Rheumatoid Arthritis and Osteosarcopenia: Associated Factors

Official title

The Frequency of Osteosarcopenia in Patients With Rheumatoid Arthritis and the Factors Affecting the Sarcopenia-osteoporosis Relationship

Overview

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.

Detailed description

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.

Interventions

• Diagnostic test Osteosarcopenia in Patients with Rheumatoid Arthritis
  The prevalence of osteosarcopenia will be examined in this group. Sarcopenia will be categorized into 4 groups. Both the prevalence of osteosarcopenia and the subgroups of sarcopenia will be compared with the healthy control group. Through this comparison, we will explain the relationship between sarcopenia and osteoporosis, the factors affecting this relationship, and the changes in fall and fracture risk using various questionnaires and tests.
• Diagnostic test Osteosarcopenia in Healthy Control Group
  The prevalence of osteosarcopenia will be examined in this group. Sarcopenia will be categorized into 4 groups. The relationship between sarcopenia and osteoporosis, the factors affecting this relationship, and the risk of falls and fractures will be evaluated using various questionnaires and tests.

Primary outcome measures

• Sarcopenia assessment [Time frame: baseline]
• Osteoporosis assessment/dual-energy X-ray absorptiometry [Time frame: baseline]
• Balance and Gait Assessment Scale [Time frame: baseline]

Secondary outcome measures (8)

• Fracture Risk Assessment Tool (FRAX) [Time frame: baseline]
• Health Assessment Questionnaire, HAQ [Time frame: baseline]
• Handgrip Strength Test [Time frame: baseline]
• chair rise test [Time frame: baseline]
• Anterior Thigh Muscle Thickness Measurement [Time frame: baseline]
• 6-meter Walking Test [Time frame: baseline]
• Achilles tendon thickness measurement [Time frame: baseline]
• VAS pain (pain intensity) [Time frame: baseline]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Having an acute illness/disability or significant cognitive impairment that prevents understanding and performing the required tests
• Having thyroid or parathyroid disease, uncontrolled diabetes, Cushing's syndrome, anemia.
• History of malignancy
• Severe cardiovascular disease, enal failure, advanced-stage COPD, decompensated liver disease
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Ecologic or community

Study locations

Turkey (Türkiye) · 1 center

• Konya Beyhekim Training and Research Hospital Physical Medicine and Rehabilitation Clinic — Konya

Publications

• Kucukdeveci AA, Sahin H, Ataman S, Griffiths B, Tennant A. Issues in cross-cultural validity: example from the adaptation, reliability, and validity testing of a Turkish version of the Stanford Health Assessment Questionnaire. Arthritis Rheum. 2004 Feb 15;51(1):14-9. doi: 10.1002/art.20091. PMID 14872450
• Çifçili S, Ünalan PC. Yaşlılarda fonksiyonel kayıplara yaklaşım. Turkish Journal of Family Practice. 2004;8(4):166-73
• Ozcakar L, Kara M, Chang KV, Bayram Carli A, Hung CY, Tok F, Wu CH, Akkaya N, Hsiao MY, Tekin L, Wang TG, Ulasli AM, Chen WS, De Muynck M. EURO-MUSCULUS/USPRM. Basic Scanning Protocols for Ankle and foot. Eur J Phys Rehabil Med. 2015 Oct;51(5):647-53. Epub 2015 Sep 8. PMID 26351106
• Chiu YH, Liao CL, Chien YH, Wu CH, Ozcakar L. Sonographic evaluations of the skeletal muscles in patients with Pompe disease. Eur J Paediatr Neurol. 2023 Jan;42:22-27. doi: 10.1016/j.ejpn.2022.12.002. Epub 2022 Dec 6. PMID 36508847
• van Riel PL, Renskers L. The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. Clin Exp Rheumatol. 2016 Sep-Oct;34(5 Suppl 101):S40-S44. Epub 2016 Oct 18. PMID 27762189
• Pinheiro PA, Passos TD, Coqueiro Rda S, Fernandes MH, Barbosa AR. [Motor performance of the elderly in northeast Brazil: differences with age and sex]. Rev Esc Enferm USP. 2013 Feb;47(1):128-36. doi: 10.1590/s0080-62342013000100016. Portuguese. PMID 23515812
• Maggio M, Ceda GP, Ticinesi A, De Vita F, Gelmini G, Costantino C, Meschi T, Kressig RW, Cesari M, Fabi M, Lauretani F. Instrumental and Non-Instrumental Evaluation of 4-Meter Walking Speed in Older Individuals. PLoS One. 2016 Apr 14;11(4):e0153583. doi: 10.1371/journal.pone.0153583. eCollection 2016. PMID 27077744
• Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48( PMID 30312372

Identifiers

NCT: NCT06889415 · KBEAH-FTR-İK-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗