Effects of Multicomponent Exercise on Subchondral Bone and Cartilage in Postmenopausal Women With Knee Osteoarthritis (LuRu2)

Effects of a Multicomponent Exercise Regimen on Subchondral Bone, Cartilage, and Inflammation Markers in Postmenopausal Women With Knee Osteoarthritis: A Randomized Controlled Study

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Behavioral: Multicomponent exercise regimen; Behavioral: Standard rehabilitative management

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.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Jyväskylä, Finland, 40014
    • University of Jyväskylä

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: multicomponent exercise group; 8 months of multicomponent exercise (3 sessions/week).	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.
Active Comparator: Reference group; 8 months of standard rehabilitative care based home exercises.	Behavioral: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Tibiofemoral articular cartilage thickness (mm)	Assessed by 3D-texture analysis.	Baseline, 8 months, 20 months
Tibiofemoral articular cartilage volume (mm^3)	Assessed by 3D-texture analysis.	Baseline, 8 months, 20 months
Tibiofemoral subchondral bone mineral density (g/cm^3)	Assessed by high-resolution cone beam computed tomography (CBCT).	Baseline, 8 months, 20 months
Tibiofemoral subchondral bone mineral content (g)	Assessed by high-resolution CBCT.	Baseline, 8 months, 20 months
Tibiofemoral joint space narrowing (mm)	Assessed by high-resolution CBCT.	Baseline, 8 months, 20 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral content (BMC, g) of the femoral neck	Assessed by Dual-energy X-ray absorptiometry (DXA).	Baseline, 8 months, 20 months
Areal bone mineral density (aBMD, g/cm^2) of the femoral neck	Assessed by DXA.	Baseline, 8 months, 20 months
Cortical thickness (mm) of the femoral neck	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Femoral neck width (mm)	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Cross-sectional area (cm^2) of the femoral neck	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Cross-sectional moment of inertia (cm^4) of the femoral neck	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Section modulus (cm^3) of the femoral neck	Assessed by Advanced Hip Analysis software.	Baseline, 8 months, 20 months
Total body fat percentage (%)	Assessed by DXA.	Baseline, 8 months, 20 months
Fat Free Mass Index (FFMI, kg/m^2)	Assessed by DXA.	Baseline, 8 months, 20 months
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
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
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
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
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
Quantity of painkillers consumed	Assessed by diary.	Through the 8-month study intervention
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
Metabolic profile	Circulating metabolomes including resistin, leptin, adiponectin, lipids, lipoproteins, and metabolites will be assessed from blood.	Baseline, 8 months, 20 months
Cardiorespiratory fitness	Assessed by UKK 2km walk test (minutes and seconds).	Baseline, 8 months, 20 months
Knee extension and flexion maximal isometric muscle strength	Assessed by an adjustable dynamometer chair (Newtons).	Baseline, 8 months, 20 months
Static balance	Assessed by a single leg stance test (seconds).	Baseline, 8 months, 20 months
30 second chair-stand test (seconds)		Baseline, 8 months, 20 months
Timed up and go (TUG) (seconds)		Baseline, 8 months, 20 months
40m Fast-paced walk test (seconds)		Baseline, 8 months, 20 months
Stair climb test (seconds)		Baseline, 8 months, 20 months
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

Collaborators and Investigators

• Sponsor: University of Jyvaskyla
• Collaborators: University of Oulu; UKK Institute; Wellbeing Services County of Central Finland; Research Council of Finland
• Investigators: Principal Investigator: Ari Heinonen, Prof., emeritus, University of Jyväskylä

Publications and helpful links

General Publications

• 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.
• Konola VM, Parkkari J, Multanen J, Nikander R, Rantalainen T, Vesanto J, Pekkala S, Kalaja M, Ihalainen JK, Waller B, Munukka M, Sievanen H, Nevalainen M, Kautiainen H, Casula V, Paloneva J, Vasankari T, Peuna A, Saarakkala S, Nieminen MT, Heinonen A. Effects of a multicomponent exercise regimen on subchondral bone and cartilage in postmenopausal women with knee osteoarthritis: protocol for a randomized controlled trial. Trials. 2025 Jun 23;26(1):222. doi: 10.1186/s13063-025-08928-1.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Actual): December 10, 2025
• Study Completion (Actual): December 11, 2025

Study Registration Dates

• First Submitted: October 31, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; Osteoarthritis; Randomized controlled trial; Physiotherapy; Joint Diseases; Musculoskeletal Diseases; Cartilage; Postmenopausal women; Physical functioning; Subchondral bone
• Additional Relevant MeSH Terms: Arthritis; Rheumatic Diseases; Behavior; Joint Diseases; Osteoarthritis; Osteoarthritis, Knee; Musculoskeletal Diseases; Motor Activity
• Other Study ID Numbers: 21000057531; 351483 (Other Grant/Funding Number: Academy of Finland)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD cannot be anonymized and will thus remain restricted due to personal data protection. The basic project-level discovery metadata of the dataset(s) will be made openly available in the University's repository with a DOI for permanent findability and accessibility whenever the metadata are sufficiently complete to be published.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No