Resistance Exercise Training to Improve Bone and Articular Cartilage Health in Women

Osteoarthritis Clinical Trial

— REPROOF  

Official title:

Effects of a Resistance Exercise Programme on Risk of Osteoporosis and Osteoarthritis in Females

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05889598
• Other study ID #: 304156
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 1, 2022
• Est. completion date: December 2025

Study information

• Verified date: June 2023
• Source: Loughborough University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Osteoarthritis (degenerative joint disease) and osteoporosis (weak and fragile bones) are common conditions, particularly in women after menopause, and become even more common as we get older. Aging is also associated with sarcopenia, the progressive loss of muscle strength and mass with age. In this three-arm study, the effect of resistance exercise programs with different parameters (such as velocity and load) on various outcomes, including structural changes (bone mineral density, cartilage composition, muscle size), physical function, and biomarkers will be compared.

Description:

Resistance exercise is effective in improving several risk factors for osteoporosis and osteoarthritis, and is recommended to prevent and manage both conditions, and is also known to counteract sarcopenia. Overall, there is little and inconsistent evidence on the effects of exercise parameters (such as velocity) for the prevention of osteoporosis and osteoarthritis, neither is there a comparison of different velocities on structural parameters and biomarkers. Although osteoporosis and osteoarthritis take a long time to develop, it is possible to look at changes in risk using scans of bones and joints -Dual-Energy X-ray absorptiometry (DXA), peripheral Quantitative Computed Tomography (pQCT), and Magnetic Resonance Imaging (MRI)-, blood and/or urine samples and symptoms.

This study aims to examine the effect of two different resistance exercise interventions (explosive high-velocity vs high-load low-velocity training) on structural changes on bone, articular knee and/or hip cartilage and muscle, as well as biomarkers.

The study will be a 32-week long randomized controlled trial including two exercise groups and one non-exercising control group.

Screening and baseline measurements will then be taken when anonymization is completed. Once participants have completed baseline testing, participants will be randomly assigned to one of the exercise groups or control groups using a block randomization technique. Participants will choose an envelope, prepared in batches of 11, which will contain a note saying either 'ballistic' or 'conventional or 'control' with a ratio of 4:4:3. This is to allow for greater drop-out in the exercise groups. It is not possible to blind the participant or researchers supervising the intervention to the group allocation.

The required exercise program involves two supervised sessions per week at Loughborough University, each lasting no longer than 60 minutes per session. Each session will involve 30-40 minutes of exercise and time to check any symptoms or queries with participants.

The exercises are designed to strengthen major muscle groups of the trunk and lower body, as well as to load bones that are affected by osteoporosis and the knee and hip joints that are commonly affected by osteoarthritis. Each exercise training session will take 30-40 minutes and include some whole-body warm-up and trunk exercises before completing the two main exercises: a hack squat and calf raise. These two main exercises will be done using resistance (weight training) machines in a dedicated exercise facility. Investigators chose a hack squat machine as it exercises many muscle groups and skeletal sites in one exercise, including the spine and lower limb rather than a small area. Additionally, it supports the spine, making it safe and comfortable to use.

The intervention will be personalized to the individual's ability, and loads will steadily increase as the participant improves. The load will be decided according to maximal muscular strength determined by calculation of 1-repetition maximum which will be renewed every month to monitor the progress of their muscle strength and use of the correct weight for training (in proportion to the strength). Participants will start off using light weights and these will increase as participants become stronger.

The two exercise groups will follow the same exercise programmes but using different speeds and weights: The conventional training group will perform the exercises slowly (conventionally), whilst the ballistic group will use lower loads and higher velocity as if trying to jump. Participants will be carefully guided and coached to perform all the exercises correctly and all the exercise training sessions will be supervised by qualified researchers to ensure safety throughout the study.

The control group will be asked to maintain their usual exercise and diet. Follow-up measurements will take place 16 and 32 weeks after the commencement of the exercise programme.

The sample size calculation is based on detecting differences in bone mineral density between each exercise group and the control group. Using an effect size of 0.75 (considered clinically meaningful), alpha of 0.05, and beta errors of 0.95, approximately 28 participants are needed for each group. However, the final sample size should cover a possible number of withdrawals. To allow for a 30% drop-out rate in exercise groups, 110 participants will be recruited for the study.

All data will be reported in the final work; any missing data will be accounted for with reasons for it missing. All measures described in the methodology will be reported, whether results are statistically significant or not. Data from all eligible participants will be included in an intention-to-treat analysis. Multiple imputation will be used for addressing the presence of missing data. The analysis will be repeated in good adherers i.e. those who attended at least 90% of the exercise sessions.

Descriptive statistics will be calculated to give information on mean values and variation (standard deviation) of the cohort. Normal distribution will be analysed using Shapiro-Wilk test. If variance is shown to be homogenous and distribution normal within the population then repeated measures analysis of variance (RM-ANOVA) will detect any significant differences between group (exercise versus control), time (baseline versus post-intervention) or group x time interaction.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: December 2025
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 50 Years to 70 Years

Eligibility

Inclusion Criteria:

• Women between 50-70 years;

• Experienced last menstrual cycle, hormonal contraception or menopausal hormone replacement therapy at least five years ago;

• Independent living and able to come into the university;

• Healthy women: not previously diagnosed with osteoporosis or knee osteoarthritis, other major medical conditions;

• Able to understand English.

Exclusion Criteria:

• Any existing symptomatic knee, hip, back injury or any medical conditions or injuries which would affect the ability or safety to perform exercise or influence bone/cartilage, including unstable angina, uncontrolled hypertension, a history of heart failure, and a history of cardiovascular disease and conditions;

• Taking medication affecting bone/cartilage metabolism;

• Regular (>once per week on average) participation in resistance training with loading greater than bodyweight or in high impact (impact greater than jogging);

• Blood pressure exceeding 150/90 mmHg;

• BMI > 30 kg/m2;

• Contraindications to MRI or DXA (e.g. Metallic implants);

• Osteoporotic (FRAX score according to which the participant would be advised to seek treatment);

• Fracture within the past year.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoporosis

Intervention

Other:
• Ballistic Resistance Lower Body Strength Training
The exercise programme involves two supervised sessions per week at University. Each session will involve 30-40 minutes of exercise, comprising warm-up , two main exercises: a hack squat and calf raise using a hack squat machine, and core exercises. After a warm-up period involving 5 minutes cycling and one set of 5 conventional repetitions at 40%1RM, the ballistic training group will complete eccentric phase hack squat exercise in approximately 3 seconds and the concentric phase as fast as possible with throwing type contractions. If participants can, participants will be allowed to take off in the concentric phase. To maintain high velocity in this group, lower loads will be used compared to the conventional group. The load will be decided according to regular maximal muscular strength test (1RM) to use of the correct weight for training (in proportion to the strength). Participants will start off using light weights and these will increase as participants become stronger.
• Conventional Resistance Lower Body Strength Training
The exercise programme involves two supervised sessions per week at Loughborough University. Each session will involve 30-40 minutes of exercise, comprising warm-up , two main exercises: a hack squat and calf raise using a hack squat machine, and core exercises. After a warm-up period involving 5 minutes cycling and one set of 5 conventional repetitions at 40% of 1RM, the conventional training group will complete eccentric and concentric phases of hack squatting exercises for approximately 3 seconds each, with appropriate breathing techniques. The load will be decided according to regular maximal muscular strength test (1RM) to use of the correct weight for training (in proportion to the strength). Participants will start off using light weights and these will increase as participants become stronger.

Locations

Country	Name	City	State
United Kingdom	Loughborough University	Loughborough	Leicestershire

Sponsors (2)

Lead Sponsor	Collaborator
Loughborough University	Versus Arthritis

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Femoral neck bone mineral content from baseline	(g) measured by DXA	32nd week
Primary	Change in Femoral neck bone mineral density from baseline	(g/cm^2) measured by DXA	32nd week
Secondary	Bone Mineral Content (Femur)	Proximal Femur bone will be assessed in "g" by DXA	Baseline, 16th and 32nd weeks
Secondary	Bone Mineral Density (Femur)	Proximal femur bone will be assessed (g/cm^2) by DXA	Baseline, 16th and 32nd weeks
Secondary	Bone Mineral Content (Spine)	Lumbar spine bone will be assessed (g) by DXA	Baseline, 16th and 32nd weeks
Secondary	Bone Mineral Density (Spine)	Lumbar spine will be assessed (g/cm^2) by DXA	Baseline, 16th and 32nd weeks
Secondary	bone mineral content (Forearm)	Forearm bone will be assessed (g) by DXA	Baseline, 16th and 32nd weeks
Secondary	bone mineral density (Forearm)	Forearm bone will be assessed (g/cm^2) by DXA	Baseline, 16th and 32nd weeks
Secondary	Bone mineral content (Lower leg)	Tibia bone will be assessed (g) by DXA	Baseline, 16th and 32nd weeks
Secondary	bone mineral density (Lower Leg)	Tibia bone will be assessed (g/cm^2) by DXA	Baseline, 16th and 32nd weeks
Secondary	Bone mineral content (Total body)	Whole body will be assessed (g) by DXA	Baseline, 16th and 32nd weeks
Secondary	bone mineral density (Total Body)	Whole body will be assessed (g/cm^2) by DXA	Baseline, 16th and 32nd weeks
Secondary	cortical bone subdensity (Forearm)	Radius bone 4% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	total bone density (Forearm)	Radius bone 4% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	trabecular bone density (Forearm)	Radius bone 4% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	bone total density (Forearm)	Radius bone 66% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	cortical bone density (Forearm)	Radius bone 66% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	total bone density (Lower leg)	Tibia bone 4% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	trabecular bone density (Lower leg)	Tibia bone 4% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	cortical bone subdensity (Lower leg)	Tibia bone 4% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	bone total density (Lower leg)	Tibia bone 38% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	cortical bone density (Lower leg)	Tibia bone 38% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	total bone density (66% of Lower leg)	Tibia bone 66% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	cortical density (Lower leg)	Tibia bone 66% (mg/cm^3) measured by pQCT	Baseline, 16th and 32nd weeks
Secondary	T2 relaxation time	Knee joint cartilage (ms) measured by MRI	Baseline and 32nd week
Secondary	cartilage thickness	Knee joint cartilage (mm) measured by MRI	Baseline and 32nd week
Secondary	Change in bone turnover biomarkers (CTX-1 and P1NP) in bodily samples	Serum/urine will be assessed by ELISA kits	Baseline, 16th and 32nd weeks
Secondary	Lower limb power	(W) measured during Hack squat action	Baseline, 16th and 32nd weeks
Secondary	Lower limb force	(N) measured during Hack squat action	Baseline, 16th and 32nd weeks
Secondary	Lower limb velocity	(m/s) measured during Hack squat action	Baseline, 16th and 32nd weeks
Secondary	Quadriceps cross-sectional area	(cm^2) measured by MRI	Baseline and 32nd week
Secondary	Triceps surae cross-sectional area	(cm^2) measured by pQCT	Baseline and 32nd week
Secondary	Lower extremity functioning	(total score in points) using Short Physical Performance Battery. SPPB scores range from zero to 12 possible points. SPPB score of 10 or greater for persons with no mobility disability indicates robustness.	Baseline, 16th and 32nd weeks
Secondary	Mobility/agility	The timed Up and Go test is rated on a scale from 1 to 5 where 1 indicates "normal function" and 5 indicates "severely abnormal function"	Baseline, 16th and 32nd weeks
Secondary	Pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life following knee injury	the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire will be used for that. A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems	Baseline, 16th and 32nd weeks
Secondary	Pain, stiffness, and physical function of the hip and knee	Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Usually a sum of the scores for all three subscales gives a total WOMAC score, however there are other methods that have been used to combine scores. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline, 16th and 32nd weeks
Secondary	Physical Activity Level	Bone-specific Physical Activity Questionnaire (BPAQ). higher scores mean higher physical and better outcomes for the study	Baseline, 16th and 32nd weeks
Secondary	Physical activity and inactivity level	International Physical Activity Questionnaire (IPAQ)	Baseline, 16th and 32nd weeks
Secondary	Daily calcium intake	(mg) Calcium Questionnaire	Baseline, 16th and 32nd weeks
Secondary	Static postural sway	anterior-posterior and medial-lateral mean velocity (cm/s) of the centre of pressure	Baseline, 16th and 32nd weeks
Secondary	Static postural sway (elliptical area)	the elliptical area (cm^2) will be assessed	Baseline, 16th and 32nd weeks