Ambulatory Monitoring of Knee Loading during ADL, towards Personalized Treatment and Rehabilitation Strategies for Knee Osteoarthritis Patients

Knee osteoarthritis (OA) is a common musculoskeletal condition, considered as
the 4th most degenerative disease in the world. Knee OA is the single most
common cause of pain and disability in middle-aged and older adults [1]: 25% of
people over 55 years have a persistent episode of knee pain, of whom about 1/6
consult their general practitioner in the Netherlands [2]. The exact etiology
of OA is yet to be established, but the main risk factors are well known and
commonly include mechanical, biochemical and genetic risk factors. Of these
risk factors, obesity is considered a prominent one. Obesity is associated with
altered knee kinematics and increased knee loading and systemic and hormonal
factors may accelerate the progression of OA [3-8].
Andriacchi and Mundermann (2008) proposed a common framework for the initiation
and progression of knee osteoarthritis in which the interplay between abnormal
biomechanics and changes in cartilage metabolism lead to degeneration. Studies
on ambulatory loads suggests that risk factors such as being obese, may
initiate the development of knee osteoarthritis, similar to that in ACL injury.
The cartilage thickness at the knee joint in overweight and obese subjects
responds to loading during gait in a manner similar to patients with
osteoarthritis. It is argued that increased weight initiates cartilage
degeneration prior to the emergence of osteoarthritis symptoms. Unraveling the
interactions between obesity, in vivo function, joint anatomy, and cartilage
mechanobiology requires combined evaluation of biological changes (biomarkers),
structural adaptation (quantitative MRI), and in vivo patient function (gait
analysis).

The pathomechanics of OA should be studied in the context of interacting
abnormal, excessive and repetitive loading patterns of the knee joint, which
are highly dependent on the daily activity patterns. In addition, OA patients
show adaptive locomotion that can be used to identify progression of OA [9]. A
smart knee brace was recently developed within the Biosensing project to
quantify peak loads and repetitive loading patterns of the knee joint during
ADL. This novel technology will enable to tailor treatment and rehabilitation
strategies to the needs of the individual patient.

Previous studies [10] have proposed that cartilage degeneration due to obesity
could be caused by changes in the joint kinematics during ADL that shifts the
loading applied to cartilage. Such a shift may cause regions of cartilage to
become newly (excessively) loaded, be subjected to altered levels of
compression and tension, or become unloaded. The metabolic sensitivity of
chondrocytes to such changes in their mechanical environment, combined with the
low adaptation potential of mature cartilage, could lead to cartilage
degeneration and premature osteoarthritis in obesity [11-14]. Hence, obesity
may be used as a model to understand the relationship between mechanics and
biology, as well as helping to explain the importance of restoring normal
ambulatory kinematics in obese subjects to avoid premature osteoarthritis.

The main questions for this study are;
* Does obesity lead to detrimental kinematics and subsequent load shifts across
the articular surface of the knee during daily activity?
* Does obesity affect the biological response to loading measured from
biomarkers for cartilage degeneration?
* What kind of compensatory strategies do obese OA patients employ during daily
activity/exercise to unload the knee?

The study will be a cross-sectional study in which three groups will be
included. The three groups will consist of an obese (BMI>30) OA group, a
non-obese (BMI<25) OA group, and a healthy control group. Groups will be
matched for age and gender. All tests are performed only once , in order to
compare the three groups to each other on lower limb mechanics (i.e. mechanics
regarding the knee joint), cartilage adaptation (i.e. cartilage degeneration)
and biological adaptation (i.e. biomarker levels in urine samples).

Subjects will be divided into 3 groups depending on BMI (BMI<25 which is the
non-obese group or BMI>30, which is the obese group), and a healthy control
group.
This creates three groups:
1. Obese (BMI>30) with knee osteoarthritis (according to the American College
of rheumatology classification criteria).
2. Non-obese (BMI<25) with knee osteoarthritis
3. Healthy control group (BMI<25 and no knee osteoarthritis and or other
diseases according to the exclusion criteria).
In addition, there will be no blinding. The researchers do know in which group
the subjects belong and the subject will know to which group they will be
assigned.

The measurements will take place on two different locations (the movement
laboratory of the department of Human Movement Sciences of the University of
Maastricht and the department of Radiology at the University Hospital of
Maastricht). Subjects will be measured in one day according to the time
schedule mentioned above. First the subjects will be measured in the Motion
laboratory of the department of Human Movement Sciences at the University of
Maastricht. Before starting the tests, subjects are asked to turn in their
urine samples (i.e. first urine of the day and midstream) that they collected
themselves in the morning in a previously send urine jar. These are processed
in our laboratory of the department of Orthopedic Surgery and frozen for
further analysis. Thereafter, maximal isometric and dynamic knee extensor and
knee flexor strength will be measured by use of a Biodex dynamometer in the
Motion Laboratory. Furthermore a 3D-motion-analysis is performed in combination
with EMG measurements using a wireless 8-channel EMG recording unit.
Hereafter, a MRI scan will take place at the radiology department in the
University Hospital Maastricht. Subjects are guided by one of the researchers.
After all the measurements are performed subjects return home with a smart knee
brace for a day (i.e. 8 hours) of ambulatory datarecording. Besides the
kneebrace a CAM activity monitor is used in this study. The CAM will measure
activity in daily life for 7 days in a row. Subjects will receive all
information of both ambulant systems at the end of the measurements in the
laboratory of human movement sciences. The knee brace and CAM activity monitor
is picked up again by one of the researchers after the measurement period for
data-analysis.

Subjects will be tested in the Motion Laboratory through the Biodex system
requiring them to maximally apply force in an isometric setting. These tests
have been widely accepted as applicable when testing MVC. The risks involved
are minimal and could be some muscle soreness the next few days. No other risks
are involved or otherwise described in other studies. Next 3D-motion analysis
is performed, which requires preferred walking speed, getting up from a chair
en walking a one step stairs with side-bars. The entire walking surface is
flat, the room is fully lighted and a research-assistant will help the subjects
in performing the tests at all times. Otherwise there are no risks involved.
EMG measurement only requires shaving of the skin if necessary. We ask about
allergies before applying the stickers and using chloorhexidine. There are no
risks involved in EMG measurement. Next a MRI scan is performed. This requires
lying down very still from a subject for about an hour. The Radiology
department will assist in preparing the subject and explaining the protocol.
All metal objects are removed from the subject. The potential risks involved
could be previously not mentioned claustrophobia. If this ought to be an acute
problem to the subject, then subjects as well as the MRI-performing
radiology-assistant are allowed to withdraw from testing at all times!
Otherwise we conclude there are no other risks involved.
The ambulatory knee brace does not include any risks. It is a closed system,
fitted upon a registered NEA *Push*-brace, which can be worn only in one way
and is recharged by the common 220V in Dutch homes. The CAM activity monitor
does not involve any risk, subjects will be informated about the placement of
the CAM.