Finding the Optimal Resistance Training Intensity For Your Bones

Osteoporosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05541432
• Other study ID #: 41337
• Status: Recruiting
• Phase: N/A
• Start date: September 13, 2022
• Est. completion date: September 2026

Study information

• Verified date: November 2022
• Source: University of Waterloo
• Contact: Kylie Sullivan, MSc
• Phone: 519-904-0660
• Email: krsullivan[@]uwaterloo.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 324
• Est. completion date: September 2026
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Diseases, Metabolic
• Osteopenia
• Osteoporosis

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Canada	University of Waterloo	Waterloo	Ontario

Sponsors (4)

Lead Sponsor	Collaborator
University of Waterloo	Canadian Institutes of Health Research (CIHR), University Health Network, Toronto, University of Saskatchewan

Country where clinical trial is conducted

Canada, 

References & Publications (14)

Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D. Risk of mortality following clinical fractures. Osteoporos Int. 2000;11(7):556-61. — View Citation

Costa AG, Wyman A, Siris ES, Watts NB, Silverman S, Saag KG, Roux C, Rossini M, Pfeilschifter J, Nieves JW, Netelenbos JC, March L, LaCroix AZ, Hooven FH, Greenspan SL, Gehlbach SH, Díez-Pérez A, Cooper C, Compston JE, Chapurlat RD, Boonen S, Anderson FA Jr, Adachi JD, Adami S. When, where and how osteoporosis-associated fractures occur: an analysis from the Global Longitudinal Study of Osteoporosis in Women (GLOW). PLoS One. 2013 Dec 11;8(12):e83306. doi: 10.1371/journal.pone.0083306. eCollection 2013. — View Citation

Duckham RL, Masud T, Taylor R, Kendrick D, Carpenter H, Iliffe S, Morris R, Gage H, Skelton DA, Dinan-Young S, Brooke-Wavell K. Randomised controlled trial of the effectiveness of community group and home-based falls prevention exercise programmes on bone health in older people: the ProAct65+ bone study. Age Ageing. 2015 Jul;44(4):573-9. doi: 10.1093/ageing/afv055. Epub 2015 Apr 23. — View Citation

El-Khoury F, Cassou B, Charles MA, Dargent-Molina P. The effect of fall prevention exercise programmes on fall induced injuries in community dwelling older adults: systematic review and meta-analysis of randomised controlled trials. BMJ. 2013 Oct 29;347:f6234. doi: 10.1136/bmj.f6234. Review. — View Citation

Gillespie LD, Robertson MC, Gillespie WJ, Sherrington C, Gates S, Clemson LM, Lamb SE. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2012 Sep 12;(9):CD007146. doi: 10.1002/14651858.CD007146.pub3. Review. — View Citation

Hopkins RB, Burke N, Von Keyserlingk C, Leslie WD, Morin SN, Adachi JD, Papaioannou A, Bessette L, Brown JP, Pericleous L, Tarride J. The current economic burden of illness of osteoporosis in Canada. Osteoporos Int. 2016 Oct;27(10):3023-32. doi: 10.1007/s00198-016-3631-6. Epub 2016 May 11. — View Citation

Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD000333. doi: 10.1002/14651858.CD000333.pub2. Review. — View Citation

Ioannidis G, Papaioannou A, Hopman WM, Akhtar-Danesh N, Anastassiades T, Pickard L, Kennedy CC, Prior JC, Olszynski WP, Davison KS, Goltzman D, Thabane L, Gafni A, Papadimitropoulos EA, Brown JP, Josse RG, Hanley DA, Adachi JD. Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study. CMAJ. 2009 Sep 1;181(5):265-71. doi: 10.1503/cmaj.081720. Epub 2009 Aug 4. — View Citation

Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, Licata A, Benhamou L, Geusens P, Flowers K, Stracke H, Seeman E. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001 Jan 17;285(3):320-3. — View Citation

Nikander R, Gagnon C, Dunstan DW, Magliano DJ, Ebeling PR, Lu ZX, Zimmet PZ, Shaw JE, Daly RM. Frequent walking, but not total physical activity, is associated with increased fracture incidence: a 5-year follow-up of an Australian population-based prospective study (AusDiab). J Bone Miner Res. 2011 Jul;26(7):1638-47. doi: 10.1002/jbmr.363. — View Citation

Rikkonen T, Salovaara K, Sirola J, Kärkkäinen M, Tuppurainen M, Jurvelin J, Honkanen R, Alhava E, Kröger H. Physical activity slows femoral bone loss but promotes wrist fractures in postmenopausal women: a 15-year follow-up of the OSTPRE study. J Bone Miner Res. 2010 Nov;25(11):2332-40. doi: 10.1002/jbmr.143. — View Citation

Sherrington C, Fairhall NJ, Wallbank GK, Tiedemann A, Michaleff ZA, Howard K, Clemson L, Hopewell S, Lamb SE. Exercise for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2019 Jan 31;1:CD012424. doi: 10.1002/14651858.CD012424.pub2. — View Citation

Sherrington C, Tiedemann A, Fairhall N, Close JC, Lord SR. Exercise to prevent falls in older adults: an updated meta-analysis and best practice recommendations. N S W Public Health Bull. 2011 Jun;22(3-4):78-83. doi: 10.1071/NB10056. Review. — View Citation

Tricco AC, Thomas SM, Veroniki AA, Hamid JS, Cogo E, Strifler L, Khan PA, Robson R, Sibley KM, MacDonald H, Riva JJ, Thavorn K, Wilson C, Holroyd-Leduc J, Kerr GD, Feldman F, Majumdar SR, Jaglal SB, Hui W, Straus SE. Comparisons of Interventions for Preventing Falls in Older Adults: A Systematic Review and Meta-analysis. JAMA. 2017 Nov 7;318(17):1687-1699. doi: 10.1001/jama.2017.15006. Review. Erratum in: JAMA. 2021 Apr 27;325(16):1682. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Dietary Intake	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, and perform exploratory analyses of changes in these outcomes over time. 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.	Baseline, 6 months, and 12 months
Primary	Lumbar Spine BMD	Lumbar spine (L1-L4) bone mineral density measured via DXA scan.	Baseline and 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Bone-free lean mass	Whole body fat- and bone-free lean mass (FBFM, kg) will be derived from DXA scans.	Baseline and 12 months
Secondary	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
Secondary	Height	Height will be a proxy measure of posture.	Baseline and 12 months
Secondary	Occiput-to-wall distance	Occiput-to-wall distance will be a proxy measure of posture.	Baseline and 12 months
Secondary	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
Secondary	30 Second Chair Stand Test.	We will use the 30 Second Chair Stand Test.	Baseline, 6 months, and 12 months
Secondary	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
Secondary	Grip Strength	We will assess grip strength of the non-dominant arm using a hand dynamometer.	Baseline, 6 months, and 12 months
Secondary	10 Metre Walk Test.	We will assess gait speed using the 10 Metre Walk Test.	Baseline, 6 months, and 12 months
Secondary	6 Minute Walk Test.	We will assess endurance using the 6 Minute Walk Test.	Baseline, 6 months, and 12 months
Secondary	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
Secondary	EQ5D5L	We will use the EQ5D5L measure as a generic health-related quality of life measure.	Baseline, 6 months, and 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Total Hip BMD	Bone mineral density of the hip measured via DXA scans	Baseline and 12 months
Secondary	Femoral Neck BMD	Bone mineral density of the femoral neck measured via DXA scans	Baseline and 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Willingness to pay	We will assess willingness to pay for various exercise models using a contingent valuation survey.	Baseline, 6 months, and 12 months
Secondary	Body weight	Body weight in kg measured using scale	Baseline, 6 months and 12 months