Towards the primary prevention of hip OA - pilot study

Osteoarthritis (OA) is already one of the most common and by far the fastest
growing disease in the Netherlands. Despite the enormous severity of the
symptoms of osteoarthritis, we can only offer patients with osteoarthritis
modestly effective treatments for their complaints.

Treatments to cure osteoarthritis have not yet been very successful, but have
mainly been investigated in patients where the joint tissue is already
significantly damaged and hardly specific to the type of osteoarthritis.
With such a common, disabling and incurable condition, our efforts should be
much more focused on its primary prevention.

The hip is the second most commonly affected joint (after the knee) and is
responsible for the highest rate of disability. Several modifiable risk
factors, mainly related to hip shape, have been previously identified and
therefore have great potential for preventive options.

With our future preventive hip OA trial we will assess the effects of exercise
therapy in individuals at high-risk for hip OA development due to the presence
of cam morphology. An important outcome measure in the future preventive trial
will be the progression of structural abnormalities on MR images, such as bone
marrow lesions, cartilage defects, labral tears, osteophytes, and inflammation.

The theoretic basis of primary prevention of hip OA might sound simple,
appealing, and feasible: preventing the onset of OA among subjects without, but
at high risk for OA. Nevertheless, to realize this, there are many challenges.

Two challenges will be studied in this pilot study.

Challenge #1; Identify treatment goals
We have previously shown that hip morphology (e.g. a cam deviation) is one of
the largest risk factors for the development of hip osteoarthritis.
Therefore, preventing the development of osteoarthritis in individuals with
morphological risk factors appears to be a promising strategy.

One of the major risk factors for cam morphology is sport participation during
the last growth spurt.
Especially for sport participation in high loading sports, such as soccer,
basketball, hockey, and jumping sports.
Traditionally, these sports were male dominant sports and hence reports of cam
prevalence showed higher prevalence among men. However, given the increase in
sport participation in girls over the last decades, increasing prevalence is
reported in women as well.

Challenge #2; Designing the intervention
When a reliable individualized estimation of hip OA risk can be made, high risk
subpopulations can be identified, which probably increases the likelihood of
adherence to a certain preventive strategy.

Interestingly, a small recent RCT showed a significant increase in cartilage
quality and clinically relevant effects on hip joint symptoms after a
conservative physiotherapist-led hip therapy program among patients with cam
morphology .

Given these results and the knowledge on the high risk of hip OA development in
individuals with cam morphology, we have identified the potential treatment
population and a potential intervention for our future preventive hip OA trial.

Challenge #3; Measuring the effect
Both OA symptoms and structural features of OA develop gradually. Therefore,
when evaluating potential outcomes for preventive trials in OA, the annual
incidence rate of the outcome is an important feature for the feasibility of
such a trial.

The primary objective of the current pilot study will be to assess the
feasibility of participant selection methods to identify individuals with cam
morphology free of hip OA.

Secondary objectives include
a) the evaluation of the willingness of potential participants to participate
in a preventive trial and to undergo the intervention, and

b) to gain insight into structural features of early stages of hip OA on MRI of
potential participants, to design relevant outcome measures.

Study design

The current study will be an observational feasibility pilot. For recruitment,
we will compare three strategies:

#1) Recruitment through GP practices.
We will recruit three GP practices from our regional network in the greater
Rotterdam region. Within these practices, all registered patients aged 18-55
years without a diagnosis of hip OA will be sent an information letter.
Those who report participation in high loading sports when aged 10 through 16
for >=2 days/week for >=1 year and are interested to participate will be asked to
contact the research center.

In addition, we will post advertisements in local media in the Rotterdam area
(strategy #2), such as De Havenloods, AD Rotterdam, RTV Rijnmond, but also
through the social media channels of Erasmus MC and our Department.
The advertisement will call for individuals who participated in high loading
sports when aged 10 through 16 for >=2 days/week for >=1 year and who are
interested to join our research on OA prevention, to reach out to the research
center.

For recruitment strategy #3, we will collaborate with our stakeholders at
national sport associations within our network (e.g., Golazo Sport (running),
National Hiking Association, and KNLTB (tennis)). As done in previous
collaborations, these associations will reach out to their members in the
Rotterdam area and ask them to spread our advertisement (see strategy #2) with
their supporters. As for strategy #2, individuals interested to join the study
are asked to contact the research center.

With all individuals that contact the research center, we will perform a
telephonic screening to ascertain the absence of clinical hip OA (using NICE
criteria; age >=45 years and activity-related hip joint pain and no or <=30
minutes of morning stiffness in the hip joint), the fulfilment of the inclusion
criteria, and through which means they were informed about this study.

Individuals without clinical hip OA, that do fulfil our recruitment criteria
will be invited
a) to complete an online questionnaire (±15 minutes) to obtain subjects*
characteristics, detailed sport participation during childhood, current hip
symptoms and functional limitations, and other risk factors for cam
morphology/hip OA (e.g., occupational loading) and

b) for a physical examination (±20 minutes) and radiography of their hips at
the research center.
During this visit, a physical examination of both hip joints will take place.
By subsequently obtaining radiography of all potential candidates, we will be
able to evaluate the efficiency of our recruitment strategies, regarding the
presence of cam morphology and the absence of any radiographic hip OA (i.e.
KL-grade=0).

After completion of the physical examination and radiographic assessment,
individuals with cam and no radiographic hip osteoarthritis in >=1 hip will
receive information material on the design of the future preventive RCT, along
with a Patient Information Folder. Individuals will be asked to carefully read
all information and sign informed consent if they are willing to undergo an MRI
and participate in a future preventive trial. After signing informed consent,
participants will receive the online questionnaire (approximately 5 minutes, in
which we assess their attitudes and beliefs regarding their willingness to
follow a preventive exercise therapy program), and they will be invited for a
multi-sequential MRI of the hip.

The burden to participants will equal
- the time spend to complete the online questionnaire,
- to travel to the research center,
- to undergo physical examination, and for completing the radiography

for subjects forfilling requirements{
- time to spend to complete the additioal questionnaire
- MRI (for those eligible for MRI).

Risks for participation are limited to the <0.1 mSv radiation dose for two hip
radiographs.

There is no direct benefit of participation, but with participating in this
pilot study, participants contribute to an important step in osteoarthritis
prevention science.