Finding the Optimal Resistance Training Intensity For Your Bones

Study Overview
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Brief Summary
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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).

Detailed Description
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The FORTIFY Bones study will compare the effect of supervised twice-weekly progressive resistance training (PRT) at moderate or high intensity for one year to a home posture and balance exercise program on lumbar spine bone mineral density (BMD), in individuals with low bone mass not taking osteoporosis medication. As secondary analyses, we will examine the differences between each resistance training intensity and home exercise, and between resistance training intensities on all outcomes. 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.

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

Conditions
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Osteoporosis, Osteopenia

Intervention / Treatment
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* Other: Supervised strength training (group 1)
* Other: Supervised strength training (group 2)
* Other: Home exercise


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Home exercise<br>Home exercise program, with biweekly group virtual education and exercise classes. | Other: Home exercise<br>* 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.<br>|
| Experimental: Supervised strength training (group 1)<br>In-person, supervised muscle strengthening exercises twice weekly at a specific intensity. | Other: Supervised strength training (group 1)<br>* 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.<br>|
| Experimental: Supervised strength training (group 2)<br>In-person, supervised muscle strengthening exercises twice weekly at a specific intensity. | Other: Supervised strength training (group 2)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lumbar Spine BMD | Lumbar spine (L1-L4) bone mineral density measured via DXA scan. | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractures | 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%. | Over 12 months | 
| Rate of falls per person per year | 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. | Over 12 months | 
| Number of people who experience one or more falls | 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. | Over 12 months | 
| Bone-free lean mass | Whole body fat- and bone-free lean mass (FBFM, kg) will be derived from DXA scans. | Baseline and 12 months | 
| Appendicular lean mass | We will calculate appendicular lean mass (kg) and its index (kg/m^2) from appendicular bone-free lean mass and height (cm). | Baseline and 12 months | 
| Height | Height will be a proxy measure of posture. | Baseline and 12 months | 
| Occiput-to-wall distance | Occiput-to-wall distance will be a proxy measure of posture. | Baseline and 12 months | 
| Knee extension peak torque | We will assess isometric knee extension peak torque using a knee extension test with a dynamometer. | Baseline, 6 months, and 12 months | 
| 30 Second Chair Stand Test. | We will use the 30 Second Chair Stand Test. | Baseline, 6 months, and 12 months | 
| Four Square Step Test | We will use the Four Square Step Test to assess lower extremity muscle power and dynamic balance during functional tasks. | Baseline, 6 months, and 12 months | 
| Grip Strength | We will assess grip strength of the non-dominant arm using a hand dynamometer. | Baseline, 6 months, and 12 months | 
| 10 Metre Walk Test. | We will assess gait speed using the 10 Metre Walk Test. | Baseline, 6 months, and 12 months | 
| 6 Minute Walk Test. | We will assess endurance using the 6 Minute Walk Test. | Baseline, 6 months, and 12 months | 
| QUALEFFO-41 | We will use the QUALEFFO-41 as an osteoporosis specific measure of health-related quality of life. | Baseline, 6 months, and 12 months | 
| EQ5D5L | We will use the EQ5D5L measure as a generic health-related quality of life measure. | Baseline, 6 months, and 12 months | 
| Serious adverse events | 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. | Over 12 months | 
| Non-serious adverse events | 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. | Over 12 months | 
| Glucose concentration | 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. | Baseline and 6 months | 
| Insulin concentration | 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. | Baseline and 6 months | 
| Pro/anti-inflammatory markers (including TNFalpha, IL-6, IL-10, IL-15) | 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. | Baseline and 6 months | 
| Oxidative stress markers/antioxidant status (including oxygen radical absorbance capacity (ORAC) assay, protein carbonyls, glutathione peroxidase activity, thyroredoxin, malondialdehyde) | 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. | Baseline and 6 months | 
| Myokines | 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. | Baseline and 6 months | 
| Total Hip BMD | Bone mineral density of the hip measured via DXA scans | Baseline and 12 months | 
| Femoral Neck BMD | Bone mineral density of the femoral neck measured via DXA scans | Baseline and 12 months | 
| Trabecular Bone Score | 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. | Baseline and 12 months | 
| Hip Geometry | We will use the DXA scanner's hip structural analysis feature to calculate estimates of hip geometry from proximal femur scans. | Baseline and 12 months | 
| Health Service Use | 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. | Baseline, 6 months, and 12 months | 
| Ratio of costs to QALY | 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. | Baseline, 6 months, and 12 months | 
| Willingness to pay | We will assess willingness to pay for various exercise models using a contingent valuation survey. | Baseline, 6 months, and 12 months | 
| Body weight | Body weight in kg measured using scale | Baseline, 6 months and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone fracture, Strength training, Exercise, Bone mineral density, Muscle strength, Resistance training