Association of Cartilage Oligomeric Matrix Protein Biomarker Levels in Femoroacetabular Impingement and Hip Osteoarthritis
Sep 2016 – Apr 2017
Project descriptionMy own scientific study researching the relationship between a biomarker and an early form of arthritis to attempt to discover a new way that hip arthritis could be diagnosed earlier in patients.
The study was done in conjunction with Augurex Life Science Corporation co-founder Dr. Anthony Marotta, founder and president of Arthritis Consumer Experts Cheryl Koehn, and Dr. Jolanda Cibere of Arthritis Research Canada.
1. Association of Cartilage Oligomeric Matrix Protein Biomarker
Levels in Femoroacetabular Impingement and Hip Osteoarthritis
Hank Lendvoy; Cheryl Koehn; Anthony Marotta, Ph.D; Jolanda Cibere, MD, PhD;
Hank Lendvoy
Sentinel Secondary School
Email: hanklendvoy@gmail.com
Contact Information References
• COMP is not statistically significant with FAI or MRI-
OA in the context of this cohort
• Results refine the search for osteoarthritis’s first
early diagnosis biotechnological strategy
Conclusions
Introduction
Osteoarthritis
• most common form of arthritis
• affects 31.5 million people in North America and
costs $68 billion in annually1
• has no pharmaceutical or early diagnostic
solutions
• mainly effects the finger, knee, and hip joints
Hip Osteoarthritis (Hip OA)
• is a degenerative hip joint disease
• is an emerging field of study in osteoarthritis2
• hip pain negatively effect posture
• leads to other physical impairments
Femoroacetabular impingement (FAI)
• is a degenerative hip joint disease similar to hip
OA3
• appears in Pincer, Cam, and combined forms
• is thought to be the primary precursor for hip OA
Biomarkers
• measure a substance that helps to predict or
diagnose a certain clinical outcome
• minimally impacted by variables (such as age,
weight, sex, etc)
Cartilage oligomeric matrix protein (COMP)
• is a biomarker of cartilage degradation4
• is predictive of hip OA
Two tailed T-Test
• showed that COMP is not statistically significant with
FAI or MRI-OA for an Independent Samples Test
Logistic Regression Analysis
• showed that with the variables taken into account,
COMP is still not statistically significance with FAI or
MRI-OA
• COMP is a marker of OA but statistical analysis
power was reduced because of small group size
for subjects with MRI-OA (n=12)
Discussion
Acknowledgements
Picture 1. Diagram of different forms of FAI
Objectives
• Can COMP associate FAI with hip OA
• Is COMP a viable clinical marker for the
early diagnosis of hip OA
Enzyme-Linked Immunosorbent Assay (ELISA)
• uses quantitative sandwich technique to measure COMP in
serum5
• BioVendor’s Human Cartilage Oligomeric Matrix Protein
ELISA used
• procedure programmed into automated DSX 4-plate ELISA
Processing System
DSX 4-plate ELISA Processing System Automation
• BioVendor’s ELISA procedure programmed using Revelation
Software
• both plates formatted based on BioVendor Standards, QCs,
Blanks, and Samples
• 4 ambient incubations programmed at 300 rpm (1 hour, 1
hour, 30 minutes, 10 minutes)
• reagent dispensing, dilution factors, and wash cycles
programmed to run both plates simultaneously
Materials and Methods
Two tailed T-test
• 95% confidence interval of difference crossed 0 (lower
value of -165.6 to upper value of 55.7)
• P-value of 0.33
Logistic Regression Analysis
• for every 1 mg/mL increase in COMP there was a 1.3-
fold increase risk of having FAI
• P-value of 0.7
FAI ASSOCIATION
Table 2. Results from a logistic regression analysis performed to asses COMP’s
statistical significance with FAI taking into account age, sex, and BMI’s effects on COMP
levels.
Picture 2. Diagram showing the ELISA procedure
Cohort Recruitment
• 500 subjects offered to participate through random dialing
• Caucasian, aged 20 to 49
• excluded if they had total hip replacement or other
contraindications to MRIs
• FAI defined as lateral center edge angle > 40°, alpha angle
> 55° or presence of a cross-over sign
• MRI-OA was defined based on knee OA criteria
• cartilage damage, bone marrow, etc
• final cohort (n=182) supplied serum samples
IMPAKT-HiP Cohort
• 182 subjects submitted serum samples
• includes subject’s with FAI and hip OA
Cohort Descriptives put into table
• 142 (out of 182) Caucasian subjects
• mean age of 43.5
• 65.5% female
• 50.0% with FAI
• 8.5% with radiographically defined MRI-OA
• 50.7% had hip pain.
Patient Cohort
Statistical Analysis
• two tailed T-test performed
• logistic regression analysis performed
• sex, BMI, and age taken into account
Factors Affecting COMP
• Sex, disease progression, age, weight, BMI
Statistical Analysis Plan
95% C.I. for
EXP(B)
Sig. Exp(B) Lower Upper
COMP
(mg/mL)
.665 1.275 .424 3.834
Two tailed T-test
• 95% confidence interval of difference crossed 0 (lower
value of -358.0 to upper value of 37.6)
• P-value 0.1
Logistic Regression Analysis
• for every 1 mg/mL increase in COMP there was a 2.2-
fold increase risk of having MRI-OA
• P-value of 0.3
MRI-OA ASSOCIATION
Table 3. Results from a logistic regression analysis performed to asses COMP’s statistical
significance with MRI-OA taking into account age, sex, and BMI’s effects on COMP levels.
95% C.I. for
EXP(B)
Sig. Exp(B) Lower Upper
COMP
(mg/mL)
.312 2.180 .481 9.884
Automation
Picture 3. DSX 4-plate ELISA Processing System
Picture 4. Screenshot of timeline of COMP assay from Revelation Software
1Hunter, David J., Michael Nevitt, Elena Losina, and Virginia Kraus. "Biomarkers for Osteoarthritis: Current Position and Steps towards Further Validation." Best Practice & Research. Clinical
Rheumatology. U.S. National Library of Medicine, Feb. 2014. Web. 20 Nov. 2016.
2"Hip Impingement." WebMD. WebMD, n.d. Web. 09 Apr. 2017. <http://www.webmd.com/pain-management/hip-impingement-causes-treatments>.
3Hip Impingement. (n.d.). Retrieved April 07, 2017, from http://www.webmd.com/pain-management/hip-impingement-causes-treatments
4Tseng, Susan, A. Hari Reddi, and Paul E. Di Cesare. "Cartilage Oligomeric Matrix Protein (COMP): A Biomarker of Arthritis." Biomarker Insights. Libertas Academica, 2009. Web. 10 Apr. 2017.
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716683/>.
5 "Enzyme-linked Immunosorbent Assay (ELISA) Overview." Thermo Fisher Scientific. N.p., n.d. Web. 10 Apr. 2017. <https://www.thermofisher.com/ca/en/home/life-science/protein-
biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/overview-elisa.html>.
BMI Percent of Cohort
BMI <25.00 30.0
BMI 25.1 – 29.9 37.3
BMI >30.0 24.6
Table 1. BMI characteristics of the cohort represented categorically