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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
324
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.
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.
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.
University of Waterloo
Waterloo, Ontario, Canada
University of Toronto
Markham, Canada
University of Saskatchewan
Saskatoon, Canada
Lumbar Spine bone mineral density (BMD)
Lumbar spine (L1-L4) bone mineral density measured via dual-energy X-ray Absorptiometry (DXA) scan.
Time frame: Baseline and 12 months
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%.
Time frame: Over 12 months
Rate of falls per person per year
Participants will be emailed a falls calendar via a 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.
Time frame: Over 12 months
Number of people who experience one or more falls
Participants will be emailed a falls calendar via a 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.
Time frame: Over 12 months
Bone-free lean mass
Whole body fat- and bone-free lean mass will be derived from DXA scans.
Time frame: 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).
Time frame: Baseline and 12 months
Height
Height will be a proxy measure of posture.
Time frame: Baseline and 12 months
Occiput-to-wall distance
Occiput-to-wall distance will be a proxy measure of posture.
Time frame: Baseline and 12 months
Knee extension peak torque
We will assess isometric knee extension peak torque using a knee extension test with a dynamometer.
Time frame: Baseline, 6 months, and 12 months
30 Second Chair Stand Test.
We will use the 30 Second Chair Stand Test.
Time frame: 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.
Time frame: Baseline, 6 months, and 12 months
Grip Strength
We will assess grip strength of the non-dominant arm using a hand dynamometer.
Time frame: Baseline, 6 months, and 12 months
10 Metre Walk Test.
We will assess gait speed using the 10 Metre Walk Test.
Time frame: Baseline, 6 months, and 12 months
6 Minute Walk Test.
We will assess endurance using the 6 Minute Walk Test.
Time frame: Baseline, 6 months, and 12 months
Osteoporosis-specific quality of life (QUALEFFO-41)
We will use the QUALEFFO-41 as an osteoporosis specific measure of health-related quality of life.
Time frame: Baseline, 6 months, and 12 months
Quality of life (EQ5D5L)
We will use the EQ5D5L measure as a generic health-related quality of life measure.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline and 6 months
Pro/anti-inflammatory markers
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.
Time frame: Baseline and 6 months
Oxidative stress markers/antioxidant status (including oxygen radical absorbance capacity (ORAC) assay, protein carbonyls, glutathione peroxidase activity, thioredoxin, 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.
Time frame: Baseline and 6 months
peptides synthesized and released by myocytes in muscle tissue
We will be taking fasting blood samples from participants to measure peptides synthesized and released by myocytes in muscle tissue via the Luminex Performance Assay. Blood samples will only be collected from participants at the University of Waterloo site.
Time frame: Baseline and 6 months
Total Hip BMD
Bone mineral density of the hip measured via DXA scans
Time frame: Baseline and 12 months
Femoral Neck BMD
Bone mineral density of the femoral neck measured via DXA scans
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, 6 months, and 12 months
Willingness to pay
We will assess willingness to pay for various exercise models using a contingent valuation survey.
Time frame: Baseline, 6 months, and 12 months
Body weight
Body weight in kg measured using scale
Time frame: Baseline, 6 months and 12 months
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