Effect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study

C4M hypothesizes that patients with low muscle strength may respond differently to different types of exercise intervention, dependent on the underlying aetiology, i.e. impaired protein synthesis versus metabolic dysfunction and that this response is predictable based on the clinical diagnosis, i.e. rheumatoid arthritis (RA), osteoarthritis (OA) and Sarcopenia alone (SARC) and a number of clinical, blood based and muscle metabolic and architectural biomarkers. Understanding the underlying biochemical response of each patient group to the different type of exercise loading could help with the development of disease-specific training, making it more effective and more predictable on outcomes.

Rationale: C4M hypothesizes that patients with low muscle strength may respond differently to different types of exercise intervention, dependent on the underlying aetiology, i.e. impaired protein synthesis versus metabolic dysfunction and that this response is predictable based on the clinical diagnosis, i.e. rheumatoid arthritis (RA), osteoarthritis (OA) and Sarcopenia alone (SARC) and a number of clinical, blood based and muscle metabolic and architectural biomarkers. Understanding the underlying biochemical response of each patient group to the different type of exercise loading could help with the development of disease-specific training, making it more effective and more predictable on outcomes.

Objective: to explore effectivity, interaction and predictability of two types of exercise intervention in patients with RA, OA and SARC alone. The primary outcome of this study will be isokinetic muscle strength of the quadriceps in all three target groups.

Study design: two-arm parallel-group exploratory trial including a total of 69 patients: study population 23 patients with OA, 23 patients with RA and 23 patients with SARC alone (according to the revised European Working Group on Sarcopenia in Older People consensus definition (EWGSOP-II criteria, Cruz- Jentoft 2019).

Intervention: Exercise intervention for 3 times a week for 8 weeks.

Main study parameters/endpoints: the main study parameter is the difference in isokinetic muscle strength pre- and post-intervention in all three patient groups. The secondary study parameters include muscle endurance; mitochondrial respiration, gene and protein expression and histology via muscle biopsies; inflammation via bloodwork and feasibility.

Intervention: Exercise intervention for 3 times a week for 8 weeks.

Main study parameters/endpoints: the main study parameter is the difference in isokinetic muscle strength pre- and post-intervention in all three patient groups. The secondary study parameters include muscle endurance; mitochondrial respiration, gene and protein expression and histology via muscle biopsies; inflammation via bloodwork and feasibility.

Eligibility Criteria:
Inclusion Criteria For all patients

* Low muscle strength defined as hand grip strength (HGS) \&amp;lt;27 kg and \&amp;lt;16 kg for males and females respectively. If HGS is not possible due to interfering pain or joint- deformity, the chair stand test is used instead, with low muscle strength defined as not able to rise from the chair without arms or a time \&amp;gt;15 sec (Cruz Jentoft 2019).
* Gait speed of \&amp;gt;0.8m/s to exclude patients who are too disabled to participate in the study (Cruz Jentoft 2019).

OA patients

* Age between 50 and 70
* Patients with either knee and/or hip OA according to clinical American College of Rheumatology (ACR) criteria (Altman 1986).
* Kellgren and Lawrence grading score of 2-4 for hip and/or knee OA (Altman 1991).
* C-reactive Protein (CRP) levels \&amp;lt;10mg/L within 3 months prior to enrolment (Sanchez 2014).

Rheumatoid arthritis patients

* Age between 50 and 70
* Diagnosed with RA according to European Alliance of Associations for Rheumatology (EULAR)/ACR criteria (Aletaha 2010).
* Disease activity score in 28 joints (DAS28) 2.8\&amp;lt;5.6, as defined by the EULAR criteria (Aletaha 2010), either de novo or despite Disease-Modifying Antirheumatic Drug therapy.
* Stable disease three months prior to the start of the exercise intervention.
* Stable rheumatic medication three months prior to the start of the exercise intervention.
* Stopped the usage of corticosteroids 3 months prior to the start of the exercise intervention.
* Disease duration \&amp;gt;1 year and \&amp;lt;15 years

Sarcopenia patients

* Age between 50 and 80.
* Sarcopenia without joint involvement (no OA, RA), according to the EWGSOPII criteria (Cruz Jentoft 2019) of low muscle strength defined as HGS \&amp;lt;27kg and \&amp;lt;16 kg for males and females respectively (dynapenia). This group will therefore primarily involve participants with probable sarcopenia (dynapenia) but may also encompass participants with confirmed sarcopenia (appendicular muscle Lean Mass (ALM)/height2 \&amp;lt;7.0 kg/m2 for males and \&amp;lt;5.5 kg/m2 for females) as this is not a selection criterion. Severe sarcopenia will be excluded (gait speed \&amp;lt;0,8 m/s).
* Exclude patients with joint complaints (RA, OA, or other joint disease).

Exclusion Criteria:

* Body mass index (BMI) \&amp;lt; 18 and \&amp;gt; 35 Kg/m2
* Contra-indications for exercise testing and prescription as indicated by the ACSM guideline (i.e. progressive increase in heart failure symptoms, myocardial infarction less than three months before the start of the training programme, severe cardiac ischemia upon exertion, respiratory frequency of more than 30 breaths per minute and heart rate at rest \&amp;gt;110 beats per minute).
* Participants taking beta-blockers for the duration of the intervention.
* Diagnosed with other neurologic or cachectic diseases or major surgery that may interfere with muscle quality (i.e. multiple sclerosis, ongoing cancer treatment or radiotherapy/ chemotherapy in the previous 6 months).
* Participating in another regular and intense (i.e. high physical loading training such as high-load circuit training for muscle gain and fat loss \&amp;gt; 2 times a week) physical training programme within 2 months prior to enrolment.
* Ligament/muscle tear and/or other injuries within 6 months.
* Taking drugs (e.g. performance enhancing drugs) or nutritional supplements (e.g. protein powder) known to increase muscle mass.
* Inability to be scheduled for exercise therapy
* Insufficient comprehension of Dutch language or no informed consent.