Effects of Multicomponent Exercise on Subchondral Bone and Cartilage in Postmenopausal Women With Knee Osteoarthritis

Osteoarthritis, Knee Clinical Trial

— LuRu2  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06173193
• Other study ID #: 21000057531
• Secondary ID: 351483
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2023
• Est. completion date: March 2026

Study information

• Verified date: December 2023
• Source: University of Jyvaskyla
• Contact: Ari Heinonen, Prof., emeritus
• Phone: +358408053551
• Email: ari.o.heinonen[@]jyu.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 55 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Behavioral:
• Multicomponent exercise regimen
A multicomponent exercise regimen applied is comprised of the step-aerobic and resistance training programs alternating every two weeks. The trainees participate in supervised training sessions 3 times a week for 8 months. Each session will include a 10-minutes warm-up, 30-minutes of effective training part and a 10-minutes period for cooling down. Step-aerobic: The program includes accelerating and decelerating through forwards and sideways movements with stops and turns to music. The degree of difficulty of movements and steps as well as training intensity will be gradually increased by increasing the height of the step benches. Resistance training: The participants will undergo a progressive resistance training program. Resistance training will emphasize training of following muscle groups: Quadriceps and hamstrings, hip abductors, adductors and extensors, and calf muscles. In addition to lower limb exercises, trunk and upper body exercises will be applied at intervals.
• Standard rehabilitative management
The treatments that will be provided to the members of a reference group represent the standard rehabilitative management for knee OA patients. The home exercises focus on functional exercises maintaining lower extremity flexibility and muscle function. The home exercises are instructed to be carried out three times a week, each work-out lasting 30 minutes.

Locations

Country	Name	City	State
Finland	University of Jyväskylä	Jyväskylä

Sponsors (5)

Lead Sponsor	Collaborator
University of Jyvaskyla	Research Council of Finland, UKK Institute, University of Oulu, Wellbeing Services County of Central Finland

Country where clinical trial is conducted

Finland, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tibiofemoral articular cartilage's glycosaminoglycan content	Assessed by quantitative Magnetic Resonance Imaging (qMRI) techniques at 3Tesla MR-system. Rotating frame of reference contrast adiabatic T1rho (ms) will be measured.	Baseline, 8 months, 20 months
Primary	Tibiofemoral articular cartilage's collagen content and orientation	T2 maps (ms) will be assessed by qMRI techniques at 3Tesla MR-system. In addition, some clinical MRI series will be conducted.	Baseline, 8 months, 20 months
Primary	Tibiofemoral articular cartilage thickness (mm)	Assessed by 3D-texture analysis.	Baseline, 8 months, 20 months
Primary	Tibiofemoral articular cartilage volume (mm^3)	Assessed by 3D-texture analysis.	Baseline, 8 months, 20 months
Primary	Tibiofemoral subchondral bone mineral density (g/cm^3)	Assessed by high-resolution cone beam computed tomography (CBCT).	Baseline, 8 months, 20 months
Primary	Tibiofemoral subchondral bone mineral content (g)	Assessed by high-resolution CBCT.	Baseline, 8 months, 20 months
Primary	Tibiofemoral joint space narrowing (mm)	Assessed by high-resolution CBCT.	Baseline, 8 months, 20 months
Secondary	Bone mineral content (BMC, g) of the femoral neck	Assessed by Dual-energy X-ray absorptiometry (DXA).	Baseline, 8 months, 20 months
Secondary	Areal bone mineral density (aBMD, g/cm^2) of the femoral neck	Assessed by DXA.	Baseline, 8 months, 20 months
Secondary	Cortical thickness (mm) of the femoral neck	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Secondary	Femoral neck width (mm)	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Secondary	Cross-sectional area (cm^2) of the femoral neck	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Secondary	Cross-sectional moment of inertia (cm^4) of the femoral neck	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Secondary	Section modulus (cm^3) of the femoral neck	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Secondary	Total body fat percentage (%)	Assessed by DXA.	Baseline, 8 months, 20 months
Secondary	Fat Free Mass Index (FFMI, kg/m^2)	Assessed by DXA.	Baseline, 8 months, 20 months
Secondary	Clinically important OA-symptoms and physical function	Assessed by Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire (Score 0-100). Higher scores represent better outcomes.	Baseline, 8 months, 20 months
Secondary	Health-related quality of life	Assessed by RAND 36-Item Health Survey questionnaire (Scores 0-100 on different domains). Higher scores represent a more favorable health state.	Baseline, 8 months, 20 months
Secondary	Work disablement	Assessed by short form of Örebro musculoskeletal pain screening questionnaire (Score 1-100). Higher scores estimate increased risk for future work disability.	Baseline, 8 months, 20 months
Secondary	Self-rated physical activity	Assessed by International Physical Activity Questionnaire (IPAQ, Metabolic equivalent task (MET) -minutes). Also, physical activity diary (MET-minutes) will be filled by the control group through the 8-month study intervention.	IPAQ: Baseline, 8 months, 20 months. Physical activity diary: through the 8-month study intervention in the control group
Secondary	Objective daily physical activity	Assessed by a tri-axial accelerometer (minutes & MET-hours), worn 24 hours a day. A tri-axial accelerometer will be used through the 8-month study intervention in the intervention group and periods of 7 consecutive days every two months during the 8-month study intervention in the control group. During the 12-month follow-up, all the participants will be measured every four months for seven consecutive days.	See above
Secondary	Quantity of painkillers consumed	Assessed by diary.	Through the 8-month study intervention
Secondary	Systemic inflammation markers	High sensitivity C-reactive protein and serum cytokines including interleukin-6 and tumor-necrosis factor alpha will be assessed from blood.	Baseline, 8 months, 20 months
Secondary	Metabolic profile	Circulating metabolomes including resistin, leptin, adiponectin, lipids, lipoproteins, and metabolites will be assessed from blood.	Baseline, 8 months, 20 months
Secondary	Cardiorespiratory fitness	Assessed by UKK 2km walk test (minutes and seconds).	Baseline, 8 months, 20 months
Secondary	Knee extension and flexion maximal isometric muscle strength	Assessed by an adjustable dynamometer chair (Newtons).	Baseline, 8 months, 20 months
Secondary	Static balance	Assessed by a single leg stance test (seconds).	Baseline, 8 months, 20 months
Secondary	30 second chair-stand test (seconds)		Baseline, 8 months, 20 months
Secondary	Timed up and go (TUG) (seconds)		Baseline, 8 months, 20 months
Secondary	40m Fast-paced walk test (seconds)		Baseline, 8 months, 20 months
Secondary	Stair climb test (seconds)		Baseline, 8 months, 20 months
Secondary	Walking biomechanics	Lower body's segmental acceleration (m/s^2) in 40m Fast-paced walk test, Stair climb test, and 2-minute walk at the subject's preferred pace will be assessed by Inertial Measurement Unit (IMU).	Baseline, 8 months, 20 months