classification (acupuncture, analgesic/non-narcotic, anti-inflammatory, narcotic, etc.), 
and whether or not the medication/therapy usage is related to the index foot/ankle.  Any 
hyaluronic acid or cortisone injections should be recorded.  
10.6.2 The subject is to complete a series of surveys and scales regarding their clinical 
outcomes during the time frame indicated on the form.  These scales include: 
• Foot Function Index (FFI) 
• EQ-5D 
• Numeric Pain Scale 
• Subject Global Satisfaction Survey 

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The study database will be configured to send an email notification to subjects at the 
beginning of each specified visit window with a reminder that they need to complete the 
surveys. This email will contain a method to allow the subjects to complete their surveys 
electronically via the database’s electronic subject reported outcomes (ePRO) system. 
Prior to conducting the study visit, the Study Coordinator will check to confirm whether 
these surveys have been completed electronically or not. If time is an issue, the Study 
Coordinator will fax, email or mail a copy of the surveys to the subject with instructions 
for completion or initiate another reminder from the ePRO system. Mailed surveys will 
be sent with a stamped, return envelope. The subject should be instructed to return the 
surveys within one week. Any subject survey forms that are not collected via the 
database’s ePRO system are to be maintained in the subjects’ study files as source 
documents.  
10.6.3 A Subject Stipend may be offered to the subject at the completion of each follow-
up time point, if in accordance with the institution’s policies.  
10.7 Telephone Interviews 
The Study Coordinator will schedule a call with the subject within the visit window. 
During the call, the subject is to be queried regarding the occurrence of any Adverse Events and 
Serious Adverse Events, per Section 12.0 Adverse Event Reporting.  Any adverse event that 
results in reoperation or revision is to be recorded as a Serious Adverse Event.   
The subject is to be queried regarding any reoperations of the index foot/ankle.  All reoperations 
are to be documented using the Surgical Reoperation Form, per Section 11.1. 
The subject will be reminded to complete the online surveys. The subject can also elect to 
complete the surveys via the telephone or  mail. Any subject survey forms that are not collected 
via the database’s ePRO system are to be maintained in the subjects’ study files as source 
documents. 
The Study Coordinator is to document the phone interview in the Telephone Log, including any 
completion of outcome measures via the phone. 
At the 3, 4 and 5 year follow-up, the Study Coordinator will inquire  about Adverse Events, 
Serious Adverse Events and reoperations, and remind the subject to complete the Global 
Satisfaction Survey and Numeric Pain Scale. 
 
 
 

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Table 1.  Schedule of Events 
 
Visit 1 
Visit 2 
Visit 3 
Post-Op 
Questionnaires 
Post-Op 
Questionnaires 
Post-Op 
Questionnaires 
Post-Op 
Telephone 
Call 
Procedures 
Study 
Admit/ 
Pre-
operative 
Operative 
SOC Post-
Op Visit 
(7-21 days) 
 
 
6 weeks 
 
 
3 months 
6 months 
1 year 
2 years 
3 years 
4 years 
5 years 
Visit Window 
≤60 days 
Prior to 
Surgery 
 
 
±7 Days 
±14 Days 
±60 Days 
±60 Days 
Informed Consent  
X 
 
 
 
 
 
 
Inclusion & Exclusion Criteria 
X 
 
 
 
 
 
 
Demographic Form 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Pain Medications/Therapies 
X 
 
 
P 
P 
P 
 
FFI 
P 
 
 
P 
P 
P 
 
Numeric Pain Scale  
P 
 
X 
P 
P 
P 
X 
EQ-5D 
P 
 
 
P 
P 
P 
 
Global Satisfaction Survey 
 
 
 
P 
P 
P 
X 
Surgical Documentation 
 
X 
 
 
 
 
 
Adverse Event or Serious 
Adverse Event2 
 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Protocol Deviation2 
 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Telephone Contact2 
 
 
 
X 
X 
X 
X 
Surgical Reoperation3 
 
 
(X) 
(X) 
(X) 
(X) 
(X) 
Study Exit4 
 
(X) 
(X) 
(X) 
(X) 
(X) 
X 
X  Investigator completed forms 
(X) Completed by Investigator when required 
P  Subject completed forms 
2 Case Report Forms to be completed if/when event occurs. 
3 Surgical Reoperation form will be completed if the investigator performs any procedure on the index foot/ankle  
  regardless of whether the subject’s change in condition is related to the initial study procedure. 
4 Study Exit form will be completed if the subject is no longer participating in the study for any reason. 
11.0 Management of Intercurrent Events   
11.1 Surgical Reoperation or Revision 
A reoperation of the index foot/ankle or revision SCP injection site may be performed at the 
discretion of the Investigator (e.g., due to progressive pain or disability, etc.).  A reoperation is 
defined as any surgical procedure on the index foot or ankle.  For the purposes of this protocol, a 
revision will be defined as any partial or total joint arthroplasty or any fusion, bone fixation, 
bone grafting, or bone substitute procedure in the study foot or ankle. 
The investigator is to dictate detailed operative notes that include the measures listed below, or 
have paper copies of the Surgical Reoperation Form completed during surgery to serve as a 
source document. 
11.1.1 
Surgical Reoperation Documentation 
• Reason for surgery 

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• Postoperative diagnosis 
• OR Time 
• Anesthesia Type 
• Status of the Subchondroplasty Injection Location 
 
If the reoperation occurs due to an adverse event, the event should be documented on a Serious 
Adverse Event Form and the surgery documented on the Surgical Reoperation Form.  
11.1.2 
In the event that a revision occurs (defined as any partial or total joint arthroplasty 
or any fusion, bone fixation, bone grafting, or bone substitute procedure in the index 
foot/ankle), the subject will be exited from the study. A Serious Adverse Event Form and 
Surgical Reoperation Form will be completed. 
11.1.3 
In the event that a reoperation occurs that does not involve revision of the BML 
site(s), a Serious Adverse Event Form and Surgical Reoperation Form will be completed, 
and the subject will continue to be followed in the study per protocol.  
11.2 Postoperative Injections 
Use of any postoperative injections into the index foot/ankle should be recorded on the 
Medication Form at the next questionnaire completion window. 
11.3 Missed Follow-up Completion of Questionnaires 
If a subject fails to complete the post-operative questionnaires at a follow-up time point, the site 
should continue to attempt follow-up of the subject through the five year study end point. The 
subject should only be exited from the study under the conditions described in section 11.7. 
11.4 Protocol Amendments 
Any proposed amendments to this protocol must be submitted in writing and pre-approved by the 
Sponsor. All Sponsor-initiated protocol amendments will be documented in writing, including 
the date and justification for the change, and communicated in a timely manner to the 
investigators.  All amendments are to be approved by the reviewing IRB prior to implementation. 
11.5 Unscheduled Office Visits 
Investigators may see the subjects, at their professional discretion, outside of the time points 
described in the study protocol.  If an adverse event (AE) is reported during an unscheduled visit, 
the AE should be documented per Section 12.0 Adverse Event Reporting.  No additional data 
collection or Case Report Forms are required at the unscheduled visit. 
11.6 Protocol Deviations and Violations 
The Investigator(s) agrees to conduct the study in accordance with this protocol.  For the purpose 
of this study, only violations that affect the subject’s rights, safety, or welfare, or the integrity of 
the data will be recorded.   

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11.6.1 A protocol violation can be described as accidental or unintentional change to, or 
non-compliance with the IRB approved protocol without prior Sponsor and IRB approval. 
Violations generally increase risk and/or decrease benefit, affects the subject's rights, 
safety, or welfare, or the integrity of the data.  Examples include failure to obtain valid 
informed consent (e.g., obtained informed consent on an unapproved consent form), loss of 
laptop/computer that contained identifiable and private information about subjects or not 
following inclusion/exclusion criteria. 
Any deviations to inclusion or exclusion criteria must be submitted to Zimmer Biomet and 
the reviewing IRB, where applicable, for analysis and approval prior to subject enrollment.  
All protocol violations shall be reported to Zimmer Biomet within 24 hours and to the 
reviewing IRB per policy.  A Protocol Violation Form shall be completed that includes a 
full explanation of the event and outcome. 
The Investigator will assist Zimmer Biomet in corresponding with the reviewing IRB, 
where appropriate, to determine the appropriate course of action. 
11.6.2 Protocol deviations will not be collected for this study.  A protocol deviation is an 
accidental or unintentional change to or non-compliance with the research protocol that 
does not increase risk or decrease benefit or does not have a significant effect on the 
subject's rights, safety or welfare, and/or on the integrity of the data.  A deviation may be 
due to the research subject’s non-adherence or an unintentional change to or non-
compliance with the research protocol on the part of a researcher.   
11.7 Withdrawal and Study Re-Entry 
During the course of the study, it is possible that subjects will be withdrawn from the study. 
Factors leading to subject withdrawal may include, but are not limited to, the following: 
Subject Withdrawal – A subject may voluntarily withdraw from the study at any time without 
prejudice or affecting their future medical treatment. Investigators may withdraw a subject due to 
non-compliance with the protocol or follow-up questionnaire schedule, or for any other reason 
per their professional opinion. The date and reason for subject withdrawal is to be documented 
on the Study Exit form.  
If a subject is withdrawn or terminated due to medical safety considerations because of an 
adverse event, the adverse event must be followed by the investigator to satisfactory resolution 
or until the investigator determines the event to be chronic or clinically stable. All study data 
related to event is to be recorded.  
Subject Lost to Follow-Up – If the subject does not complete the required questionnaires and the 
Investigator or Study Coordinator has attempted to contact that subject at least three times via 
telephone and receives no response, the subject may be deemed to be lost to follow-up. The 
research staff will document the attempts to contact the subject. The final attempt to contact the 
subject will be performed by register/return receipt mail. The receipt will be placed in the 

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subject’s binder. A study Exit Form must be completed.  
Should a subject who previously chose to withdraw or was considered lost-to-follow-up wishes 
to re-enter the study, a new Informed Consent will be required.  The site may resume scheduled 
follow-up visits from the subject’s last follow-up visit.   
Subject Death – Should a subject expire, complete the Adverse Event and Study Exit Form. 
Submit copies of the death certificate, autopsy report (if applicable and available) and source 
documents related to the death. The Investigator will make written notification to the IRB upon 
the death of a subject in the study. 
When a subject withdraws or is withdrawn, all study procedures completed and data collected 
prior to the date of withdrawal will be submitted to the sponsor and included in the study 
database, unless the subject requests otherwise in writing. 
 
12.0 Adverse Event Reporting   
An adverse event (AE) is defined as an untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (or change or worsening of a pre-existing medical condition) in 
a patient, which may or may not have an association with the device. In addition an adverse 
device effect is defined as ‘any untoward and unintended response to a medical device’. 
For this study, only AEs which are possibly or definitely related to the device or procedure 
will be reported to the sponsor.  The determination whether the AE is related to the device or 
procedure will be based upon whether a causal relationship between the device or procedure and 
the AE is at least a reasonable possibility, i.e., the relationship cannot be ruled out. A causal 
relationship cannot be ruled out if, in the medical judgment of the investigator, the effect follows 
a reasonable temporal association with the use of the device. See Section 12.1.   
In the event there is an exacerbation of the pre-existing medical condition or symptoms (due to 
the device or study related procedure), then an AE must be reported.  
12.1 Relationship to study device or procedure   
The relationship to the study device or procedure should be rated as follows: 
• None (definitely not related): there is no relationship between study device or 
procedure and the event.  
• Possible (remote possibility, possibly, or probably related): the relationship 
between study device or procedure could exist if there is no contradicting 
evidence that can reasonably explain the Subject’s condition.  
• Definite (definitely related): the relationship between study device or procedure 
and event does exist and is confirmed upon further investigation by the 
investigator. 

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• Subjects should be encouraged to report AEs spontaneously and may volunteer AE 
information at any time. At each evaluation, the investigator will determine whether an 
AE has occurred. If it is determined that an AE has occurred, the investigator should 
obtain all the information required to complete the appropriate AE form(s). If an event 
occurs at an outside institution, the investigator should attempt to obtain, if possible, 
required AE information to report to the Sponsor. 
12.2 Adverse Event Data Collection 
The Adverse Event Form will collect the following: 
• Description of complication 
• Date of onset 
• Severity/Intensity of symptoms 
o Mild: Event/symptom is transient and well tolerated by the subject. 
o Moderate: Event/symptom causes discomfort and interferes with routine 
activities of the subject. 
o Severe: Event/symptom interferes considerably with the routine activities 
of the subject or causes inability to work. 
• Duration 
• Relationship to surgical procedure 
• Relationship to product 
• Treatment 
• AE Outcome 
 
12.3 Events Followed to Resolution 
Any Adverse Event considered by the Investigator to be possibly or definitely related to the 
Subchondroplasty procedure should be followed over the study period until resolution or until 
the Investigator determines the event is chronic or clinically stable.  
12.4 Serious Adverse Events 
A Serious Adverse Event (SAE) is described as any adverse event that is: 
• Fatal; 
• Life-threatening*; 
• Results in permanent impairment of a body function or permanent damage to body 
structure; or 
• Necessitates medical or surgical intervention, including hospitalization 
* NOTE: the term “life-threatening” refers to an event in which the subject was at a risk of 
death at the time of the event; it does not refer to an event which hypothetically might have 
caused death if it were more severe. 
If an AE is determined to be serious (i.e., an SAE), the Investigator(s) will determine the 

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relationship of the adverse event to the procedure, device, or any commercial products used 
during the period of the study and complete a Serious Adverse Event Form. Death is 
considered to be an outcome of an Adverse Event and documented on the Serious Adverse Event 
Form.  The actual cause of death (rather than the term “death”) should be recorded on the form.  
All SAEs will be followed until resolution or the Investigator judges the event to be chronic or 
stable.   
The Investigator must report all SAEs that meet the criteria below to a Zimmer Biomet Study 
Representative within twenty-four (24) hours after becoming aware of the incident: 
• Definitely or possibly related to the Study Procedure AND unexpected 
The Investigator is responsible for notifying the IRB of all Adverse Events, including SAEs, in 
accordance with local regulations and institutional policies.  
If an Unanticipated Serious Adverse Device Effect (USADE) is identified by the Sponsor, it will 
be promptly reported to concerned Investigators and regulatory authorities as required by 
applicable regulatory requirements. If applicable per their reporting requirements, the 
Investigator or Designee will report the USADE to their IRB or EC. 
13.0 Assessment of Safety 
All reports of Adverse Events will be entered into the study database and evaluated by the 
Sponsor or their designee on a regular basis throughout the study.  These reports will be made 
available to the Investigator for preparation of IRB continuing review reports, when requested.   
Individual and aggregated events will be reviewed for consistency with expected events, for both 
severity and rate of incidence.  Individual events or trends in events that appear to impact subject 
safety are reviewed by Zimmer Biomet management to determine if a change in the protocol or 
termination of the study is warranted. These decisions will be promptly communicated to all 
Investigators and local IRBs. 
14.0 Statistical Considerations and Methodology 
Data collected in this study will be summarized descriptively and will be the basis of study 
reports. Descriptive summaries will be used to generate an overall summary of the clinical 
performance of the Subchondroplasty® Procedure in the foot/ankle cases and may be used for 
reports or to support presentations or publications. 
Summaries will routinely describe categorical data as counts and percentages and ninety-five 
percent confidence limits will generally be used to assess categorical differences. Routine 
summaries describing continuous data will be in the form of means, medians, standard 
deviations, minima and maxima; ninety-five percent confidence intervals will be used to contrast 
differences. Routine summaries of return to function, patient outcomes measures, etc. will 
generally be described via the Kaplan-Meier method and these will generally be accompanied 
with the corresponding crude rates (expressed as percentages).  Routine summaries of 
complication data will be in the form of frequencies and percentages. Summaries may be further 
generated for strata within the study population, (e.g., males and females, different cut-points in 

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the body mass index continuum, etc.). Subject confidentiality will be protected at all times and 
subject identifiers will not be included in study summaries. 
15.0 Data Management  
15.1 
Data Collection 
Data will be recorded using an electronic data capture (EDC) platform provided by Zimmer 
Biomet.  Zimmer Biomet personnel will provide access, training and user support to all sites.  
Investigative sites will be required to have broadband internet access with standard firewall 
protection features.   
Data are to be recorded utilizing subjects’ source documentation, which includes medical 
records, operative and clinic notes, ancillary services reports, subject surveys and in some cases 
Case Report Forms. The subject-completed surveys are considered source documentation for this 
information. This may include electronically collected ePRO surveys where the direct data entry 
of survey data by the subject constitutes electronic source, paper surveys completed and 
submitted by the subject, or paper surveys completed on behalf of the subject by the site 
coordinator during phone interviews. Case Report Forms or certified copies of Case Report 
Forms may also serve as source documentation when the information is in addition to what is 
typically entered into a subject’s medical record (e.g., fields documenting SCP time on the 
Surgical Documentation Form). Any Case Report Forms used as source documentation are to be 
labeled as such and made part of the subjects’ case histories.  Data are to be recorded accurately 
and in a timely manner following each event.   
Questions regarding the content of the forms should be directed to the Zimmer Biomet Study 
Representatives. 
15.2 
Data Submission 
Data will be recorded using an electronic case report form (eCRF) platform. If there is missing or 
out-of-range information, the system will give immediate feedback to the individual making the 
entry and allow for correction and/or the assignment of a data query.   
Submitted forms will undergo review by Zimmer Biomet personnel and questions or requests for 
corrections will be sent to the Investigator via the EDCs electronic data query system. All 
corrections are to be made by the site coordinator within the EDC system as well as any needed 
corrections to paper CRFs following GCP guidelines. Zimmer Biomet personnel will review 
corrected information in the study database. 
16.0 Records and Reporting  
16.1 
Disclosure of Health Information 
The use or disclosure of all protected health information will comply with the Health Insurance 
Portability and Accountability Act (HIPAA). Any information provided to Zimmer Biomet will 
be identified only by a subject ID and date of surgery. All information will be treated with strict 
adherence to professional standards of confidentiality and will be filed at Zimmer Biomet under 

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adequate security and restricted accessibility by clinical personnel.   
16.2    Auditing and Inspecting 
The Investigator will permit study-related monitoring visits, quality assurance audits, and 
inspections by the IRB, the Sponsor, government agencies, and other local health authorities as 
necessary to ensure proper conduct of the study in terms of collection and recording of data and 
maintaining records. Representatives of Zimmer Biomet should be allowed access to relevant 
study materials, including source documents of data collected as part of this study.  
Every precaution will be taken to protect the privacy of research subjects and the confidentiality 
of their personal information when using or disclosing protected health information (PHI), or 
when requesting PHI from others.  Reasonable efforts will be made to limit the disclosures to the 
minimum necessary to accomplish the intended purpose of the use, disclosure, or 
request. Zimmer Biomet strictly complies with the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA) Privacy and Security Rules.   
16.3 
Maintenance of Records 
The Investigator is to maintain a copy of all study records and source documentation, including 
signed Informed Consent Forms and HIPAA Authorization, for a minimum of 6 years following 
the last protected health information disclosure.  This time period may be greater if required by 
reviewing IRB or institutional policies.   
17.0 Materials and Supplies 
17.1 
Study Materials 
Zimmer Biomet will provide each investigative site with Investigator Notebook including the 
protocol, paper copies of case report forms and logs, study tools, and subject stipend cards.  The 
Zimmer Biomet Study Representatives are available to provide additional supplies upon request.  
17.2 
Subchondroplasty Products 
The AccuFill bone substitute material and Subchondroplasty Instrumentation are to be ordered 
through the Investigator’s Zimmer Biomet Sales Representative. Specific information on the 
products used will be recorded on study Case Report Forms, including lot numbers. 
18.0 Publication Policy 
Institution or Investigators may publish, present, or use any results arising out of the performance 
of this Study for its or their own publication, presentation, instructional, or non-commercial 
research objectives provided that the publication, presentation, or use does not disclose any 
Confidential Information furnished by Sponsor, occurs only after completion of the Study, and 
contains only final Study data and analysis, unless otherwise approved by Sponsor.   
Institution and each Investigator agrees that any proposed publication or presentation relating to 
the Study conducted under this Agreement will be submitted to Sponsor for review (not for 
approval or disapproval) at least thirty (30) days prior to submission for publication or 

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presentation.  In the event that the proposed publication or presentation contains patentable 
subject matter that needs protection, Institution and Investigators will, upon request received 
from Sponsor within the thirty (30) day review period, delay the publication or presentation for 
an additional ninety (90) days to allow Sponsor to file a patent application.  Sponsor will have 
the right to require deletion of any Confidential Information or other proprietary information 
belonging to the Sponsor or information identifying Qualified Participants in the Study, unless 
otherwise required by law.   
Notwithstanding the foregoing, to the extent the Study is part of a multi-center study, the 
Institution and each Investigator agree that the first publication of the results of the Study will be 
made in conjunction with the presentation of a joint multi-center publication of the Study results 
with the investigators and institutions from all Study sites contributing data.  
 

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19.0 References 
1. 
Eriksen EF, Ringe JD. Bone marrow lesions: a universal bone response to injury? 
Rheumatol Int 2012; 32(3):575-84. 
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Felson DT, Chaisson C, Hill CL, Totterman SMS, Gale ME, Skinner KM, Kazis L, Gale 
DR. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern 
Med 2001; 134(7):541-9. 
3. 
Hofmann S, Kramer J, Vakil-Adli A, Aigner N, Breitenseher M. Painful bone marrow 
edema of the knee: differential diagnosis and therapeutic concepts. Orthop Clin North 
Am 2004; 35(3):321-33, ix. 
4.  
Saltzmann CL, Salamon ML, Blanchard GM, Huff T, Hayes A, Buckwalter JA, 
Amendola A. Epidemiology of ankle arthritis: report of a consecutive series of 639 
patients from a tertiary orthopaedic center. Iowa Orthop J 2005; 25:44-46. 
5. 
Orr JD, Sabesan V, Major N, Nunley J. Painful bone marrow edema syndrome of the foot 
and ankle. Foot & Ankle Int 2010; 31:949-953. 
6. 
Wilson AJ, Murphy WA, Hardy DA. Transient osteoporosis: transient bone marrow 
edema? Radiology 1988; 167:757-760. 
7. 
Gigena LM, Chung CB, Lektrakul, N, Pfirrmann CWA, Sung MS, Resnick D. Transient 
bone marrow edema of the talus: MR imaging findings in five patients. Skeletal Radiol 
2002; 31:202-207. 
8. 
Fernandez-Canton G, Casado O, Capelastegui A, Astigarraga E, Larena JA, Merino A. 
Bone marrow edema syndrome of the foot: one year follow-up with MR imaging. 
Skeletal Radiol 2003; 32:273-278. 
9. 
Rios AM, Rosenberg ZS, Bencardino JT, Rodrigo SP, Theran SG.  Bone marrow edema 
patterns in the ankle and hindfoot: Distinguishing MRI features. AJR 2011; 197:W720-
W729.  
10. 
Zanetti M, Steiner CL, Seifert B, Hodler J. Clinical outcome of edema-like bone marrow 
abnormalities of the foot. Radiology 2002; 222:184-188. 
11. 
Miller JB, Dunn KW. Subchondroplasty of the ankle: A novel technique.  FAOJ 2015; 
8(1):7. Accessed at: https://faoj.org/2015/03/31/subchondroplasty-of-the-ankle-a-novel-
technique/. 
12.  
Sharkey, PF, Leinberry CF, Parvizi J. Subchondral bone marrow lesions associated with 
knee osteoarthritis. Am J Orthop 2012; 41(9):413-7. 
13.   
Colon DA,  Yoon BJV, Russell TA, Cammisa FP, Abjornson C. Assessment of the 
injection behavior of commercially available bone BSMs for Subchondroplasty® 
procedures. The Knee 2015; http://dx.doi.org/10.1016/j.knee.2015.06.017. 
14.  
Cohen SB, Sharkey PF. Subchondroplasty for Treating Bone Marrow Lesions. J Knee 
Surg 2015; Thieme Open access: https://www.thieme-connect.com/DOI/DOI?10.1055/s-
0035-1568988 .Appendices