Effects of Unloader Bracing in Clinical Outcome and Articular Cartilage Physiology Following Microfracture of Isolated Chondral Defects
Phase: NA
Conditions: Cartilage Loss, Microfracture
Sponsor: Stanford University

  
Effects of Unloader Bracing in Clinical Outcome and Articular Cartilage 
Physiology Following Microfracture of Isolated Chondral Defects 
Study Protocol 
NCT02016300 
December 13, 2011 
 

  
Effects of Unloader Bracing on Clinical Outcome and Articular 
Cartilage Regeneration following Microfracture of isolated 
Chondral Defects 
Background 
The management of articular cartilage defects continues to be one of the most challenging 
clinical problems for orthopaedic surgeons. Articular cartilage is a highly organized tissue 
with complex biomechanical properties and substantial durability. However, it has a poor 
intrinsic capacity for healing, and defects resulting from trauma can result in considerable 
functional impairment and lead to subsequent joint degeneration and osteoarthritis. 1  
Bone marrow stimulation through ‘microfracture’ is the most frequently used technique for 
treating small symptomatic defects of the articular cartilage in the knee. It is a technically 
straightforward procedure, and the costs are low compared with those of other treatment 
modalities. Microfracture involves perforation of the subchondral plate in order to recruit 
mesenchymal stem cells from the bone marrow space into the lesion2. The formation of a 
stable blood clot that maximally fills the chondral defect is important, and it has been 
correlated with the success of bone marrow stimulation procedures1. 
Two aspects of post-operative rehabilitation are thought to be critical to the success of 
microfracture. First, protected weight-bearing for 8 weeks post-operatively protect the clot 
from shear forces, which may disrupt the clot and prevent healing.3,4 Second, continuous 
passive motion is believed to encourage stem cell differentiation along a chondral pathway.4,5 
During rehabilitation following microfracture, an unloading valgus brace may further 
enhance clot stability by protecting it from disruptive shear forces during motion. Unloader 
braces apply an external, valgus force by creating a three-point bending moment along the 
knee, which decreases the force on the medial compartment. 
The aim of this pilot study is to determine whether the use of post-operative unloading brace 
will improve outcomes of the microfracture procedure for treatment of isolated cartilage 
lesions. 

  
Study Design (Pilot Study) 
Recruitment 
A pilot study will be carried out at two centers. 20 patients will be enrolled at each center and 
be randomized to 2 groups. Patients will be identified from preoperative clinical and 
radiographic evaluation as potential candidates for the study, however as eligibility will 
depend on arthroscopic assessment of the cartilage lesion at the time of surgery final 
enrollment will occur immediately post operatively.  
Inclusion criteria include a discrete, contained chondral defect less than 2cm2 in size located 
on the medial or lateral femoral condyle, age between 18-40 years, and overall neutral lower 
limb mechanical alignment (<5 degrees varus or valgus).  Exclusion criteria include previous 
chondral procedures, osteoarthritis (Kellegren-Lawrence Grade ≥2), or significant 
concomitant knee pathology such as a meniscal tear requiring treatment or a ligamentous 
instability.  Patients who have previously undergone ACL reconstruction or meniscal repair 
will still be eligible for inclusion in the study.  
Initial post-operative protocol 
All patients will participate in physical therapy two times per week, use a continuous passive 
motion device for eight weeks and will have no ROM restrictions. Following enrollment, 10 
patients will be randomized into one of two groups at each center. Group 1 will be fitted with 
the Ossur Unloader One brace. Group 2 will be treated without a brace. At Center 1 (USA), 
patients will be initially kept non-weight bearing for a period of 8 weeks prior to applying an 
unloader brace. At Centre 2 (Japan), patients will wear an off-loading brace and commence 
weight bearing immediately post-operatively. Non-bracing group will be NWB for 8 weeks 
at both centers. 
 
 
 

  
Outcome Measures 
Radiographic outcome will be assessed using baseline, 6 month, and one and two year MRI 
scans which will assess the quality of the cartilage repair. T1 Rho and T2 mapping will be 
used to assess regenerate cartilage composition compared to surrounding normal cartilage, 
surface integrity, average cartilage thickness and the percentage to which the defect is filled. 
MRI mapping protocols investigate cartilage health by looking at glycosaminoglycan (GAG) 
concentration. Higher concentrations of GAG generally indicate healthier cartilage. 
Moreover, correlations have been found between T2 values and cartilage hydration, collagen 
fiber orientation, and loss of type 2 collagen, suggesting some degree of specificity for 
targeting the spatial collagen architecture of the matrix.6 
Clinical outcome will be assessed at MRI follow-up time points using: The Knee injury 
and Osteoarthritis Outcome Score (KOOS) questionnaire is a standard clinical tool used to 
evaluate short-term and long-term symptoms and function in subjects with knee injury and 
osteoarthritis. It is broken up into five subcategories: Knee symptoms, knee pain, Function in 
daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality 
of Life (QOL). The KOOS is a validated, reliable and responsive self-administered 
instrument that can be used for short-term and long-term follow-up of osteoarthritis and will 
given to our patients to evaluate the effect of the unloading braces. The KOOS incorporates 
the commonly used WOMAC survey. 
Tegner activity level scale will be used to establish standardized activity levels pre and post 
treatment. VR-12 quality of Life questionnaire will be used to establish changes in quality of 
life. Lysholm score will be used to reflect symptoms with activities of daily living. VAS 
(Visual Analog Scale) will be used to determine the level of patient pain at each visit. 
 
 
 
 

  
Schedule of Appointments 
Visit 1 (T=0)  
Visit 1 will be the baseline visit and will take place at the first post operative visit.  
Participants will undergo the informed consent process.  Once signed, participants will 
answer standardized questionnaires (see above), get fitted for the brace (if in bracing group), 
and undergo baseline MRI scans and x-rays to evaluate alignment. Wearing of the brace will 
commence at the time of weight bearing, which will occur immediately post-operatively in 
Centre 2 (Japan) and 8 weeks post operatively at Centre 1 (USA). 
Brace fitting 
Each participant will be fitted by a licensed orthotist for the Unloader brace. 
 
Imaging 
Each participant will undergo a pre-study series of X-rays that are standard for osteoarthritis 
examination.  This series consists of a front-view (AP) X-ray of the knees, a sideways 
(lateral) view, and a one with the knee flexed at 45° (Rosenberg).  There will also be a long 
standing X-ray (36") that will film the lower extremities. These films will measure any mal-
alignment present. 
A MRI scan during the first visit will examine cartilage physiology.  The scans will take 
place at the Stanford Medical Outpatient Center or Stanford Medical Lucas Imaging Center 
with a 3T scanner.  Subjects will undergo 2D-T2 mapping, 3D-T2 mapping, and 3D-T1rho 
mapping.  These scans take approximately 12, 10, and 6 minutes, respectively.  The total 
time for the first visit will last approximately 2 hours. 
Brace wear and documentation 
All patients will be provided with a hard copy bracing diary for the 6-month study duration. 
Patients will be instructed to document the number of hours for which they wear the brace 
each day. Diaries will be collected at Visit 2 and daily and weekly averages will be 
calculated for all patients. 

  
Each Unloader brace will be equipped with an iButton temperature sensor that acquires 
temperature readings every 20 minutes to objectively document brace wear. The temperature 
threshold to determine brace wear is set at 25C. The iButton captures and stores these 
measurements for 1 month after which it must be reprogrammed; all participants will 
therefore undergo five iButton swaps. These visits will be managed by the orthotist who 
performs the initial brace fitting. The final iButton will be obtained at Visit 2. iButton data 
files will be post-processed by Duane Romo and daily and weekly averages calculated for 
each participant. These values will be compared with the bracing diaries completed by each 
patient. 
Visit 2 (T=6 Months) 
Visit two will consist of quantitative MRI scans conducted at the Stanford Medical 
Outpatient Center or the Stanford Lucas Imaging Center.  The patient will also complete the 
same standardized questionnaires as in the first visit.   
Visit 3 (T= 12 months) 
The patient will return for another quantitative MRI scan and to answer the standardized 
questionnaires.  
Visit 4 (T= 24 months) 
The patient will come back again for a final MRI mapping scan and to answer the 
standardized questionnaires.  
Benefits 
All subjects requiring bracing will receive a fitted Unloader One off the shelf brace as 
compensation for their participation in the study.  
Budget 
Standard treatment costs, which the study sponsor will NOT be responsible for, include: 
1. office visits 

  
2. standard x-ray series 
3. off-loader bracing (insurance reimbursement portion)  
Sponsor study costs (per study site): 
Year 1: 
1. Any patient costs for Unloader brace NOT covered by insurance (unknown) 
2. Biologic MRI scanning and T2 mapping analysis of 20 patients                                                 
@ 4 scanning sessions @$600/scan 
 
 
 
 
  
   
 
3.  MRI analysis (post doc radiologist @ 50% effort)=          
 
 
   
  
4. Study coordinator 
 
 
 
 
 
 
 
   
 
          
 
Year 2:
 (MRI analysis and study coordinator only) 
 
 
References 
 
1 Bedi A, Feeley BT, Williams RJ. Management of Articular Cartilage Defects of the Knee. The 
Journal of Bone and Joint Surgery 2010; 92: 994–1009. 
2 Knutsen G, Engebretsen L, Ludvigsen TC, et al. Autologous chondrocyte implantation compared 
with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 2004; 86-A: 455–64. 
3 Safran MR, Seiber K. The evidence for surgical repair of articular cartilage in the knee. J Am 
Acad Orthop Surg 2010; 18: 259–66. 
4 Hurst JM, Steadman JR, O'Brien L, Rodkey WG, Briggs KK. Rehabilitation following 
microfracture for chondral injury in the knee. Clin Sports Med 2010; 29: 257–65–viii. 
5 Rodrigo JJ, Steadman JR, Silliman JF, Fulstone HA. Rodrigo: Improvement of full-thickness 
chondral defect... - Google Scholar. Am J Knee Surg, 1994. 
6 Oneto JMM, Ellermann J, LaPrade RF. Longitudinal evaluation of cartilage repair tissue after 
microfracture using T2-mapping: a case report with arthroscopic and MRI correlation. Knee Surg 
Sports Traumatol Arthrosc 2010; 18: 1545–50.