Comparing the Effect of Bone-loading Exercises and Pulsed Electromagnetic Fields on Bone Turnover Markers in Women with Osteoporosis: A Randomized Clinical Trial Study Protocol

Document Type : PROTOCOL

Authors

1 Physical Therapy Department, School of Rehabilitation, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Rheumatology, Zanjan University of Medical Sciences, Zanjan, Iran

10.22038/abjs.2024.76983.3557

Abstract

Objective: Given the bone sensitivity to mechanical stimulus, bone-loading exercises and applying the Pulsed 
Electromagnetic Fields (PEMF(s)) are recommended for promoting bone strength. In this context, these two 
interventions 's effect on bone turnover markers (BTMs) in osteoporosis patients is yet to be clarified; consequently, 
an attempt is made in this study to compare the effect of these two interventions on bone turnover markers in women 
with Postmenopausal Osteoporosis (PMOP).
Methods: This study is design as a randomized, single-center, three-arms, controlled trial. A total of 51 women with 
PMOP will be randomly assigned to three groups of 17, using opaque, sealed envelopes containing labels for A, B, 
and C groups. Group A) will receive bone-loading exercises, B) will follow the PEMF(s) and C) will be exposed to 
the combination of A and B. These three groups will require intervention for 24 sessions (2 sessions/week) next to 
their routine medical treatment (Alendronate+ Calcium+ Vitamin D). The primary outcome of this study is the serum 
biomarker of bone formation (bone-specific alkaline phosphatase, BSALP) and resorption (N-terminal telopeptide, 
NTX). The secondary outcomes consist of thoracic kyphosis angle, fear of falling, and quality of life. The outcomes 
are measured three times: at baseline, after 24 sessions of intervention, and at 12 weeks follow-up. A primary 
outcome will be measured and reported by a laboratory expert who is blinded to the participant grouping. 
Result: The trial has the code of ethics for research (IR.TUMS.FNM.REC.1401.126) and the code of Iranian Registry 
of Clinical Trials (IRCT) (IRCT20221202056687N1). Study results are expected to be available by mid-2024.
Conclusion: This trial will provide new practical knowledge on the bone-loading exercises and PEMFS(s)’s effect 
on PMOP women. This knowledge is of the essence for physiotherapists, clinicians, other healthcare professionals, 
and policymakers in the healthcare system. 
Level of evidence: Not applicable

Keywords

Main Subjects


1. Waltman N, Kupzyk KA, Flores LE, Mack LR, Lappe JM, Bilek 
LD. Bone-loading exercises versus risedronate for the 
prevention of osteoporosis in postmenopausal women with 
low bone mass: A randomized controlled trial. Osteoporos 
Int. 2022;33(2):475-486. doi: 10.1007/s00198-021-06083-2.
2. Kanis JA, McCloskey EV, Harvey NC, et al. The need to 
distinguish intervention thresholds and diagnostic thresholds 
in the management of osteoporosis. Osteoporos Int. 2023; 
34(1):1-9. doi: 10.1007/s00198-022-06567-9. 
3. Johnell O, Kanis J, Oden A, et al. Mortality after osteoporotic 
fractures. Osteoporos Int. 2004; 15(1):38-42. doi: 
10.1007/s00198-003-1490-4. 
4. Nazrun AS, Tzar MN, Mokhtar SA, Mohamed IN. A systematic 
review of the outcomes of osteoporotic fracture patients after 
hospital discharge: morbidity, subsequent fractures, and 
mortality. Ther Clin Risk Manag.2014:10:937-48. doi: 
10.2147/TCRM.S72456. 
5. Black DM, Rosen CJ. Postmenopausal osteoporosis. N Engl J 
Med.2016; 374(3):254-62. doi: 10.1056/NEJMcp1513724.
6. Cranney A, Tugwell P, Adachi J, et al. Meta-analyses of therapies 
for postmenopausal osteoporosis. III. Meta-analysis of 
risedronate for the treatment of postmenopausal 
osteoporosis. Endocr Rev.2002; 23(4):517-23. doi: 
10.1210/er.2001-3002.
7. Sambrook PN, Cameron ID, Chen JS, et al. Influence of fall 
related factors and bone strength on fracture risk in the frail 
elderly. Osteoporos Int. 2007; 18(5):603-10. doi: 
10.1007/s00198-006-0290-z. 
8. Bilek LD, Waltman NL, Lappe JM, et al. Protocol for a 
randomized controlled trial to compare bone-loading 
exercises with risedronate for preventing bone loss in 
osteopenic postmenopausal women. Article. BMC Womens 
Health.2016; 16(1):59. doi: 10.1186/s12905-016-0339-x.
9. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, 
Reginster J-Y. European guidance for the diagnosis and 
management of osteoporosis in postmenopausal women. 
Osteoporos Int. 2013; 24(1):23-57. doi: 10.1007/s00198-
012-2074-y.
10. Watson S, Weeks B, Weis L, Harding A, Horan S, Beck B. Highintensity exercise did not cause vertebral fractures and 
improves thoracic kyphosis in postmenopausal women with 
low to very low bone mass: the LIFTMOR trial. J Bone Miner 
Res.2018; 33(2):211-220. doi: 10.1002/jbmr.3284.
11. 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; 
43(12):898-908. doi: 10.1136/bjsm.2008.052704. 
12. Howe TE, Shea B, Dawson LJ, et al. Exercise for preventing 
and treating osteoporosis in postmenopausal women. 
Cochrane Database Syst Rev. 2011 :( 7):CD000333. doi: 
10.1002/14651858.CD000333.pub2.
13. Parhampour B, Torkaman G, Hoorfar H, Hedayati M, 
Ravanbod R. Effects of short-term resistance training and 
pulsed electromagnetic fields on bone metabolism and joint 
function in severe haemophilia A patients with osteoporosis: 
a randomized controlled trial. Clin Rehabil. 2014; 28(5):440-
50. doi: 10.1177/0269215513505299.
14. Giordano N, Battisti E, Geraci S, et al. Effect of electromagnetic 
fields on bone mineral density and biochemical markers of 
bone turnover in osteoporosis: a single-blind, randomized 
pilot study. Current Therapeutic Research. 2001; 62(3):187-
193. doi:10.1016/S0011-393X(01)80030-8. 
15. Mosti MP, Kaehler N, Stunes AK, Hoff J, Syversen U. Maximal 
strength training in postmenopausal women with 
osteoporosis or osteopenia. J Strength Cond Res.2013; 
27(10):2879-86. doi: 10.1519/JSC.0b013e318280d4e2. 
16. Veiskarami M, Aminian G, Bahramizadeh M, Gholami M, 
Ebrahimzadeh F, Arazpour M. The Efficacy of “Anatomical 
Posture Control Orthosis” on the Activity of Erector spinae 
Muscle, Risk of Falling, Balance Confidence, and Walking 
Speed in Osteoporotic Hyperkyphotic Subjects. Arch Bone Jt 
Surg.2022; 10(9):798-805. doi: 
10.22038/ABJS.2021.53771.2678.
17. Abourazzak FE, Allali F, Rostom S, et al. Factors influencing 
quality of life in Moroccan postmenopausal women with 
osteoporotic vertebral fracture assessed by ECOS 16 
questionnaire. Health Qual Life Outcomes. 2009:7:23. doi: 
10.1186/1477-7525-7-23. 
18. Shariatzadeh H, Modaghegh BS, Mirzaei A. The effect of 
dynamic hyperextension brace on osteoporosis and hyperkyphosis reduction in postmenopausal osteoporotic 
women. Arch Bone Jt Surg.2017; 5(3):181-185.1.doi: 
0.22038/ABJS.2017.20826.1539. 
19. Sangtarash F, Manshadi F, Sadeghi A. The relationship of 
thoracic kyphosis to gait performance and quality of life in 
women with osteoporosis. Osteoporos Int. 2015; 26(8):2203-
8. doi: 10.1007/s00198-015-3143-9. 
20. 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. 
21. Rezaei N, Torkaman G, Movasseghe S, Hedayati M, Bayat N. 
The comparison of 6-week resistance training and pulsed 
electromagnetic field on TALP, Ca, P, cortisol, and anthropometric 
parameters in osteoporotic postmenopausal women. 2012: 
20193163173. https://doi.org/10.1007/s11332-022-01018-
8.
22. Funk RH, Monsees T, Özkucur N. Electromagnetic effects–
From cell biology to medicine. Progress in histochemistry and 
cytochemistry. Prog Histochem Cytochem.2009; 43(4):177-
264. doi: 10.1016/j.proghi.2008.07.001. 
23. Sun LY, Hsieh DK, Yu TC, et al. Effect of pulsed 
electromagnetic field on the proliferation and differentiation 
potential of human bone marrow mesenchymal stem cells. 
Bioelectromagnetics. 2009; 30(4):251-60. doi: 
10.1002/bem.20472.
24. Eid MM, El-Gendy AM, Abdelbasset WK, Elkholi SM, AbdelFattah MS. The effect of magnetic therapy and moderate 
aerobic exercise on osteoporotic patients: A randomized 
clinical study. Medicine (Baltimore).2021; 100(39):e27379. 
doi: 10.1097/MD.0000000000027379.
25. Greenblatt MB, Tsai JN, Wein MN. Bone turnover markers in 
the diagnosis and monitoring of metabolic bone disease. Clin 
Chem. 2017; 63(2):464-474. doi: 
10.1373/clinchem.2016.259085. 
26. Keshavarzi F, Azadinia F, Talebian S, Rasouli O. Test-retest 
reliability of a load cell setup, Ito, and timed loaded standing 
tests for measuring muscle strength and endurance in older 
adults with and without hyperkyphosis. Musculoskelet Sci 
Pract.2022:58:102475. doi: 10.1016/j.msksp.2021.102475. 
27. Azadinia F, Kamyab M, Behtash H, Ganjavian MS, Javaheri MR. 
The validity and reliability of non-invasive methods for 
measuring kyphosis. J Spinal Disord Tech. 2014; 27(6):E212-
8. doi: 10.1097/BSD.0b013e31829a3574.
28. Azadinia F, Hosseinabadi M, Ebrahimi I, et al. Validity and 
test–retest reliability of photogrammetry in adolescents with 
hyperkyphosis. Physiother Theory Pract.2022; 38(13):3018-
3026. doi: 10.1080/09593985.2021.1975337. 
29. Mosallanezhad Z, Salavati M, Hellström K, Reza Sotoudeh G, 
Nilsson Wikmar L, Frändin K. Cross-cultural adaptation, 
reliability and validity of the Persian version of the modified 
falls efficacy scale. Disabil Rehabil. 2011; 33(25-26):2446-53. 
doi: 10.3109/09638288.2011.574774. 
30. Lee Y-K, Kim H-J, Park JW, et al. Transcultural adaptation and 
psychometric properties of the Korean version of the Quality 
of Life Questionnaire of the European Foundation for 
Osteoporosis (QUALEFFO-41). Arch Osteoporos.2019; 
14(1):96. doi: 10.1007/s11657-019-0647-5.
31. Azimi P, Shahzadi S, Azhari S, Montazeri A. An outcome 
measure of functionality and quality of life in Iranian women 
with osteoporotic vertebral fractures: a validation study of 
the QUALEFFO-41. J Orthop Sci. 2014; 19(6):860-7. doi: 
10.1007/s00776-014-0609-0. 
32. Stanghelle B, Bentzen H, Giangregorio L, Pripp AH, Skelton 
DA, Bergland A. Physical fitness in older women with 
osteoporosis and vertebral fracture after a resistance and 
balance exercise programme: 3-month post-intervention 
follow-up of a randomised controlled trial. BMC 
Musculoskelet Disord.2020; 21(1):471. doi: 10.1186/s12891-
020-03495-9.
33. Holubiac IȘ, Leuciuc FV, Crăciun DM, Dobrescu T. Effect of 
Strength Training Protocol on Bone Mineral Density for 
Postmenopausal Women with Osteopenia/Osteoporosis 
Assessed by Dual-Energy X-ray Absorptiometry (DEXA). 
Sensors (Basel).2022; 22(5):1904. doi: 10.3390/s22051904. 
34. Giusti A, Giovale M, Ponte M, et al. Short-term effect of lowintensity, pulsed, electromagnetic fields on gait 
characteristics in older adults with low bone mineral density: 
A pilot randomized-controlled trial. Geriatr Gerontol 
Int.2013; 13(2):393-7. doi: 10.1111/j.1447-
0594.2012.00915.x. 
35. Turner CH, Robling AG. Designing exercise regimens to 
increase bone strength. Exerc Sport Sci Rev.2003; 31(1):45-
50. doi: 10.1097/00003677-200301000-00009. 
36. Roghani T, Torkaman G, Movasseghe S, Hedayati M, Goosheh 
B, Bayat N. Effects of short-term aerobic exercise with and 
without external loading on bone metabolism and balance in 
postmenopausal women with osteoporosis. Rheumatol 
Int.2013; 33(2):291-8. doi: 10.1007/s00296-012-2388-2. 
37. Olsen C, Bergland A. The effect of exercise and education on 
fear of falling in elderly women with osteoporosis and a 
history of vertebral fracture: results of a randomized 
controlled trial. Osteoporos Int.2014; 25(8):2017-25. doi: 
10.1007/s00198-014-2724-3. 
38. Delbaere K, Van den Noortgate N, Bourgois J, Vanderstraeten 
G, Tine W, Cambier D. The Physical Performance Test as a 
predictor of frequent fallers: a prospective community-based 
cohort study. Clin Rehabil.2006; 20(1):83-90. doi: 
10.1191/0269215506cr885oa.a.