Clinical trial NCT05889598: Resistance Exercise Training to Improve Bone and Articular Cartilage Health in Women
Official title: Effects of a Resistance Exercise Programme on Risk of Osteoporosis and Osteoarthritis in Females
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Osteoporosis
Osteoarthritis
Keywords: Exercise
Explosive high-velocity
Bone mineral density
Knee joint
Neuromuscular
Biomarkers
Lead sponsor: Loughborough University
Sponsor class: OTHER
Collaborators: name: Versus Arthritis
First posted: 2023-06-05
Enrollment: 110
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Femoral neck bone mineral content from baseline
timeFrame: 32nd week
measure: Change in Femoral neck bone mineral density from baseline
timeFrame: 32nd week
Secondary outcomes:
measure: Bone Mineral Content (Femur)
timeFrame: Baseline, 16th and 32nd weeks
measure: Bone Mineral Density (Femur)
timeFrame: Baseline, 16th and 32nd weeks
measure: Bone Mineral Content (Spine)
timeFrame: Baseline, 16th and 32nd weeks
measure: Bone Mineral Density (Spine)
timeFrame: Baseline, 16th and 32nd weeks
measure: bone mineral content (Forearm)
timeFrame: Baseline, 16th and 32nd weeks
measure: bone mineral density (Forearm)
timeFrame: Baseline, 16th and 32nd weeks
measure: Bone mineral content (Lower leg)
timeFrame: Baseline, 16th and 32nd weeks
measure: bone mineral density (Lower Leg)
timeFrame: Baseline, 16th and 32nd weeks
measure: Bone mineral content (Total body)
timeFrame: Baseline, 16th and 32nd weeks
measure: bone mineral density (Total Body)
timeFrame: Baseline, 16th and 32nd weeks
measure: cortical bone subdensity (Forearm)
timeFrame: Baseline, 16th and 32nd weeks
measure: total bone density (Forearm)
timeFrame: Baseline, 16th and 32nd weeks
measure: trabecular bone density (Forearm)
timeFrame: Baseline, 16th and 32nd weeks
measure: bone total density (Forearm)
timeFrame: Baseline, 16th and 32nd weeks
measure: cortical bone density (Forearm)
timeFrame: Baseline, 16th and 32nd weeks
measure: total bone density (Lower leg)
timeFrame: Baseline, 16th and 32nd weeks
measure: trabecular bone density (Lower leg)
timeFrame: Baseline, 16th and 32nd weeks
measure: cortical bone subdensity (Lower leg)
timeFrame: Baseline, 16th and 32nd weeks
measure: bone total density (Lower leg)
timeFrame: Baseline, 16th and 32nd weeks
measure: cortical bone density (Lower leg)
timeFrame: Baseline, 16th and 32nd weeks
measure: total bone density (66% of Lower leg)
timeFrame: Baseline, 16th and 32nd weeks
measure: cortical density (Lower leg)
timeFrame: Baseline, 16th and 32nd weeks
measure: T2 relaxation time
timeFrame: Baseline and 32nd week
measure: cartilage thickness
timeFrame: Baseline and 32nd week
measure: Change in bone turnover biomarkers (CTX-1 and P1NP) in bodily samples
timeFrame: Baseline, 16th and 32nd weeks
measure: Lower limb power
timeFrame: Baseline, 16th and 32nd weeks
measure: Lower limb force
timeFrame: Baseline, 16th and 32nd weeks
measure: Lower limb velocity
timeFrame: Baseline, 16th and 32nd weeks
measure: Quadriceps cross-sectional area
timeFrame: Baseline and 32nd week
measure: Triceps surae cross-sectional area
timeFrame: Baseline and 32nd week
measure: Lower extremity functioning
timeFrame: Baseline, 16th and 32nd weeks
measure: Mobility/agility
timeFrame: Baseline, 16th and 32nd weeks
measure: Pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life following knee injury
timeFrame: Baseline, 16th and 32nd weeks
measure: Pain, stiffness, and physical function of the hip and knee
timeFrame: Baseline, 16th and 32nd weeks
measure: Physical Activity Level
timeFrame: Baseline, 16th and 32nd weeks
measure: Physical activity and inactivity level
timeFrame: Baseline, 16th and 32nd weeks
measure: Daily calcium intake
timeFrame: Baseline, 16th and 32nd weeks
measure: Static postural sway
timeFrame: Baseline, 16th and 32nd weeks
measure: Static postural sway (elliptical area)
timeFrame: Baseline, 16th and 32nd weeks
Other outcomes:
Locations:
city: Loughborough
country: United Kingdom
facility: Loughborough University
state: Leicestershire
Study officials:
affiliation: Loughborough University
name: Katherine Brooke-Wavell, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Loughborough University
name: Jonathan Folland, PhD
role: PRINCIPAL_INVESTIGATOR
References: