Finding the Optimal Resistance Training Intensity For Your Bones

Sponsor

University of Waterloo (Other)

Overall Status

Recruiting

CT.gov ID

NCT05541432

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), University of Saskatchewan (Other), University Health Network, Toronto (Other)

324

Enrollment

Location

Arms

Anticipated Duration (Months)

6.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Osteoporosis is a bone disease that can result in fractures, disability and an increased risk of premature death. Exercise is recommended for fall and fracture prevention, but health care professionals often recommend walking or lower intensity community exercise classes, which may not be effective for building bone. Further, individuals with osteoporosis are often told to avoid lifting or moving in certain ways, which creates fear and activity avoidance. Conversely, research suggests that to stimulate bone, you need higher loads on bone, with either higher intensity resistance training or impact exercise - the types of things people with low bone mass are told to avoid. Our study will examine different types of exercise intensity and how they translate to building bone in people with low bone mineral density (BMD).

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis Osteopenia	Other: Supervised strength training (group 1) Other: Supervised strength training (group 2) Other: Home exercise	N/A

Detailed Description

The FORTIFY Bones study will compare the effect of supervised twice-weekly progressive resistance training (PRT) for one year to a home posture and balance exercise program on lumbar spine bone mineral density (BMD).Secondary outcomes include fractures, falls, body composition, quality of life, and health service use. As secondary analyses, we will examine the differences between each resistance training intensity and control, and between resistance training intensities on all outcomes. For the study, we are recruiting men and post-menopausal women age 50 or over who are at risk of fragility fractures. Participants will be randomized to one of three exercise programs to be completed twice weekly: posture and balance exercise program at home, in-person, supervised progressive resistance training at 70% of estimated 1 Repetition Maximum (1RM) intensity, or in-person, supervised progressive resistance training at an 85% estimated 1RM intensity. The study is a multi-centre trial that will take place at the University of Waterloo, Toronto General Hospital, and the University of Saskatchewan. The long-term goal of this study is to generate evidence to support decision-making on the type of exercises for people with osteoporosis.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

324 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomized in a 1:1:1 ratio to one of three arms. Participants will perform exercise or control activities twice weekly for 12 months. Not all participants will start and end at the same time.Participants will be randomized in a 1:1:1 ratio to one of three arms. Participants will perform exercise or control activities twice weekly for 12 months. Not all participants will start and end at the same time.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Investigators and outcome assessors will be masked to the group allocation of participants. Participants will be masked to the hypothesis of the study.

Primary Purpose:

Treatment

Official Title:

Finding the Optimal Resistance Training Intensity For Your Bones: A Randomized Controlled Trial (FORTIFY Bones)

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Home exercise Home exercise program, with biweekly group virtual education and exercise classes.	Other: Home exercise Participants in this arm will complete twice-weekly upper and lower body exercises at home, focused on posture and balance. Participants will meet 1:1 with an exercise physiologist who will select and prescribe exercises. Participants will also be invited to attend twice monthly virtual exercise and education sessions.
Experimental: Supervised strength training (group 1) In-person, supervised muscle strengthening exercises twice weekly at a specific intensity.	Other: Supervised strength training (group 1) Participants in this arm will complete twice weekly resistance training. They will focus on form initially, and then be progressed to 3 sets of 10-12 repetitions at an intensity of ~70% of estimated 1 repetition maximum.
Experimental: Supervised strength training (group 2) In-person, supervised muscle strengthening exercises twice weekly at a specific intensity.	Other: Supervised strength training (group 2) Participants in this arm will complete twice weekly resistance training. They will focus on form initially, and then be progressed to 3 sets of ~4-6 repetitions at an intensity of 85% of estimated one repetition maximum, with a warm-up set of 8 repetitions at their estimated 70% estimated one repetition maximum to attempt to match the volume performed in the other resistance training group.

Arm

Intervention/Treatment

Active Comparator: Home exercise

Home exercise program, with biweekly group virtual education and exercise classes.

Other: Home exercise

Participants in this arm will complete twice-weekly upper and lower body exercises at home, focused on posture and balance. Participants will meet 1:1 with an exercise physiologist who will select and prescribe exercises. Participants will also be invited to attend twice monthly virtual exercise and education sessions.

Experimental: Supervised strength training (group 1)

In-person, supervised muscle strengthening exercises twice weekly at a specific intensity.

Other: Supervised strength training (group 1)

Participants in this arm will complete twice weekly resistance training. They will focus on form initially, and then be progressed to 3 sets of 10-12 repetitions at an intensity of ~70% of estimated 1 repetition maximum.

Experimental: Supervised strength training (group 2)

In-person, supervised muscle strengthening exercises twice weekly at a specific intensity.

Other: Supervised strength training (group 2)

Participants in this arm will complete twice weekly resistance training. They will focus on form initially, and then be progressed to 3 sets of ~4-6 repetitions at an intensity of 85% of estimated one repetition maximum, with a warm-up set of 8 repetitions at their estimated 70% estimated one repetition maximum to attempt to match the volume performed in the other resistance training group.

Outcome Measures

Primary Outcome Measures

Lumbar Spine BMD [Baseline and 12 months]
Lumbar spine (L1-L4) bone mineral density measured via DXA scan.

Secondary Outcome Measures

Fractures [Over 12 months]
Composite outcome of new non-vertebral and vertebral fractures, and progression of existing vertebral fractures. We will report the number in each category separately. We will use a fracture questionnaire for non-vertebral fractures, and vertebral fractures that come to clinical attention. Participants will undergo a DXA scan for Vertebral Fracture Assessment (VFA) at baseline and the 12-months. A vertebral fracture will be defined as having a radiographic presence of ≥25% reduction in anterior, middle, or posterior vertebral height, verified by an experienced radiologist at University Health Network via the Genant visual semi-quantitative method. Baseline VFA will be assessed for vertebral fractures and compared to VFA at 12 months to ascertain if there has been progression of new fractures; progression will be defined as progression to a new Genant level or a change in height of at least 10%.
Rate of falls per person per year [Over 12 months]
Participants will be emailed a falls calendar via a REDCap survey at the end of each month. Participants will be asked to immediately report any falls to research assistant and to exercise physiologist. Exercise physiologists will report any noted falls to their study coordinator immediately and additional follow-up documentation will be required. Rate of falls and number of people who experience one or more falls will be compared between groups.
Number of people who experience one or more falls [Over 12 months]
Participants will be emailed a falls calendar via a REDCap survey at the end of each month. Participants will be asked to immediately report any falls to research assistant and to exercise physiologist. Exercise physiologists will report any noted falls to their study coordinator immediately and additional follow-up documentation will be required. Rate of falls and number of people who experience one or more falls will be compared between groups.
Bone-free lean mass [Baseline and 12 months]
Whole body fat- and bone-free lean mass (FBFM, kg) will be derived from DXA scans.
Appendicular lean mass [Baseline and 12 months]
We will calculate appendicular lean mass (kg) and its index (kg/m^2) from appendicular bone-free lean mass and height (cm).
Height [Baseline and 12 months]
Height will be a proxy measure of posture.
Occiput-to-wall distance [Baseline and 12 months]
Occiput-to-wall distance will be a proxy measure of posture.
Knee extension peak torque [Baseline, 6 months, and 12 months]
We will assess isometric knee extension peak torque using a knee extension test with a dynamometer.
30 Second Chair Stand Test. [Baseline, 6 months, and 12 months]
We will use the 30 Second Chair Stand Test.
Four Square Step Test [Baseline, 6 months, and 12 months]
We will use the Four Square Step Test to assess lower extremity muscle power and dynamic balance during functional tasks.
Grip Strength [Baseline, 6 months, and 12 months]
We will assess grip strength of the non-dominant arm using a hand dynamometer.
10 Metre Walk Test. [Baseline, 6 months, and 12 months]
We will assess gait speed using the 10 Metre Walk Test.
6 Minute Walk Test. [Baseline, 6 months, and 12 months]
We will assess endurance using the 6 Minute Walk Test.
QUALEFFO-41 [Baseline, 6 months, and 12 months]
We will use the QUALEFFO-41 as an osteoporosis specific measure of health-related quality of life.
EQ5D5L [Baseline, 6 months, and 12 months]
We will use the EQ5D5L measure as a generic health-related quality of life measure.
Serious adverse events [Over 12 months]
We will ask participants to report adverse events, using Health Canada definitions. We will report all serious and non-serious adverse events and identify those attributable to intervention. Safety outcomes will include all falls, fractures, and serious and non-serious adverse events. Any fractures or falls that are attributable to intervention will be considered under both fall or fracture outcomes, and harms.
Non-serious adverse events [Over 12 months]
We will ask participants to report adverse events, using Health Canada definitions. We will report all serious and non-serious adverse events and identify those attributable to intervention. Safety outcomes will include all falls, fractures, and serious and non-serious adverse events. Any fractures or falls that are attributable to intervention will be considered under both fall or fracture outcomes, and harms.
Glucose concentration [Baseline and 6 months]
We will be taking a fasted blood sample from participants to measure plasma glucose concentrations using biochemical assay. Blood samples will only be collected from participants at the University of Waterloo site.
Insulin concentration [Baseline and 6 months]
We will be taking a fasted blood sample from participants to measure serum insulin concentrations using radioimmunoassay. Blood samples will only be collected from participants at the University of Waterloo site.
Pro/anti-inflammatory markers (including TNFalpha, IL-6, IL-10, IL-15) [Baseline and 6 months]
We will be taking a fasted blood sample from participants to measure plasma pro- and anti-inflammatory markers using a multiplex kit. Blood samples will only be collected from participants at the University of Waterloo site.
Oxidative stress markers/antioxidant status (including oxygen radical absorbance capacity (ORAC) assay, protein carbonyls, glutathione peroxidase activity, thyroredoxin, malondialdehyde) [Baseline and 6 months]
We will be taking a fasted blood sample from participants to measure antioxidant status and markers of oxidative stress using commercially available assays. Blood samples will only be collected from participants at the University of Waterloo site.
Myokines [Baseline and 6 months]
We will be taking fasting blood samples from participants to measure myokines via the Luminex Performance Assay. Blood samples will only be collected from participants at the University of Waterloo site.
Total Hip BMD [Baseline and 12 months]
Bone mineral density of the hip measured via DXA scans
Femoral Neck BMD [Baseline and 12 months]
Bone mineral density of the femoral neck measured via DXA scans
Trabecular Bone Score [Baseline and 12 months]
Trabecular bone score (TBS) will be calculated using TBS iNsight software. A high TBS value indicates high quality boner structure, whereas a low TBS value demonstrates a lower quality structure. The TBS index ranges from 0.9 - 1.6.
Hip Geometry [Baseline and 12 months]
We will use the DXA scanner's hip structural analysis feature to calculate estimates of hip geometry from proximal femur scans.
Health Service Use [Baseline, 6 months, and 12 months]
We will assess direct medical resources (e.g., tests, medications, hospitalization, rehabilitation), direct non-medical resources (e.g., out of pocket expenses, transportation), indirect resources (e.g., iMTA Productivity Cost Questionnaire) and clinical events and management. We will assess resource use for incident falls, fractures or adverse events. Multiplying resources collected by jurisdictional unit costs in Canadian dollars will determine the total cost per exercise program.
Ratio of costs to QALY [Baseline, 6 months, and 12 months]
We will calculate the ratio of incremental costs between the interventions, determined by trial resources, and clinical outcome (QALY) to achieve an incremental cost per life year gained outcome.
Willingness to pay [Baseline, 6 months, and 12 months]
We will assess willingness to pay for various exercise models using a contingent valuation survey.
Body weight [Baseline, 6 months and 12 months]
Body weight in kg measured using scale

Other Outcome Measures

Markers of bone metabolism [Baseline and 6 months]
We will store fasting blood samples with the intent of measuring ionized calcium, carboxy-terminal collagen crosslinks (CTX), parathyroid hormone (PTH), vitamin D, sclerostin, and amino-terminal propeptide of type 1 procollagen (P1NP) if we have sufficient budget to perform these analyses. Blood samples will be taken at the University of Waterloo site only.
Dietary Intake [Baseline, 6 months, and 12 months]
We will use ASA24 to collect information on the participant's dietary intake through the self-administered 24-hour dietary record. Participants will report all food and beverage items and quantities on 3 days (2 weekday, 1 weekend day) at baseline, 6 months, and 12 months. We will also use the SCREEN2 tool at baseline only. We will report descriptive data on energy, protein, calcium, and vitamin D intake. We will perform subgroup analyses: 1) Baseline daily calcium (<1000 vs. >1000 mg per day); and 2) Baseline protein intake (<1.2g/kg body weight per day). We will explore changes in participants who are referred to a dietitian for counselling because of low intakes of protein, calcium, or vitamin D.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 50 or over
Has received 2 vaccines for COVID-19
Has femoral neck, total hip, or lumbar spine BMD T-score of ≤ -1, OR has been or have a FRAX probability of fracture of greater than or equal to 20% for major osteoporotic fracture or 3% or greater for hip fracture.*
Individuals at high risk of fracture (i.e., risk in next 10 years is >20% according to FRAX) should be offered medication for osteoporosis. We will only include individuals at high risk of fracture who have declined medication or who had been on osteoporosis medication and decided to cease taking it in the appropriate timeline (as outlined by PI's and Physician).
Willing to participate in 2x weekly exercise sessions
Self-reported as postmenopausal for ≥ 2 years, OR postmenopausal stats confirmed via blood test (female participants only)

Exclusion Criteria:

Is unable to communicate in English
Has conditions affecting bone health
Takes or has taken medications affecting bone in the last 12 months or longer (as determined by the research team)
Has had a clinical or symptomatic spine fracture in the last 12 months, or a lower/upper limb fracture in the last 6 months
Has had a joint replacement in the last 6 months
Is receiving palliative care
Has major surgery planned in the next 12 months
Has had cancer within the last 2 years (excluding non-melanoma skin cancer)
Has planned travel time of greater than 6 weeks
Has been diagnosed with dementia
Is already participating in moderate- or high-intensity progressive resistance training ≥ twice weekly
Weighs over 450 lbs
Has contraindications to resistance training