Clinical trial NCT06173193: Effects of Multicomponent Exercise on Subchondral Bone and Cartilage in Postmenopausal Women with Knee Osteoarthritis
Official title: Effects of a Multicomponent Exercise Regimen on Subchondral Bone, Cartilage, and Inflammation Markers in Postmenopausal Women with Knee Osteoarthritis: a Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Osteoarthritis, Knee
Keywords: Exercise
Subchondral bone
Cartilage
Randomized controlled trial
Postmenopausal women
Osteoarthritis
Physiotherapy
Joint Diseases
Musculoskeletal Diseases
Physical functioning
Lead sponsor: University of Jyvaskyla
Sponsor class: OTHER
Collaborators: name: University of Oulu
name: Wellbeing Services County of Central Finland
name: UKK Institute
name: Research Council of Finland
First posted: 2023-12-15
Enrollment: 100
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Today, osteoarthritis (OA) is considered a whole-organ disease that is amenable to prevention and treatment in the early stages. Information on the articular cartilage and subchondral bone responses to exercise may help to develop safe and feasible exercise programs which can potentially improve cartilage and bone properties. Therefore, the goal of this study is to produce the knowledge needed to understand what effects multicomponent exercise regimen have on subchondral bone and articular cartilage of the knee joint in postmenopausal women with knee OA.

Participants will be randomized into either:

1. Intervention group, which conducts multicomponent exercise regimen including alternating step-aerobic and resistance training.
2. Reference group, which represents the standard rehabilitative management for knee OA patients with home exercises.

Researchers will compare intervention and reference groups to see if subchondral bone morphology and properties and cartilage biochemical alterations differ between the groups at the end of the 8-month intervention and 12-month follow-up period.

Detailed description: The study is an 8-month, randomized controlled intervention study with 12-month follow-up in volunteer postmenopausal (55-75-year-old) women with mild radiographic knee OA according to the Kellgren-Lawrence classification (grade 1-2). The participants will be randomly assigned into the subgroups. The study will be conducted in two phases.

8-month multicomponent exercise regimen will be carried out gradually and progressively three times a week by experienced and recently trained exercise instructors. The instructors will keep an attendance and an adverse event record for each of the intervention group's participants. The home exercises carried out three times a week by the reference group represent the standard rehabilitative management for knee OA patients.

In addition to the above-mentioned treatments, all participants will receive instructions to use paracetamol on an as-needed basis. Participants will be called to end-point measurements at 8 months after baseline and follow-up measurements at 20 months after baseline.

The overall goal of this study is to produce the knowledge needed to understand what effects multicomponent exercise regimen have on subchondral bone and articular cartilage of the knee joint in postmenopausal women with knee OA. In addition, the aim is to develop means to improve functional competence as well as to prevent physical disability among women suffering from knee OA. Specifically, the objectives are to investigate the effects of joint loading exercise regimen on knee joint subchondral bone morphology and properties, and cartilage biochemical alterations and their 12 month maintenance in women with knee OA. Also, training effects on molecular biomarkers related to OA and inflammation, bone traits, physical function, performance, body composition, and clinically important symptoms will be examined.

Eligibility criteria: Inclusion Criteria:

* voluntary women 55-75 years of age.
* no history of any illness for which exercise is contraindicated or that would limit participation in the exercise program.
* knee pain during the last 12 months.
* willingness and voluntarily signed informed consent to undergo testing and intervention procedures with all of its aspects.
* weight-bearing knee x-rays show radiographic Kellgren-Lawrence grade 1-2 OA in one or both tibiofemoral joints.

Exclusion Criteria:

* body-mass index over 35 kg/m2.
* knee instability or trauma that would jeopardize the training.
* inflammatory joint disease.
* intra-articular steroid injections in the preceding 12 months in the knee.

Primary outcomes:
measure: Tibiofemoral articular cartilage's glycosaminoglycan content
timeFrame: Baseline, 8 months, 20 months
measure: Tibiofemoral articular cartilage's collagen content and orientation
timeFrame: Baseline, 8 months, 20 months
measure: Tibiofemoral articular cartilage thickness (mm)
timeFrame: Baseline, 8 months, 20 months
measure: Tibiofemoral articular cartilage volume (mm^3)
timeFrame: Baseline, 8 months, 20 months
measure: Tibiofemoral subchondral bone mineral density (g/cm^3)
timeFrame: Baseline, 8 months, 20 months
measure: Tibiofemoral subchondral bone mineral content (g)
timeFrame: Baseline, 8 months, 20 months
measure: Tibiofemoral joint space narrowing (mm)
timeFrame: Baseline, 8 months, 20 months
Secondary outcomes:
measure: Bone mineral content (BMC, g) of the femoral neck
timeFrame: Baseline, 8 months, 20 months
measure: Areal bone mineral density (aBMD, g/cm^2) of the femoral neck
timeFrame: Baseline, 8 months, 20 months
measure: Cortical thickness (mm) of the femoral neck
timeFrame: Baseline, 8 months, 20 months
measure: Femoral neck width (mm)
timeFrame: Baseline, 8 months, 20 months
measure: Cross-sectional area (cm^2) of the femoral neck
timeFrame: Baseline, 8 months, 20 months
measure: Cross-sectional moment of inertia (cm^4) of the femoral neck
timeFrame: Baseline, 8 months, 20 months
measure: Section modulus (cm^3) of the femoral neck
timeFrame: Baseline, 8 months, 20 months
measure: Total body fat percentage (%)
timeFrame: Baseline, 8 months, 20 months
measure: Fat Free Mass Index (FFMI, kg/m^2)
timeFrame: Baseline, 8 months, 20 months
measure: Clinically important OA-symptoms and physical function
timeFrame: Baseline, 8 months, 20 months
measure: Health-related quality of life
timeFrame: Baseline, 8 months, 20 months
measure: Work disablement
timeFrame: Baseline, 8 months, 20 months
measure: Self-rated physical activity
timeFrame: IPAQ: Baseline, 8 months, 20 months. Physical activity diary: through the 8-month study intervention in the control group
measure: Objective daily physical activity
timeFrame: See above
measure: Quantity of painkillers consumed
timeFrame: Through the 8-month study intervention
measure: Systemic inflammation markers
timeFrame: Baseline, 8 months, 20 months
measure: Metabolic profile
timeFrame: Baseline, 8 months, 20 months
measure: Cardiorespiratory fitness
timeFrame: Baseline, 8 months, 20 months
measure: Knee extension and flexion maximal isometric muscle strength
timeFrame: Baseline, 8 months, 20 months
measure: Static balance
timeFrame: Baseline, 8 months, 20 months
measure: 30 second chair-stand test (seconds)
timeFrame: Baseline, 8 months, 20 months
measure: Timed up and go (TUG) (seconds)
timeFrame: Baseline, 8 months, 20 months
measure: 40m Fast-paced walk test (seconds)
timeFrame: Baseline, 8 months, 20 months
measure: Stair climb test (seconds)
timeFrame: Baseline, 8 months, 20 months
measure: Walking biomechanics
timeFrame: Baseline, 8 months, 20 months
Other outcomes:
Locations:
city: Jyväskylä
country: Finland
facility: University of Jyväskylä
Study officials:
affiliation: University of Jyvaskyla
name: Ari Heinonen, Prof., emeritus
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dobson F, Hinman RS, Roos EM, Abbott JH, Stratford P, Davis AM, Buchbinder R, Snyder-Mackler L, Henrotin Y, Thumboo J, Hansen P, Bennell KL. OARSI recommended performance-based tests to assess physical function in people diagnosed with hip or knee osteoarthritis. Osteoarthritis Cartilage. 2013 Aug;21(8):1042-52. doi: 10.1016/j.joca.2013.05.002. Epub 2013 May 13.