Bone Response to Exercise in Women on Antiresorptive Medications
NCT ID: NCT04275011
Last Updated: 2022-09-02
Study Results
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Basic Information
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TERMINATED
NA
26 participants
INTERVENTIONAL
2020-01-02
2020-03-16
Brief Summary
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Detailed Description
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The bone response to medications and exercise can be measured via the assessment of bone biomarkers present in the blood. For instance, sclerostin is a protein secreted by osteocytes and it can influence the bone remodeling process by inhibiting bone formation. Human genetic disorders deficient in sclerostin, such as sclerosteosis and Van Buchem's disease, have been associated with significant increases in bone mass. Therefore, decreasing sclerostin levels may be a potential treatment for people with low bone mass conditions. A case-control study demonstrated that postmenopausal women who adequately responded to bisphosphonates (e.g., did not experience a fracture while on treatment) had significantly lower serum sclerostin concentrations than those who experienced a fracture while taking bisphosphonates. There is also a link between sclerostin and exercise as a previous cross-sectional study reported an association between low serum sclerostin levels and increased physical activity duration. In addition, PRT and high impact exercise interventions have been shown to decrease sclerostin levels in healthy pre-menopausal women and thus may eventually increase bone mass or prevent bone loss. Therefore, changes in serum sclerostin levels can be used to provide insight regarding the bone response to antiresorptive medications as well as exercise.
Investigators plan to conduct a single-blinded parallel-group randomized controlled trial (RCT) with 1:1 allocation ratio to determine whether participants with low bone mass are able to adhere and safely perform PRT and impact exercises at an intensity that is hypothesized to stimulate bone. Specifically, the primary aim will be to determine the effects of moderate-high PRT and impact training on sclerostin in women on antiresorptive medication. The secondary aims are: a) to explore the effects of moderate-high PRT and impact training on BTMs \[serum N-terminal procollagen of type I collagen (P1NP), C-terminal cross-linked of type I collagen (CTX), parathyroid hormone (PTH), Vitamin D and serum calcium\], physical function and quality of life and body composition; b) to determine the feasibility of the intervention by assessing adherence, participant satisfaction with the intervention, and the acceptability of the attention control group; and c) to determine if there are any adverse events, including falls, fractures, or other adverse health outcomes attributable to the exercise intervention.
Investigators hypothesize that a moderate-to high PRT and impact exercise program will decrease sclerostin levels to a greater extent than the posture and balance exercise program. Further, it is hypothesized that PRT and impact exercise will result in more favourable improvements in other bone biomarkers, physical function, mobility, quality of life and body composition than the control group. Investigators hypothesize a low drop-out rate since both groups will be receiving the same level of attention throughout the study. Further, no adverse events attributable to exercise are expected. Kinesiologists who are Certified Exercise Physiologists will provide coaching on proper form, and will use appropriate progression of exercise intensity and volume.
Sample Size Estimation:
The sample size estimation was determined using data from a cross-sectional study that reported an association between low physical activity duration and high serum sclerostin levels. Women who engaged in less than 30 minutes of exercise per week had statistically significantly higher serum sclerostin levels than women who engaged in 60-120 minutes of physical activity per week (27.84 +/- 4.98 pmol/L vs. 21.64 +/- 6.21 pmol/L; p\<0.0001, respectively). The study described used a manual ELISA® kit to assess sclerostin which is consistent with the current study protocol. Based on the study findings, to detect a difference in serum sclerostin of 6.2 pmol/L with a standard deviation of 1.23 pmol/L investigators will need 38 participants using an alpha level of 0.05 and a power of 90%. Investigators assumed a 20% attrition rate for the current study therefore the estimated sample size was increased to 46 participants.
Analyses:
The study protocol was prepared according to the Standard Protocol Items: Recommendations for Interventional Trial (SPIRIT) guidelines. Reporting will be consistent with Consolidated Standards of Reporting Trials (CONSORT) non-pharmacological trials extension. The proposed study protocol is summarized. Participant characteristics and outcomes that are considered continuous variables will be reported as mean +/- standard deviation or median and interquartile range. Categorical data will be reported as number (%). Analyses of the feasibility and safety of the exercise intervention will be descriptive. A participant flow diagram will be used to demonstrate the number of participants who were randomly assigned to each group, who completed the exercise training program and who were analyzed for each outcome. For each group, losses or exclusions after randomization will be recorded along with reasons. Intention-to-treat analysis will be performed and thus all participants will be included in the analysis and analysed according to the group to which they were randomized. Differences in outcome measures will be assessed using analysis of covariance (ANCOVA) while adjusting for baseline demographic and clinical characteristics (e.g., age, smoking status, physical activity level, dietary intake). Investigators will also perform sensitivity analysis to determine if participants with ≥80% adherence criteria to the exercise intervention experience greater benefits. At the end of the study, investigators will assess whether allocation concealment was maintained among the blinded research staff and whether participants were aware of the study hypothesis. Statistical significance will be set at p \< or equal to 0.05. All data analysis will be conducted using the IBM Corporation Statistical Package for the Social Sciences (SPSS) version 24.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
OTHER
DOUBLE
Study Groups
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Static Posture and Balance Exercise
Participants in the control group will receive equal attention through a static posture and balance exercise class two times per week, in a small group setting.
Static Balance and Postural Exercise
Participants in the attention control group will perform static posture and balance exercises (e.g., low intensity yoga poses) and will be given the same attention as the participants in the intervention group. The small group exercises will be performed twice a week, 30-45 minutes per session, over 6 months, with at least one day of rest between each session. The exercise program will be supervised by a certified personal trainer and yoga instructor who is BoneFit trained.
Progressive Resistance and Impact Exercise
The exercise program will include two progressive resistance and impact exercise training sessions per week in a small group setting. Exercises will be individually tailored to the participants' abilities and designed to achieve a maximum 80-85% 1RM.
Progressive Resistance and Impact Exercise
Full body resistance and impact exercises will be performed twice a week for 30-45 minutes over a 6 month period. There will be at least one day of rest between scheduled exercise sessions. Participants will be individually prescribed variations of push, pull, squat, lift and carry movements targeting major muscle groups that they can safely complete, and accessory exercises to help develop movement patterns. Exercises will challenge both the upper and lower body using functional movement patterns. Each muscle group will be trained twice a week. During the first month, participants will focus on completing exercises with good form at a low intensity. Once form is mastered, exercises will be progressed (by increasing load, or challenge of the movement) to a moderate to high exercise intensity (80-85% 1RM) so that the participant can complete a maximum of 8 (\~80% 1RM) or 6 (\~85% 1RM) repetitions with 1-2 repetitions in reserve for 3 sets at a rating of perceived exertion (RPE) of 8-9.
Interventions
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Progressive Resistance and Impact Exercise
Full body resistance and impact exercises will be performed twice a week for 30-45 minutes over a 6 month period. There will be at least one day of rest between scheduled exercise sessions. Participants will be individually prescribed variations of push, pull, squat, lift and carry movements targeting major muscle groups that they can safely complete, and accessory exercises to help develop movement patterns. Exercises will challenge both the upper and lower body using functional movement patterns. Each muscle group will be trained twice a week. During the first month, participants will focus on completing exercises with good form at a low intensity. Once form is mastered, exercises will be progressed (by increasing load, or challenge of the movement) to a moderate to high exercise intensity (80-85% 1RM) so that the participant can complete a maximum of 8 (\~80% 1RM) or 6 (\~85% 1RM) repetitions with 1-2 repetitions in reserve for 3 sets at a rating of perceived exertion (RPE) of 8-9.
Static Balance and Postural Exercise
Participants in the attention control group will perform static posture and balance exercises (e.g., low intensity yoga poses) and will be given the same attention as the participants in the intervention group. The small group exercises will be performed twice a week, 30-45 minutes per session, over 6 months, with at least one day of rest between each session. The exercise program will be supervised by a certified personal trainer and yoga instructor who is BoneFit trained.
Eligibility Criteria
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Inclusion Criteria
* Taking anti-resorptive medications for at least 12 months eg. risedronate (Actonel), alendronate (Fosamax, Fosavance), etidronate (Didronel, Didrocal), zoledronic acid (Aclasta, Reclast, Zometa), pamidronate (Aredia) and denosumab (Prolia, Xgeva).
Exclusion Criteria
* Already participating in structured progressive resistance exercise or impact training exercise program; presence of any progressive neurological disorders that can possibly prevent study completion; unable to stand or walk 10 m with or without gait aid; does not have the mental capacity to provide informed consent; have any contraindications to exercise as determined by a physician.
* Individuals that have had a fracture in the last 6 months need to have completed any immobilization (eg. casting) and post-fracture rehabilitation, and will need physician consent to participate in the study. Individuals with previous fractures (\> 6 months ago) will not be excluded.
18 Years
FEMALE
Yes
Sponsors
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University of Waterloo
OTHER
Responsible Party
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Principal Investigators
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Lora M Giangregorio, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Waterloo, Schlegel-UW Research Institute for Aging
Locations
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University of Waterloo
Waterloo, Ontario, Canada
Countries
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References
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Swift JM, Nilsson MI, Hogan HA, Sumner LR, Bloomfield SA. Simulated resistance training during hindlimb unloading abolishes disuse bone loss and maintains muscle strength. J Bone Miner Res. 2010 Mar;25(3):564-74. doi: 10.1359/jbmr.090811.
Chilibeck PD, Davison KS, Whiting SJ, Suzuki Y, Janzen CL, Peloso P. The effect of strength training combined with bisphosphonate (etidronate) therapy on bone mineral, lean tissue, and fat mass in postmenopausal women. Can J Physiol Pharmacol. 2002 Oct;80(10):941-50. doi: 10.1139/y02-126.
Uusi-Rasi K, Kannus P, Cheng S, Sievanen H, Pasanen M, Heinonen A, Nenonen A, Halleen J, Fuerst T, Genant H, Vuori I. Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial. Bone. 2003 Jul;33(1):132-43. doi: 10.1016/s8756-3282(03)00082-6.
Martyn-St James M, Carroll S. A meta-analysis of impact exercise on postmenopausal bone loss: the case for mixed loading exercise programmes. Br J Sports Med. 2009 Dec;43(12):898-908. doi: 10.1136/bjsm.2008.052704. Epub 2008 Nov 3.
Basat H, Esmaeilzadeh S, Eskiyurt N. The effects of strengthening and high-impact exercises on bone metabolism and quality of life in postmenopausal women: a randomized controlled trial. J Back Musculoskelet Rehabil. 2013;26(4):427-35. doi: 10.3233/BMR-130402.
Erickson CR, Vukovich MD. Osteogenic index and changes in bone markers during a jump training program: a pilot study. Med Sci Sports Exerc. 2010 Aug;42(8):1485-92. doi: 10.1249/MSS.0b013e3181d0fa7a.
Watson S, Weeks B, Weis L, Harding A, Horan S, Beck B. High-Intensity Resistance and Impact Training Improves Bone Mineral Density and Physical Function in Postmenopausal Women With Osteopenia and Osteoporosis: The LIFTMOR Randomized Controlled Trial. J Bone Miner Res. 2019 Mar;34(3):572. doi: 10.1002/jbmr.3659. Epub 2019 Feb 25. No abstract available.
Watson SL, Weeks BK, Weis LJ, Horan SA, Beck BR. Heavy resistance training is safe and improves bone, function, and stature in postmenopausal women with low to very low bone mass: novel early findings from the LIFTMOR trial. Osteoporos Int. 2015 Dec;26(12):2889-94. doi: 10.1007/s00198-015-3263-2. Epub 2015 Aug 5.
Hamilton CJ, Swan VJ, Jamal SA. The effects of exercise and physical activity participation on bone mass and geometry in postmenopausal women: a systematic review of pQCT studies. Osteoporos Int. 2010 Jan;21(1):11-23. doi: 10.1007/s00198-009-0967-1. Epub 2009 Jun 6.
Beck BR, Daly RM, Singh MA, Taaffe DR. Exercise and Sports Science Australia (ESSA) position statement on exercise prescription for the prevention and management of osteoporosis. J Sci Med Sport. 2017 May;20(5):438-445. doi: 10.1016/j.jsams.2016.10.001. Epub 2016 Oct 31.
Kaastad TS, Nordsletten L, Narum S, Madsen JE, Haug E, Reikeras O. Training increases the in vivo fracture strength in osteoporotic bone. Protection by muscle contraction examined in rat tibiae. Acta Orthop Scand. 1996 Aug;67(4):371-6. doi: 10.3109/17453679609002334.
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.
Baron R, Rawadi G. Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology. 2007 Jun;148(6):2635-43. doi: 10.1210/en.2007-0270. Epub 2007 Mar 29.
van Bezooijen RL, ten Dijke P, Papapoulos SE, Lowik CW. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev. 2005 Jun;16(3):319-27. doi: 10.1016/j.cytogfr.2005.02.005.
Moester MJ, Papapoulos SE, Lowik CW, van Bezooijen RL. Sclerostin: current knowledge and future perspectives. Calcif Tissue Int. 2010 Aug;87(2):99-107. doi: 10.1007/s00223-010-9372-1. Epub 2010 May 15.
Morales-Santana S, Diez-Perez A, Olmos JM, Nogues X, Sosa M, Diaz-Curiel M, Perez-Castrillon JL, Perez-Cano R, Torrijos A, Jodar E, Rio LD, Caeiro-Rey JR, Reyes-Garcia R, Garcia-Fontana B, Gonzalez-Macias J, Munoz-Torres M. Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis. Maturitas. 2015 Dec;82(4):402-10. doi: 10.1016/j.maturitas.2015.08.007. Epub 2015 Aug 20.
Ardawi MS, Rouzi AA, Qari MH. Physical activity in relation to serum sclerostin, insulin-like growth factor-1, and bone turnover markers in healthy premenopausal women: a cross-sectional and a longitudinal study. J Clin Endocrinol Metab. 2012 Oct;97(10):3691-9. doi: 10.1210/jc.2011-3361. Epub 2012 Aug 3.
Vainionpaa A, Korpelainen R, Vaananen HK, Haapalahti J, Jamsa T, Leppaluoto J. Effect of impact exercise on bone metabolism. Osteoporos Int. 2009 Oct;20(10):1725-33. doi: 10.1007/s00198-009-0881-6. Epub 2009 Mar 5.
Other Identifiers
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41153
Identifier Type: -
Identifier Source: org_study_id
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