Skip to main content
Erschienen in: Osteoporosis International 7/2021

13.01.2021 | Original Article

Estimates of the effects of physical activity on osteoporosis using multivariable Mendelian randomization analysis

verfasst von: F. Xu, Q. Zhang, L.-K. Wang, Q.-X. Tang, C.-Q. Sun, H.-W. Deng

Erschienen in: Osteoporosis International | Ausgabe 7/2021

Einloggen, um Zugang zu erhalten

Abstract

Summary

This study estimates causality of physical activity (PA) on bone mineral density (BMD) by conducting multivariable Mendelian randomization (MR). The findings suggest that habitual vigorous PA increases lumbar spine BMD, and higher overall acceleration average would improve forearm BMD. The results could promote PA intervention targeting individuals with optimized type.

Introduction

Evidence from epidemiologic studies showed type, frequency, and duration of PA influenced BMD. However, these observational studies may be confounded by many factors, resulting in spurious associations. We aimed to conduct multivariable MR to estimate the causal effect of self-reported and device-measured PA on osteoporosis.

Methods

Three self-reported and two device-measured PA-related traits were selected as exposures. Outcomes were BMD at different skeletal sites: femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD). Exposure datasets were obtained from UK Biobank with total 377,234 subjects. Outcome datasets were obtained from GEFOS consortium with 53,236 subjects. Standard MR analysis and multivariable MR were conducted to assess the total and direct causal effect of PA on BMD.

Results

For self-reported PA, inverse-normalized moderate-to-vigorous had a direct causal effect on FN BMD independently (β = − 1.116 (95% confidence interval, 95%CI: − 2.210, − 0.023), P = 0.045); vigorous PA showed a direct effect (β = 3.592 (95%CI: 0.310, 6.874), P = 0.032) on LS BMD independently. While overall acceleration average and fraction of accelerations both had a direct causal effect on FA BMD independently.

Conclusions

Habitual vigorous PA could increase LS BMD. Individuals with higher overall acceleration average would have a higher FA BMD.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Compston JE, McClung MR, Leslie WD (2019) Osteoporosis. Lancet 393:364–376CrossRef Compston JE, McClung MR, Leslie WD (2019) Osteoporosis. Lancet 393:364–376CrossRef
2.
Zurück zum Zitat Papadimitriou N, Tsilidis KK, Orfanos P, Benetou V, Ntzani EE, Soerjomataram I, Künn-Nelen A, Pettersson-Kymmer U, Eriksson S, Brenner H, Schöttker B, Saum KU, Holleczek B, Grodstein FD, Feskanich D, Orsini N, Wolk A, Bellavia A, Wilsgaard T, Jørgensen L, Boffetta P, Trichopoulos D, Trichopoulou A (2017) Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium. Lancet Public Health 2:e239–e246CrossRef Papadimitriou N, Tsilidis KK, Orfanos P, Benetou V, Ntzani EE, Soerjomataram I, Künn-Nelen A, Pettersson-Kymmer U, Eriksson S, Brenner H, Schöttker B, Saum KU, Holleczek B, Grodstein FD, Feskanich D, Orsini N, Wolk A, Bellavia A, Wilsgaard T, Jørgensen L, Boffetta P, Trichopoulos D, Trichopoulou A (2017) Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium. Lancet Public Health 2:e239–e246CrossRef
3.
Zurück zum Zitat Blume SW, Curtis JR (2011) Medical costs of osteoporosis in the elderly Medicare population. Osteoporos Int 22:1835–1844CrossRef Blume SW, Curtis JR (2011) Medical costs of osteoporosis in the elderly Medicare population. Osteoporos Int 22:1835–1844CrossRef
4.
Zurück zum Zitat Alghadir AH, Gabr SA, Al-Eisa E (2015) Physical activity and lifestyle effects on bone mineral density among young adults: sociodemographic and biochemical analysis. J Phys Ther Sci 27:2261–2270CrossRef Alghadir AH, Gabr SA, Al-Eisa E (2015) Physical activity and lifestyle effects on bone mineral density among young adults: sociodemographic and biochemical analysis. J Phys Ther Sci 27:2261–2270CrossRef
5.
Zurück zum Zitat Amiri AM, Hosseini SR, Rahmaninia F, Nooreddini H, Bijani A (2015) Relationship between bone mineral density and physical activity level in the elderly. Ann Appl Sport Sci 3:23–32CrossRef Amiri AM, Hosseini SR, Rahmaninia F, Nooreddini H, Bijani A (2015) Relationship between bone mineral density and physical activity level in the elderly. Ann Appl Sport Sci 3:23–32CrossRef
6.
Zurück zum Zitat Lin J, Chen L, Ni S, Ru Y, Ye S, Fu X, Gan D, Li J, Zhang L, Han S, Zhu S (2019) Association between sleep quality and bone mineral density in Chinese women vary by age and menopausal status. Sleep Med 53:75–80CrossRef Lin J, Chen L, Ni S, Ru Y, Ye S, Fu X, Gan D, Li J, Zhang L, Han S, Zhu S (2019) Association between sleep quality and bone mineral density in Chinese women vary by age and menopausal status. Sleep Med 53:75–80CrossRef
7.
Zurück zum Zitat Meng XH, Tan LJ, Xiao HM, Tang BS, Deng HW (2019) Examining the causal role of leptin in bone mineral density: a Mendelian randomization study. Bone 125:25–29CrossRef Meng XH, Tan LJ, Xiao HM, Tang BS, Deng HW (2019) Examining the causal role of leptin in bone mineral density: a Mendelian randomization study. Bone 125:25–29CrossRef
8.
Zurück zum Zitat Bauman AE, Reis RS, Sallis JF, Wells JC, Loos RJ, Martin BW (2012) Correlates of physical activity: why are some people physically active and others not? Lancet 380:258–271CrossRef Bauman AE, Reis RS, Sallis JF, Wells JC, Loos RJ, Martin BW (2012) Correlates of physical activity: why are some people physically active and others not? Lancet 380:258–271CrossRef
9.
Zurück zum Zitat Marin-Puyalto J, Maestu J, Gomez-Cabello A, Latt E, Remmel L, Purge P, Vicente-Rodriguez G, Jurimae J (2019) Frequency and duration of vigorous physical activity bouts are associated with adolescent boys' bone mineral status: a cross-sectional study. Bone 120:141–147CrossRef Marin-Puyalto J, Maestu J, Gomez-Cabello A, Latt E, Remmel L, Purge P, Vicente-Rodriguez G, Jurimae J (2019) Frequency and duration of vigorous physical activity bouts are associated with adolescent boys' bone mineral status: a cross-sectional study. Bone 120:141–147CrossRef
10.
Zurück zum Zitat Davey Smith G, Hemani G (2014) Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet 23:R89–R98CrossRef Davey Smith G, Hemani G (2014) Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet 23:R89–R98CrossRef
11.
Zurück zum Zitat Burgess S, Thompson SG (2015) Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol 181:251–260CrossRef Burgess S, Thompson SG (2015) Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol 181:251–260CrossRef
12.
Zurück zum Zitat Sanderson E, Davey Smith G, Windmeijer F, Bowden J (2019) An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. Int J Epidemiol 48:713-727 Sanderson E, Davey Smith G, Windmeijer F, Bowden J (2019) An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. Int J Epidemiol 48:713-727
13.
Zurück zum Zitat Burgess S, Thompson DJ, Rees JMB, Day FR, Perry JR, Ong KK (2017) Dissecting causal pathways using Mendelian randomization with summarized genetic data: application to age at menarche and risk of breast cancer. Genetics 207:481–487CrossRef Burgess S, Thompson DJ, Rees JMB, Day FR, Perry JR, Ong KK (2017) Dissecting causal pathways using Mendelian randomization with summarized genetic data: application to age at menarche and risk of breast cancer. Genetics 207:481–487CrossRef
14.
Zurück zum Zitat Relton CL, Davey Smith G (2012) Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int J Epidemiol 41:161–176CrossRef Relton CL, Davey Smith G (2012) Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int J Epidemiol 41:161–176CrossRef
15.
Zurück zum Zitat Bull FC, Maslin TS, Armstrong T (2009) Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Health 6:790–804CrossRef Bull FC, Maslin TS, Armstrong T (2009) Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Health 6:790–804CrossRef
16.
Zurück zum Zitat Rowlands AV, Mirkes EM, Yates T, Clemes S, Davies M, Khunti K, Edwardson CL (2018) Accelerometer-assessed physical activity in epidemiology: are monitors equivalent? Med Sci Sports Exerc 50:257–265CrossRef Rowlands AV, Mirkes EM, Yates T, Clemes S, Davies M, Khunti K, Edwardson CL (2018) Accelerometer-assessed physical activity in epidemiology: are monitors equivalent? Med Sci Sports Exerc 50:257–265CrossRef
17.
Zurück zum Zitat Klimentidis YC, Raichlen DA, Bea J, Garcia DO, Wineinger NE, Mandarino LJ, Alexander GE, Chen Z, Going SB (2018) Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. Int J Obes 42:1161–1176CrossRef Klimentidis YC, Raichlen DA, Bea J, Garcia DO, Wineinger NE, Mandarino LJ, Alexander GE, Chen Z, Going SB (2018) Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. Int J Obes 42:1161–1176CrossRef
18.
Zurück zum Zitat Craig CL, Marshall AL, Sjostrom M et al (2003) International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35:1381–1395CrossRef Craig CL, Marshall AL, Sjostrom M et al (2003) International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35:1381–1395CrossRef
19.
Zurück zum Zitat Ekelund U, Sepp H, Brage S, Becker W, Jakes R, Hennings M, Wareham NJ (2006) Criterion-related validity of the last 7-day, short form of the International Physical Activity Questionnaire in Swedish adults. Public Health Nutr 9:258–265CrossRef Ekelund U, Sepp H, Brage S, Becker W, Jakes R, Hennings M, Wareham NJ (2006) Criterion-related validity of the last 7-day, short form of the International Physical Activity Questionnaire in Swedish adults. Public Health Nutr 9:258–265CrossRef
20.
Zurück zum Zitat Zheng HF, Forgetta V, Hsu YH et al (2015) Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature 526:112–117CrossRef Zheng HF, Forgetta V, Hsu YH et al (2015) Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature 526:112–117CrossRef
21.
Zurück zum Zitat Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44:512–525CrossRef Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44:512–525CrossRef
22.
Zurück zum Zitat Burgess S, Dudbridge F, Thompson SG (2016) Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods. Stat Med 35:1880–1906CrossRef Burgess S, Dudbridge F, Thompson SG (2016) Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods. Stat Med 35:1880–1906CrossRef
23.
Zurück zum Zitat Bowden J, Davey Smith G, Haycock PC, Burgess S (2016) Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol 40:304–314CrossRef Bowden J, Davey Smith G, Haycock PC, Burgess S (2016) Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol 40:304–314CrossRef
24.
Zurück zum Zitat Daly RM, Dalla Via J, Duckham RL, Fraser SF, Helge EW (2019) Exercise for the prevention of osteoporosis in postmenopausal women: an evidence-based guide to the optimal prescription. Braz J Phys Ther 23:170–180CrossRef Daly RM, Dalla Via J, Duckham RL, Fraser SF, Helge EW (2019) Exercise for the prevention of osteoporosis in postmenopausal women: an evidence-based guide to the optimal prescription. Braz J Phys Ther 23:170–180CrossRef
25.
Zurück zum Zitat Segev D, Hellerstein D, Dunsky A (2018) Physical activity-does it really increase bone density in postmenopausal women? A review of articles published between 2001-2016. Curr Aging Sci 11:4–9CrossRef Segev D, Hellerstein D, Dunsky A (2018) Physical activity-does it really increase bone density in postmenopausal women? A review of articles published between 2001-2016. Curr Aging Sci 11:4–9CrossRef
26.
Zurück zum Zitat Benedetti MG, Furlini G, Zati A, Letizia Mauro G (2018) The effectiveness of physical exercise on bone density in osteoporotic patients. Biomed Res Int 2018:4840531CrossRef Benedetti MG, Furlini G, Zati A, Letizia Mauro G (2018) The effectiveness of physical exercise on bone density in osteoporotic patients. Biomed Res Int 2018:4840531CrossRef
27.
Zurück zum Zitat Rubin CT, Rubin J, Judex S (2013) Exercise and the prevention of osteoporosis. In: C.J. Rosen (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, Wiley, Hoboken, pp 396–402 Rubin CT, Rubin J, Judex S (2013) Exercise and the prevention of osteoporosis. In: C.J. Rosen (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, Wiley, Hoboken, pp 396–402
28.
Zurück zum Zitat Klein-Nulend J, Bacabac RG, Bakker AD (2012) Mechanical loading and how it affects bone cells: the role of the osteocyte cytoskeleton in maintaining our skeleton. Eur Cell Mater 24:278–291CrossRef Klein-Nulend J, Bacabac RG, Bakker AD (2012) Mechanical loading and how it affects bone cells: the role of the osteocyte cytoskeleton in maintaining our skeleton. Eur Cell Mater 24:278–291CrossRef
29.
Zurück zum Zitat Forwood MR (2001) Mechanical effects on the skeleton: are there clinical implications? Osteoporos Int 12:77–83CrossRef Forwood MR (2001) Mechanical effects on the skeleton: are there clinical implications? Osteoporos Int 12:77–83CrossRef
30.
Zurück zum Zitat Duncan RL, Turner CH (1995) Mechanotransduction and the functional response of bone to mechanical strain. Calcif Tissue Int 57:344–358CrossRef Duncan RL, Turner CH (1995) Mechanotransduction and the functional response of bone to mechanical strain. Calcif Tissue Int 57:344–358CrossRef
31.
Zurück zum Zitat Wang Y, Xu D (2017) Effects of aerobic exercise on lipids and lipoproteins. Lipids Health Dis 16:132–132CrossRef Wang Y, Xu D (2017) Effects of aerobic exercise on lipids and lipoproteins. Lipids Health Dis 16:132–132CrossRef
32.
Zurück zum Zitat Wang Y, Si S, Liu J, Wang Z, Jia H, Feng K, Sun L, Song SJ (2016) The associations of serum lipids with vitamin D status. PLoS One 11:e0165157CrossRef Wang Y, Si S, Liu J, Wang Z, Jia H, Feng K, Sun L, Song SJ (2016) The associations of serum lipids with vitamin D status. PLoS One 11:e0165157CrossRef
33.
Zurück zum Zitat Scott D, Johansson J, McMillan LB, Ebeling PR, Nordstrom A, Nordstrom P (2019) Mid-calf skeletal muscle density and its associations with physical activity, bone health and incident 12-month falls in older adults: the healthy ageing initiative. Bone 120:446–451CrossRef Scott D, Johansson J, McMillan LB, Ebeling PR, Nordstrom A, Nordstrom P (2019) Mid-calf skeletal muscle density and its associations with physical activity, bone health and incident 12-month falls in older adults: the healthy ageing initiative. Bone 120:446–451CrossRef
34.
Zurück zum Zitat Zymbal V, Baptista F, Letuchy EM, Janz KF, Levy SM (2019) Mediating effect of muscle on the relationship of physical activity and bone. Med Sci Sports Exerc 51:202–210CrossRef Zymbal V, Baptista F, Letuchy EM, Janz KF, Levy SM (2019) Mediating effect of muscle on the relationship of physical activity and bone. Med Sci Sports Exerc 51:202–210CrossRef
35.
Zurück zum Zitat Muir JM, Ye C, Bhandari M, Adachi JD, Thabane L (2013) The effect of regular physical activity on bone mineral density in post-menopausal women aged 75 and over: a retrospective analysis from the Canadian multicentre osteoporosis study. BMC Musculoskelet Disord 14:253CrossRef Muir JM, Ye C, Bhandari M, Adachi JD, Thabane L (2013) The effect of regular physical activity on bone mineral density in post-menopausal women aged 75 and over: a retrospective analysis from the Canadian multicentre osteoporosis study. BMC Musculoskelet Disord 14:253CrossRef
36.
Zurück zum Zitat Mendez-Gallegos E, Caire-Juvera G, Astiazaran-Garcia H, Mendez-Estrada RO (2018) Comparison of measurements of bone mineral density in young and middle-aged adult women in relation to dietary, anthropometric and reproductive variables. Nutrients 10:1669 Mendez-Gallegos E, Caire-Juvera G, Astiazaran-Garcia H, Mendez-Estrada RO (2018) Comparison of measurements of bone mineral density in young and middle-aged adult women in relation to dietary, anthropometric and reproductive variables. Nutrients 10:1669
37.
Zurück zum Zitat Watson S, Weeks B, Weis L, Harding A, Horan S, Beck B (2019) 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 34:572CrossRef Watson S, Weeks B, Weis L, Harding A, Horan S, Beck B (2019) 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 34:572CrossRef
38.
Zurück zum Zitat Marques EA, Mota J, Carvalho J (2012) Exercise effects on bone mineral density in older adults: a meta-analysis of randomized controlled trials. Age (Dordr) 34:1493–1515CrossRef Marques EA, Mota J, Carvalho J (2012) Exercise effects on bone mineral density in older adults: a meta-analysis of randomized controlled trials. Age (Dordr) 34:1493–1515CrossRef
39.
Zurück zum Zitat Burgess S, Butterworth A, Thompson SG (2013) Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol 37:658–665CrossRef Burgess S, Butterworth A, Thompson SG (2013) Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol 37:658–665CrossRef
40.
Zurück zum Zitat Burgess S, Freitag DF, Khan H, Gorman DN, Thompson SG (2014) Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. PLoS One 9:e108891CrossRef Burgess S, Freitag DF, Khan H, Gorman DN, Thompson SG (2014) Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. PLoS One 9:e108891CrossRef
Metadaten
Titel
Estimates of the effects of physical activity on osteoporosis using multivariable Mendelian randomization analysis
verfasst von
F. Xu
Q. Zhang
L.-K. Wang
Q.-X. Tang
C.-Q. Sun
H.-W. Deng
Publikationsdatum
13.01.2021
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 7/2021
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-020-05786-2

Weitere Artikel der Ausgabe 7/2021

Osteoporosis International 7/2021 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.