Rheumatoid Arthritis and Osteosarcopenia: Associated Factors

Our study is a cross-sectional study, and its aim is to compare and analyze the prevalence of sarcopenia and osteoporosis in patients with rheumatoid arthritis (RA) with a control group and to reveal the impact of sarcopenia on osteoporosis, fall risk, and fracture risk. This prospective cross-sectional study will include 100 rheumatoid arthritis patients and 100 healthy controls, matched for age and sex. Patients will be consecutively and meticulously enrolled based on inclusion and exclusion criteria.

A detailed medical history and examination will be performed on the patients, and their clinical and sociodemographic characteristics will be recorded. Blood tests for RA (RF, Anti-Cyclic Citrullinated Peptide (anti-CCP), CRP, ESR) and disease activity levels (DAS28) will be recorded. The prevalence of osteosarcopenia will be assessed in both the RA and healthy control groups.These groups will be evaluated using various scales and tests (including power, performance tests) including musculoskeletal ultrasonographic measurements and clinical functional assessment tests. he sarcopenic group will be categorized based on the level of sarcopenia, according to the new ISarcoPRM criteria (non-sarcopenic, dynapenic, sarcopenic, and severe sarcopenic). Osteosarcopenia will be evaluated for both groups, and the collected data will be analyzed with primary and secondary outcomes. The analysis will explore the potential relationships between rheumatoid inflammation, sarcopenia, and osteoporosis.

Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease that affects 5 out of 1,000 adults worldwide. The disease affects women 2 to 3 times more frequently than men and can occur at any age. The most common period for its onset is typically in the sixth decade (late 50s to 60s). In patients with rheumatoid arthritis, sarcopenia and osteopenia-osteoporosis are two commonly observed clinical conditions. Osteoporosis has been reported to be approximately twice as common in RA patients compared to the general population. The prevalence of osteoporosis in RA patients ranges from 6.3% to 36.3% in the hip region and from 12.3% to 38.9% in the spine region. Additionally, the prevalence of sarcopenia in RA patients is 21%.

Osteopenia/osteoporosis and sarcopenia are two commonly observed conditions in patients with rheumatoid arthritis (RA). Various factors increase the risk of sarcopenia in RA. These include reduced physical activity, increased levels of TNF-α and IL-1β, elevated energy expenditure at rest, increased CRP levels, and secondary immobility resulting from joint pain and stiffness.

Chronic inflammation in rheumatoid arthritis (RA) is known to increase osteoclast differentiation and suppress the osteogenesis process. In RA patients, the presence of antibodies against OPG, which inhibits RANKL, has been detected. Additionally, levels of Dickkopf-related protein 1 (DKK-1), which inhibits the Wnt signaling pathway, have been shown to be higher in the serum of RA patients compared to healthy controls. The prevalence of osteoporosis in rheumatoid arthritis patients has been reported to be more than twice that of the general population. For these reasons, the detection and prevention of osteosarcopenia in patients with rheumatoid arthritis should be considered an important comorbidity.

Sarcopenia is a syndrome characterized by the progressive and general loss of skeletal muscle mass and strength, carrying the risk of negative outcomes such as physical disability, low quality of life, and death. Although sarcopenia is typically associated with elderly individuals, it can also occur in younger individuals due to various diseases or conditions. Since its prevalence is higher in older adults compared to other age groups, it can also be referred to as a geriatric syndrome.

Various imaging methods such as computed tomography (CT), magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DXA), bioimpedance analysis, and ultrasound can be used to determine muscle mass in the diagnosis of sarcopenia.

Osteoporosis is a systemic skeletal disease characterized by a decrease in bone mass and a deterioration of the structural integrity of bone tissue, which increases bone fragility and creates a risk of fractures. The World Health Organization (WHO) defines osteoporosis through measurements made using dual-energy X-ray absorptiometry (DXA). According to this definition, the T-score in the lumbar spine, femoral neck, or distal third of the radius is evaluated as follows: T-score ≥ -1.0 is normal, between -1.0 and -2.5 is osteopenia, and T-score ≤ -2.5 is considered osteoporosis. Additionally, if the T-score is below -2.5 and one or more osteoporotic fractures are present, this condition is referred to as established osteoporosis.

Sarcopenia is evaluated based on specific criteria. Although the information may change over time, it is important to consider muscle strength, muscle mass, and physical performance when diagnosing sarcopenia today.

Recently, the STAR study has been published, emphasizing the importance of regional muscle mass measurements in the diagnosis of sarcopenia. The study showed that the thickness of the anterior thigh muscle is the parameter that decreases the most with aging, and this measurement has a stronger correlation with height and BMI. In this regard, it is recommended to use the STAR value, obtained by dividing the anterior thigh muscle thickness measured by ultrasound by BMI, in the diagnosis of sarcopenia. The STAR threshold value has been set as \<1.0 for women and \<1.4 for men.

The formula is:

STAR = Anterior thigh muscle thickness (mm) / Body Mass Index (BMI) (kg/m²)

International Society of Physical and Rehabilitation Medicine, ISPRM (2021) has published a new sarcopenia diagnostic algorithm, which also includes the STAR study and ISarcoPRM recommends screening for all older adults and adults with RAS-associated disorders.

ISarcoPRM has set cut-off values of ≥12 seconds for the sit-to-stand test and \<32 kg for grip strength in men and \<19 kg in women to identify low muscle function. Initially, both tests are recommended. If low values are detected in either of these tests, the patient is considered to have "probable sarcopenia."

In individuals diagnosed with probable sarcopenia, it is recommended to measure the anterior thigh muscle thickness using ultrasound and calculate the STAR value. If the STAR value is below the threshold level determined by gender, the individual is classified as having "sarcopenia." Additionally, if the walking speed is ≤ 0.8 m/s and/or the individual cannot rise from a chair without support, this condition is defined as "severe sarcopenia."

If at least one of the patient's muscle function tests is low but the STAR value is normal, the patient is considered to have "dynapenia.

In our study, in addition to anterior thigh thickness, Achilles tendon thickness will also be measured. There is insufficient research explaining the relationship between Achilles tendon thickness and sarcopenia or osteoporosis. In this study, we will also investigate whether there is a relationship between Achilles tendon thickness and sarcopenia and/or osteoporosis.

There are few studies examining the relationship between RA, osteoporosis, and sarcopenia with heterogeneous methodologie. Therefore, the aim of this study is to evaluate the prevalence of osteosarcopenia in RA patients and control groups, and to investigate the impact of sarcopenia, along with the effects of inflammation, on osteoporosis, fall, and fracture risk. By evaluating sarcopenia according to the ISarcoPRM criteria, the study aims to address the gap in the literature with a unique and robust original methodologies.

Eligibility Criteria:
Inclusion criteria:

1. Being diagnosed with RA according to the ACR/EULAR 2010 criteria
2. Being a female or male over the age of 50
3. Having the mental and physical capacity to complete the study questionnaires and tests
4. Providing voluntary consent to participate in the study by signing the Informed Consent Form

Exclusion Criteria:

1. Having an acute illness/disability or significant cognitive impairment that prevents understanding and performing the required tests
2. Having thyroid or parathyroid disease, uncontrolled diabetes, Cushing's syndrome, anemia.
3. History of malignancy
4. Severe cardiovascular disease, enal failure, advanced-stage COPD, decompensated liver disease
5. History of gastrointestinal (GIS) surgery

7-Having another coexisting autoimmune/inflammatory rheumatic disease (e.g., SLE, Ankylosing Spondylitis, etc.), psoriatic arthritis, vasculitis, familial Mediterranean fever...)

8-Having severe/symptomatic hand osteoarthritis and/or deformities

9-Severe/symptomatic osteoarthritis in the knee, lumbar, hip, or ankle region

10-Having Carpal Tunnel Syndrome, De Quervain, lateral epicondylitis, cubital tunnel syndrome or a history of traumatic hand injury

11-Having a significant neurological disease, stroke, MS, myopathy, Parkinson's disease, radiculopathy/polyneuropathy/brachial plexopathy or others nerve root compressions

12-History of surgical intervention on the upper and lower extremities or spine

13-Having severe kyphosis or scoliosis

14-Having any others disease causing balance disorders (neurological, orthopedic, metabolic, etc.)

15-Having a major/significant psychiatric disorder (based on the medical history, and hospital records)

16-Current use of androgens or estrogens

17-Having prostheses, being fully dependent, or immobilized