OA Pearl 1

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.

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 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 and give more information about this study.

Individuals 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 one or both hips at the research center. During this visit, a physical examination of one or 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 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 another Patient Information Folder. Individuals will be asked to carefully read all information and sign informed consent if they are willing to participate. 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 in case they want to participate in the proposed preventive program.

Not applicable.

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 those who are eligible:
- time spend to complete the additional questionnaire
- time spend to undergo the 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.