Knee osteoarthritis (OA) is
typically a slowly progressive disorder, but at least 1 in 5 people
develop advanced-stage knee OA with dramatic rapidity (i.e., normal to
advance-stage disease within 4 years; often within 12 months).
Therefore, we urgently need to be able to detect which individuals are
at greatest risk of accelerated knee OA prior to the development of
this debilitating disease. Our research has quantified structural
pathology on magnetic resonance images (MRIs) using data from the
Osteoarthritis Initiative. We have determined that ligamentous
degeneration, effusion/synovitis, destabilizing meniscal tear, and
diffuse cartilage alterations may serve as prognostic biomarkers as
they precede the onset of accelerated KOA.
Harkey
MS , Davis JE, Price LL, Ward RJ, MacKay JW, Eaton CB, Lo
GH, Barbe MF, Zhang M, Pang J, Stout AC, Lu B, McAlindon TE, Driban JB.
Composite Quantitative Knee Structure Metrics Predict the Development
of Accelerated Knee Osteoarthritis: Data from the Osteoarthritis
Initiative. Published in BMC
Musculoskeletal Disorders. 2020 May. 21(299):1-10.
Driban JB, Davis JE, Lu B, Price
LL, Ward R, MacKay J, Eaton CB, Lo GH, Barbe M, Zhang M, Pang J, Stout
AC, Harkey MS ,
McAlindon TE. Accelerated Knee Osteoarthritis is Characterized by
Destabilizing Meniscal Tears and Pre-Radiographic Structural Disease
Burden. Published in Arthritis
and Rheumatology. 2019 Jul; 71(7): 1089-1100. PMID:
30592385. PMCID: PMC6594896.
Harkey
MS , Davis JE, Lu B, Price LL, Ward R, MacKay J, Eaton
CB, Lo GH, Barbe MF, Zhang M, Pang J, Stout AC, McAlindon TE, Driban
JB. Early pre-radiographic structural pathology precedes the onset of
accelerated knee osteoarthritis. Published in BMC Musculoskeletal Disorders.
2019
May; 20(241): 1-10. PMID: 31113401. PMCID: PMC6530034.
Harkey
MS , Davis JE, Lu B, Price L, Eaton CB, Lo GH, Barbe MF,
Ward R, Zhang M, Liu SH, Lapane KL, MacKay JW, McAlindon TE, Driban JB.
Diffuse Tibiofemoral Cartilage Change Prior to the Development of
Accelerated Knee Osteoarthritis: Data from the Osteoarthritis
Initiative. Published in Clinical
Anatomy. 2019 Apr; 32(3): 369-378. PMID: 30521068. PMCID:
PMC6414263.
Davis JE, Harkey MS , Ward R,
MacKay J, Lu B, Price LL, Eaton CB, Barbe MF, Lo GH, McAlindon TE,
Driban JB. Effusion-Synovitis and Infrapatellar Fat Pad Signal
Intensity Alteration Differentiate Accelerated Knee Osteoarthritis.
Published in Rheumatology.
2019 Mar; 58(3): 418-426. PMID: 30346594. PMCID: PMC6381765.
Decline in cartilage health is
a hallmark sign of osteoarthritis, and ultrasound represents a valid,
clinically-accessible alternative to MRI to assess cartilage. We have
developed methods for assessing femoral cartilage area and average
cartilage thickness using novel semi-automated ultrasound processing
techniques. Additionally, we developed novel methodology to use
ultrasound to sensitively quantify femoral cartilage deformation
following an acute bout of physical activity, as well as characterizing
how the cartilage recovers throughout the first hour following loading.
We have demonstrated that individuals following knee injury present
with greater femoral cartilage thickness compared to their
contralateral limb, as well as a healthy control limb. Since one in
three individuals following knee injury will develop knee OA within a
decade, we believe that ultrasound represents a clinically feasible,
sensitive technique to detect cartilage swelling in early stages of
knee OA.
Lisee C, McGrath ML, Kuenze C,
Zhang M, Salzler M, Driban JB, Harkey
MS . Novel Semi-Automated Ultrasound Segmentation
Technique for Assessing Average Regional Femoral Articular Cartilage
Thickness. Accepted for Published in Journal
of Sports Rehabilitation. 2020 Mar.
Harkey
MS , Blackburn JT, Nissman D, Davis HC, Durrington I,
Rizk C, Kuismanen A, Pietrosimone B. Ultrasonographic Assessment of
Femoral Cartilage in Individuals with Anterior Cruciate Ligament
Reconstruction: A Case-Control Study. Published in Journal of Athletic Training.
2018
Nov; 53(11):1082-1088. PMID: 30615493. PMCID: PMC6333222.
Harkey
MS , Blackburn JT, Hackney AC, Lewek M, Schmitz R,
Nissman D, Pietrosimone B. Comprehensively Assessing the Acute Femoral
Cartilage Response and Recovery After Walking and Drop-Landing: An
Ultrasonographic Study. Published in Ultrasound
in Medicine & Biology. 2018 Feb, 44(2):311-20.
PMID: 29198383.
Harkey
MS , Davis H, Sierra-Arévalo L, Blackburn JT, Nissman D,
Pietrosimone B. The Association Between Habitual Walking Speed and
Medial Femoral Cartilage Deformation Following 30-Minutes of Walking.
Published in Gait
& Posture. 2018 Jan, 59:128-33. PMID: 29031137.
Harkey
MS , Davis H, Sierra-Arévalo L, Blackburn JT, Nissman D,
Pietrosimone B. Ultrasonographic Assessment of Medial Femoral Cartilage
Deformation Acutely Following Walking and Running. Published in Osteoarthritis and Cartilage.
2017 June, 25(6):907-13. PMID: 28043940.
Walking speed is a clinically
accessible physical function measure that is predictive of disability
in activities of daily living and mortality in older individuals.
Additionally, walking speed is a simple clinical outcome measure that
has implications for knee biomechanics that occur during gait. We
observed that individuals following knee injury who walked slower
presented with greater serum concentrations of cartilage breakdown
biomarkers, as well as worse femoral cartilage composition. We
demonstrated that slower walking speed was associated with greater
medial femoral cartilage deformation assessed with ultrasound.
Additionally, we have determined that longitudinal declines in walking
speed in individuals that develop accelerated knee OA are associated
with increasing bone marrow lesion and effusion volume. We have
determined that longitudinal declines in walking speed in individuals
that develop accelerated knee OA are associated with increasing bone
marrow lesion and effusion volume. We also demonstrated a one-year
decline in walking speed was associated with twice the risk, while an
increase in walking speed was associated with half the risk of
receiving a knee replacement in the compared to someone with no change
in walking speed. Therefore, walking speed is a clinically relevant
physical function outcome that
has important implications in declining knee joint health across a
continuum of people with and at risk for knee OA.
Harkey
MS , Lapane KL, Liu S, Lo GH, McAlindon TE, Driban JB. A
Decline in Walking Speed is Associated with Incident Knee Replacement
in Adults with and at Risk for Knee Osteoarthritis. Accepted for
Publication in the
Journal of Rheumatology. 2020 Jun. Epub Ahead of Print.
PMID: 32541076.
Harkey
MS , Price LL, McAlindon TE, Davis, JE, Lu B, Zhang M,
Eaton CB, Barbe M, Lo GH, Driban J. Association Between Declining
Walking Speed and Increasing Bone Marrow Lesion and Effusion Volume in
Individuals with Accelerated Knee Osteoarthritis. Published in Arthritis Care &
Research.
2019 Jan; 71(2):259-270. PMID: 29882630. PMCID: PMC6286681.
Pfeiffer SJ, Harkey MS , Stanley
LE, Blackburn JT, Padua DA, Spang JT, Marshall SW, Jordan JM, Schmitz
RJ, Nissman DB, Pietrosimone B. Associations between Slower Walking
Speed and T1ρ Magnetic Resonance Imaging of Femoral Cartilage following
Anterior Cruciate Ligament Reconstruction. Published in Arthritis Care and Research.
2018 Aug, 70(8):1132-1140. PMID: 29193888. PMCID: PMC5972050.
Harkey
MS , Davis H, Sierra-Arévalo L, Blackburn JT, Nissman D,
Pietrosimone B. The Association Between Habitual Walking Speed and
Medial Femoral Cartilage Deformation Following 30-Minutes of Walking.
Published in Gait
& Posture. 2018 Jan, 59:128-33. PMID: 29031137.
Pietrosimone B, Blackburn JT, Harkey MS , Luc BA,
Hackney AC, Padua DA, Driban JB, Spang JT, Jordan JM. Walking Speed as
a Potential Indicator of Cartilage Breakdown Following ACL
Reconstruction. Published in Arthritis
Care and Research. 2016 Jun, 68(6):793-800. PMID:
26502367.
One of the primary symptoms of
knee OA is a decline in physical function leading to physical
disability. Objective measures of physical function quantify functional
limitations by testing an individual’s performance on a variety of
daily tasks (e.g., short/long walking, standing from a chair).
Objective physical function is considered clinically important as worse
performance is associated with poor quality of life, a decline in
physical activity levels, and mortality in older adults and those with
or at risk for knee OA. We created patient-specific reference values
for objective physical function tests within subsets across both sexes
and a wide spectrum of age, radiographic knee OA severity, and BMI
categories. We created a mobile application that is downloadable on all
mobile App stores (OAFunction) as a clinically accessible way for
clinicians and researchers to use these references values. We have also
utilized therapeutic exercise coupled with transcutaneous electrical
nerve stimulation as a way to improve physical function in people with
knee OA.
Harkey MS, Lapane KL, Liu S, Lo GH, McAlindon TE, Driban
JB. A Decline in Walking Speed is Associated with Incident Knee
Replacement in Adults with and at Risk for Knee Osteoarthritis.
Accepted for Publication in the Journal
of Rheumatology. 2020 Jun. Epub
Ahead of Print. PMID: 32541076
Driban, JB,
Harkey MS, Price LL, Lo GH, McAlindon TE. The inverse
OARSI-OMERACT criteria is a valid indicator of the clinical worsening
of knee osteoarthritis: data from the Osteoarthritis Initiative.
Accepted for Publication in the Journal
of Rheumatology. 2020 Jun. Epub
Ahead of Print. PMID: 32541081
Harkey MS, Price LL, Reid KF, Lo GH, Liu S, Lapane KL,
Dantas LO, McAlindon TE, Driban JB. Patient-Specific Reference Values
for Objective Physical Function Tests: Data from the Osteoarthritis
Initiative. Published in Clinical
Rheumatology. 2020 Feb. Epub Ahead of
Print. PMID: 32030634
Pietrosimone B, Luc-Harkey BA,
Harkey MS, Davis-Wilson HC, Pfeiffer SJ, Schwartz TA,
Nissman D, Padua DA, Blackburn JT, Spang JT. Using TENS to Enhance
Therapeutic Exercise in Individuals with Knee Osteoarthritis. Accepted
for Publication in Medicine
& Science in Sport &;
Exercise. 2020 Apr. Epub Ahead of Print. PMID: 32251254
Luc-Harkey BA, Davis HC,
Harkey MS, Ryan ED, Gaynor B, Blackburn JT, Nissman DB,
Spang JT, Pietrosimone B. Quadriceps Rate of Torque Development and
Disability in Persons with Tibiofemoral Osteoarthritis. Published in
Journal of Orthopaedic
& Sports Physical Therapy. 2018 Sept,
48(9):694-703. PMID: 29787693
Assessing various biochemical
markers in serum allows for the quantification of dynamic physiological
processes related to knee OA. We demonstrated that greater body mass
index was associated with greater cartilage breakdown biomarkers in
people following knee injury, especially women. Maintaining or reducing
body mass index following knee injury may be protective for maintaining
optimal cartilage health. Additionally, assessing cartilage biomarkers
before and after a mechanical stimulus (e.g., walking, drop-landing)
provides an estimate of the dynamic cartilage response to functional
loading. We demonstrated that walking and drop-landing produced a
greater acute cartilage biomarker response when compared to a control
condition in healthy individuals. However, the acute cartilage
biomarker response was similar between the two physical activity
conditions even though the conditions differed in magnitude and
frequency of loading. Further work is needed to better understand how
to optimize joint loading in people at risk for knee OA to maintain
cartilage health.
Harkey MS, Blackburn JT, Hackney AC, Lewek M, Schmitz R,
Pietrosimone B. Sex-Specific Associations Between Cartilage Structure
and Metabolism at Rest and Acutely Following Walking and Drop-Landing.
Accepted for Publication in
Cartilage. 2020 Aug
Lane AR, Harkey MS , Davis
HC, Luc-Harkey BA, Stanley L, Hackney AC, Blackburn JT, Pietrosimone B.
Body Mass Index and Type 2 Collagen Turnover in Individuals after
Anterior Cruciate Ligament Reconstruction. Published in Journal of Athletic Training.
2019 Mar; 54(3):270-275. PMID: 30829538. PMCID: PMC6485853.
Harkey
MS , Blackburn JT, Hackney AC, Lewek M, Schmitz R,
Pietrosimone B. Acute Serum Cartilage Biomarker Response following
Walking and Drop Landing. Published in Medicine & Science in
Sports & Exercise. 2018 July, 50(7):1465-71. PMID:
29470279.
Harkey MS,
Luc B, Golightly Y, Thomas A, Driban J, Hackney A, Pietrosimone B.
Osteoarthritis-Related Biomarkers Following Anterior Cruciate Ligament
Injury and Reconstruction: A Systematic Review. Published in
Osteoarthritis and Cartilage. 2015 Jan, 23(1):1-12. PMID: 25219671.
Compositional MRI sequences
(e.g., T1rho, T2
mapping) assess cartilage composition by quantifying proteoglycan
density or collagen orientation. We have used compositional sequence to
determine how cartilage composition is associated with walking
biomechanics, patient reported outcomes, and muscle strength in
individuals following knee injury. We have identified that specific
walking strategies and muscle weakness is associated with poor
cartilage composition. Additionally, poor cartilage composition is
related to poor patient reported outcomes following knee injury.
Therefore, interventions targeting the specific walking strategies and
improvement in strength may help improve cartilage composition and
patient outcomes following knee injury.
Pietrosimone B, Pfeiffer SJ, Harkey MS , Wallace
K, Hunt C, Blackburn JT, Schmitz R, Lalush D, Nissman D, Spang JT.
Quadriceps Weakness Associates with Greater T1ρ Relaxation Time in the
Medial Femoral Articular Cartilage 6 Months Following Anterior Cruciate
Ligament Reconstruction. Published in Knee Surgery, Sports
Traumatology, Arthroscopy.
2019 Aug; 27(8):2632-2642. PMID: 30560446.
Pfeiffer S, Spang J, Nissman D,
Lalush D, Wallace K, Harkey
MS , Stanley L, Schmitz R, Schwartz T, Blackburn JT,
Pietrosimone B. Gait Mechanics and T1rho MRI of Tibiofemoral Cartilage
6 Months Post ACL Reconstruction. Published in Medicine & Science in
Sports &
Exercise. 2019 Apr; 51(4):630-639. PMID: 30444797.
Pietrosimone B, Nissman D,
Blackburn JT, Harkey MS ,
Creighton A, Kamath G, Healy K, Schmitz R, Driban JB, Padua DA,
Marshall SW, Jordan JM, Spang JT. Associations between Cartilage
Proteoglycan Density and Patient Outcomes 12months Following Anterior
Cruciate Ligament Reconstruction. Published in Knee. 2018 Jan,
25(1):118-29, PMID:
29329888.