Skip to main content
Erschienen in: Osteoporosis International 10/2018

05.07.2018 | Original Article

Genetic variation in Wnt/β-catenin and ER signalling pathways in female and male elite dancers and its associations with low bone mineral density: a cross-section and longitudinal study

verfasst von: T. Amorim, C. Durães, J. C. Machado, G. S. Metsios, M. Wyon, J. Maia, A. D. Flouris, F. Marques, L. Nogueira, N. Adubeiro, Y. Koutedakis

Erschienen in: Osteoporosis International | Ausgabe 10/2018

Einloggen, um Zugang zu erhalten

Abstract

Summary

The association of genetic polymorphisms with low bone mineral density in elite athletes have not been considered previously. The present study found that bone mass phenotypes in elite and pre-elite dancers are related to genetic variants at the Wnt/β-catenin and ER pathways.

Introduction

Some athletes (e.g. gymnasts, dancers, swimmers) are at increased risk for low bone mineral density (BMD) which, if untreated, can lead to osteoporosis. To investigate the association of genetic polymorphisms in the oestrogen receptor (ER) and the Wnt/β-catenin signalling pathways with low BMD in elite and pre-elite dancers (impact sport athletes).

Methods

The study included three phases: (1) 151 elite and pre-elite dancers were screened for the presence of low BMD and traditional osteoporosis risk factors (low body weight, menstrual disturbances, low energy availability); (2) a genetic association study was conducted in 151 elite and pre-elite dancers and age- and sex- controls; (3) serum sclerostin was measured in 101 pre-elite dancers and age- and sex-matched controls within a 3-year period.

Results

Eighty dancers revealed low BMD: 56.3% had at least one traditional osteoporosis risk factor, whereas 28.6% did not display any risk factor (37.2% revealed traditional osteoporosis risk factors, but had normal BMD). Body weight, menstrual disturbances and energy availability did not fully predict bone mass acquisition. Instead, genetic polymorphisms in the ER and Wnt/β-catenin pathways were found to be risk factors for low BMD in elite dancers. Sclerostin was significantly increased in dancers compared to controls during the 3-year follow-up (p < 0.05).

Conclusions

Elite and pre-elite dancers demonstrate high prevalence of low BMD, which is likely related to genetic variants at the Wnt/β-catenin and ER pathways and not to factors usually associated with BMD in athletes (body weight, menstrual disturbances, energy deficiency).
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Kesavan C, Mohan S, Srivastava AK, Kapoor S, Wergedal JE, Yu H, Baylink DJ (2006) Identification of genetic loci that regulate bone adaptive response to mechanical loading in C57BL/6J and C3H/HeJ mice intercross. Bone 39:634–643PubMedCrossRef Kesavan C, Mohan S, Srivastava AK, Kapoor S, Wergedal JE, Yu H, Baylink DJ (2006) Identification of genetic loci that regulate bone adaptive response to mechanical loading in C57BL/6J and C3H/HeJ mice intercross. Bone 39:634–643PubMedCrossRef
3.
Zurück zum Zitat Xing W, Baylink D, Kesavan C, Hu Y, Kapoor S, Chadwick RB, Mohan S (2005) Global gene expression analysis in the bones reveals involvement of several novel genes and pathways in mediating an anabolic response of mechanical loading in mice. J Cell Biochem 96:1049–1060PubMedCrossRef Xing W, Baylink D, Kesavan C, Hu Y, Kapoor S, Chadwick RB, Mohan S (2005) Global gene expression analysis in the bones reveals involvement of several novel genes and pathways in mediating an anabolic response of mechanical loading in mice. J Cell Biochem 96:1049–1060PubMedCrossRef
4.
Zurück zum Zitat Suuriniemi M, Mahonen A, Kovanen V, Alén M, Lyytikäinen A, Wang Q, Kröger H, Cheng S (2004) Association between exercise and pubertal BMD is modulated by estrogen receptor alpha genotype. J Bone Miner Res 19:1758–1765PubMedCrossRef Suuriniemi M, Mahonen A, Kovanen V, Alén M, Lyytikäinen A, Wang Q, Kröger H, Cheng S (2004) Association between exercise and pubertal BMD is modulated by estrogen receptor alpha genotype. J Bone Miner Res 19:1758–1765PubMedCrossRef
7.
Zurück zum Zitat Liedert A, Wagner L, Seefried L, Ebert R, Jakob F, Ignatius A (2010) Estrogen receptor and Wnt signaling interact to regulate early gene expression in response to mechanical strain in osteoblastic cells. Biochem Biophys Res Commun Elsevier Inc 394:755–759PubMedCrossRef Liedert A, Wagner L, Seefried L, Ebert R, Jakob F, Ignatius A (2010) Estrogen receptor and Wnt signaling interact to regulate early gene expression in response to mechanical strain in osteoblastic cells. Biochem Biophys Res Commun Elsevier Inc 394:755–759PubMedCrossRef
8.
Zurück zum Zitat Amorim T, Koutedakis Y, Nevill A, Wyon M, Maia J, Machado JC, Marques F, Metsios GS, Flouris AD, Adubeiro N, Nogueira L, Dimitriou L (2017) Bone mineral density in vocational and professional ballet dancers. Osteoporis Int 28:2903–2912CrossRef Amorim T, Koutedakis Y, Nevill A, Wyon M, Maia J, Machado JC, Marques F, Metsios GS, Flouris AD, Adubeiro N, Nogueira L, Dimitriou L (2017) Bone mineral density in vocational and professional ballet dancers. Osteoporis Int 28:2903–2912CrossRef
9.
Zurück zum Zitat Scofield KL, Hecht S (2012) Bone health in endurance athletes. Curr Sports Med Rep 11:328–334PubMedCrossRef Scofield KL, Hecht S (2012) Bone health in endurance athletes. Curr Sports Med Rep 11:328–334PubMedCrossRef
10.
Zurück zum Zitat Pollock N, Grogan C, Perry M, Pedlar C, Cooke K, Morrissey D, Dimitriou L (2010) Bone-mineral density and other features of the female athlete triad in elite endurance runners: a longitudinal and cross-sectional observational study. Int J Sport Nutr Exerc Metab 20:418–426PubMedCrossRef Pollock N, Grogan C, Perry M, Pedlar C, Cooke K, Morrissey D, Dimitriou L (2010) Bone-mineral density and other features of the female athlete triad in elite endurance runners: a longitudinal and cross-sectional observational study. Int J Sport Nutr Exerc Metab 20:418–426PubMedCrossRef
11.
Zurück zum Zitat Xu J, Lombardi G, Jiao W, Banfi G (2016) Effects of exercise on bone status in female subjects, from young girls to postmenopausal women: an overview of systematic reviews and meta-analyses. Sports Med 46:1165–1182PubMedCrossRef Xu J, Lombardi G, Jiao W, Banfi G (2016) Effects of exercise on bone status in female subjects, from young girls to postmenopausal women: an overview of systematic reviews and meta-analyses. Sports Med 46:1165–1182PubMedCrossRef
12.
Zurück zum Zitat Guadalupe-Grau A, Fuentes T, Guerra B, Calbet JAL (2009) Exercise and bone mass in adults. Sport Med 39:439–468CrossRef Guadalupe-Grau A, Fuentes T, Guerra B, Calbet JAL (2009) Exercise and bone mass in adults. Sport Med 39:439–468CrossRef
14.
Zurück zum Zitat Nattiv A, Loucks AB, Manore MM, Sanborn CF, Sundgot-Borgen J, Warren MP (2007) The female athlete triad. Med Sci Sports Exerc 39:1867–1882PubMedCrossRef Nattiv A, Loucks AB, Manore MM, Sanborn CF, Sundgot-Borgen J, Warren MP (2007) The female athlete triad. Med Sci Sports Exerc 39:1867–1882PubMedCrossRef
15.
Zurück zum Zitat Gibbs JC, Williams NI, De Souza MJ (2013) Prevalence of individual and combined components of the female athlete triad. Med Sci Sports Exerc 45:985–996PubMedCrossRef Gibbs JC, Williams NI, De Souza MJ (2013) Prevalence of individual and combined components of the female athlete triad. Med Sci Sports Exerc 45:985–996PubMedCrossRef
16.
Zurück zum Zitat Torstveit MK, Sundgot-Borgen J (2005) The female athlete triad exists in both elite athletes and controls. Med Sci Sports Exerc 37:1449–1459PubMedCrossRef Torstveit MK, Sundgot-Borgen J (2005) The female athlete triad exists in both elite athletes and controls. Med Sci Sports Exerc 37:1449–1459PubMedCrossRef
17.
Zurück zum Zitat Georgopoulos N a, Markou KB, Theodoropoulou A, Vagenakis G e, Mylonas P, Vagenakis AG (2004) Growth, pubertal development, skeletal maturation and bone mass acquisition in athletes. Hormones 3:233–243PubMedCrossRef Georgopoulos N a, Markou KB, Theodoropoulou A, Vagenakis G e, Mylonas P, Vagenakis AG (2004) Growth, pubertal development, skeletal maturation and bone mass acquisition in athletes. Hormones 3:233–243PubMedCrossRef
19.
Zurück zum Zitat Bonjour JP, Chevalley T (2014) Pubertal timing, bone acquisition, and risk of fracture throughout life. Endocr Rev 35:820–847PubMedCrossRef Bonjour JP, Chevalley T (2014) Pubertal timing, bone acquisition, and risk of fracture throughout life. Endocr Rev 35:820–847PubMedCrossRef
20.
Zurück zum Zitat Di Pietro L, Stachenfeld N (2006) Refutation of the myth of the female athlete triad. Br J Sports Med 41:57–58CrossRef Di Pietro L, Stachenfeld N (2006) Refutation of the myth of the female athlete triad. Br J Sports Med 41:57–58CrossRef
21.
Zurück zum Zitat Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, Meyer N, Sherman R, Steffen K, Budgett R, Ljungqvist A (2014) The IOC consensus statement: beyond the female athlete triad—Relative Energy Deficiency in Sport (RED-S). Br J Sports Med 48:491–497PubMedCrossRef Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, Meyer N, Sherman R, Steffen K, Budgett R, Ljungqvist A (2014) The IOC consensus statement: beyond the female athlete triad—Relative Energy Deficiency in Sport (RED-S). Br J Sports Med 48:491–497PubMedCrossRef
22.
Zurück zum Zitat Kleposki RW (2002) The female athlete triad: a terrible trio implications for primary care. J Am Acad Nurse Pract 14:23–26 Kleposki RW (2002) The female athlete triad: a terrible trio implications for primary care. J Am Acad Nurse Pract 14:23–26
23.
Zurück zum Zitat George C, Leonard J, Hutchinson M (2011) The female athlete triad: a current concepts review. S Afr J Sport Med 23:50–56CrossRef George C, Leonard J, Hutchinson M (2011) The female athlete triad: a current concepts review. S Afr J Sport Med 23:50–56CrossRef
24.
Zurück zum Zitat Robinson TL, Snow-Harter C, Taaffe DR, Gillis D, Shaw J, Marcus R (1995) Gymnasts exhibit higher bone mass than runners despite similar prevalence of amenorrhea and oligomenorrhea. J Bone Miner Res 10:26–35PubMedCrossRef Robinson TL, Snow-Harter C, Taaffe DR, Gillis D, Shaw J, Marcus R (1995) Gymnasts exhibit higher bone mass than runners despite similar prevalence of amenorrhea and oligomenorrhea. J Bone Miner Res 10:26–35PubMedCrossRef
25.
Zurück zum Zitat Maïmoun L, Coste O, Mariano-Goulart D, Galtier F, Mura T, Philibert P, Briot K, Paris F, Sultan C (2011) In peripubertal girls, artistic gymnastics improves areal bone mineral density and femoral bone geometry without affecting serum OPG/RANKL levels. Osteoporos Int 22:3055–3066PubMedCrossRef Maïmoun L, Coste O, Mariano-Goulart D, Galtier F, Mura T, Philibert P, Briot K, Paris F, Sultan C (2011) In peripubertal girls, artistic gymnastics improves areal bone mineral density and femoral bone geometry without affecting serum OPG/RANKL levels. Osteoporos Int 22:3055–3066PubMedCrossRef
26.
Zurück zum Zitat Maïmoun L, Coste O, Philibert P, Briot K, Mura T, Galtier F et al (2013) Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry. Metabolism. Elsevier Inc 62:1088–1098PubMedCrossRef Maïmoun L, Coste O, Philibert P, Briot K, Mura T, Galtier F et al (2013) Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry. Metabolism. Elsevier Inc 62:1088–1098PubMedCrossRef
27.
Zurück zum Zitat Khan KM, Green RM, Saul A, Bennell KL, Crichton KJ, Hopper JL et al (1996) Retired elite female ballet dancers and nonathletic controls have similar bone mineral density at weightbearing sites. J Bone Miner Res 11:1566–1574PubMedCrossRef Khan KM, Green RM, Saul A, Bennell KL, Crichton KJ, Hopper JL et al (1996) Retired elite female ballet dancers and nonathletic controls have similar bone mineral density at weightbearing sites. J Bone Miner Res 11:1566–1574PubMedCrossRef
28.
Zurück zum Zitat Kirchner EM, Lewis RD, O’Connor PJ (1994) Bone mineral density and dietary intake of female college gymnasts. Med Sci Sport Exerc 27:543–549 Kirchner EM, Lewis RD, O’Connor PJ (1994) Bone mineral density and dietary intake of female college gymnasts. Med Sci Sport Exerc 27:543–549
29.
Zurück zum Zitat Twitchett EA, Koutedakis Y, Wyon MA (2009) Physiological fitness and professional classical ballet performance: a brief review. J Strength Cond Res 23:2732–2740PubMedCrossRef Twitchett EA, Koutedakis Y, Wyon MA (2009) Physiological fitness and professional classical ballet performance: a brief review. J Strength Cond Res 23:2732–2740PubMedCrossRef
30.
Zurück zum Zitat Twitchett E, Ph D, Brodrick A, Sc M, Nevill AM, Koutedakis Y et al (2010) Does physical fitness affect injury occurrence and time loss due to injury in elite vocational ballet students? J Dance Med Sci 14:26–31PubMed Twitchett E, Ph D, Brodrick A, Sc M, Nevill AM, Koutedakis Y et al (2010) Does physical fitness affect injury occurrence and time loss due to injury in elite vocational ballet students? J Dance Med Sci 14:26–31PubMed
31.
Zurück zum Zitat Li WF, Hou SX, Yu B, Li MM, Férec C, Chen JM (2010) Genetics of osteoporosis: accelerating pace in gene identification and validation. Hum Genet 127:249–285PubMedCrossRef Li WF, Hou SX, Yu B, Li MM, Férec C, Chen JM (2010) Genetics of osteoporosis: accelerating pace in gene identification and validation. Hum Genet 127:249–285PubMedCrossRef
32.
Zurück zum Zitat Crawford PB, Obarzanek E, Morrison J, Sabry ZI (1994) Comparative advantage of 3-day food records over 24-hour recall and 5-day food frequency validated by observation of 9- and 10-year-old girls. J Am Diet Assoc 94:626–630PubMedCrossRef Crawford PB, Obarzanek E, Morrison J, Sabry ZI (1994) Comparative advantage of 3-day food records over 24-hour recall and 5-day food frequency validated by observation of 9- and 10-year-old girls. J Am Diet Assoc 94:626–630PubMedCrossRef
33.
Zurück zum Zitat Brazeau AS, Beaudoin N, Bélisle V, Messier V, Karelis AD, Rabasa-Lhoret R (2016) Validation and reliability of two activity monitors for energy expenditure assessment. J Sci Med Sport 19:46–50PubMed Brazeau AS, Beaudoin N, Bélisle V, Messier V, Karelis AD, Rabasa-Lhoret R (2016) Validation and reliability of two activity monitors for energy expenditure assessment. J Sci Med Sport 19:46–50PubMed
34.
Zurück zum Zitat Amorim T (2017) Bone mass of female dance students prior to professional dance training: a cross-sectional study. PLoS One 12:1–11 Amorim T (2017) Bone mass of female dance students prior to professional dance training: a cross-sectional study. PLoS One 12:1–11
35.
Zurück zum Zitat Tu X, Rhee Y, Condon KW, Bivi N, Allen MR, Dwyer D et al (2012) Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone Elsevier BV 50:209–217PubMedCrossRef Tu X, Rhee Y, Condon KW, Bivi N, Allen MR, Dwyer D et al (2012) Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone Elsevier BV 50:209–217PubMedCrossRef
36.
Zurück zum Zitat Doyle-Lucas AF, Akers JD, Davy BM (2010) Energetic efficiency, menstrual irregularity, and bone mineral density in elite professional female ballet dancers. J Dance Med Sci 14:146–154PubMed Doyle-Lucas AF, Akers JD, Davy BM (2010) Energetic efficiency, menstrual irregularity, and bone mineral density in elite professional female ballet dancers. J Dance Med Sci 14:146–154PubMed
37.
Zurück zum Zitat Burckhardt P, Wynn E, Krieg M-A, Bagutti C, Faouzi M (2011) The effects of nutrition, puberty and dancing on bone density in adolescent ballet dancers. J Dance Med Sci 15:51–60PubMed Burckhardt P, Wynn E, Krieg M-A, Bagutti C, Faouzi M (2011) The effects of nutrition, puberty and dancing on bone density in adolescent ballet dancers. J Dance Med Sci 15:51–60PubMed
38.
Zurück zum Zitat Valentino R, Savastano S, Tommaselli AP, D’Amore G, Dorato M, Lombardi G (2001) The influence of intense ballet training on trabecular bone mass, hormone status, and gonadotropin structure in young women. J Clin Endocrinol Metab 86:4674–4678PubMedCrossRef Valentino R, Savastano S, Tommaselli AP, D’Amore G, Dorato M, Lombardi G (2001) The influence of intense ballet training on trabecular bone mass, hormone status, and gonadotropin structure in young women. J Clin Endocrinol Metab 86:4674–4678PubMedCrossRef
39.
Zurück zum Zitat Amorim T, Wyon M, Machado JC, Metsios GS, Flouris D, Koutedakis Y (2015) Prevalence of low bone mineral density in female dancers. Sport Med 45:257–268CrossRef Amorim T, Wyon M, Machado JC, Metsios GS, Flouris D, Koutedakis Y (2015) Prevalence of low bone mineral density in female dancers. Sport Med 45:257–268CrossRef
40.
Zurück zum Zitat Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ (2012) Update on Wnt signaling in bone cell biology and bone disease. Gene. Elsevier B.V. 492:1–18PubMedCrossRef Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ (2012) Update on Wnt signaling in bone cell biology and bone disease. Gene. Elsevier B.V. 492:1–18PubMedCrossRef
41.
Zurück zum Zitat Tobias JH (2003) At the crossroads of skeletal responses to estrogen and exercise. Trends Endocrinol Metab 14:441–443PubMedCrossRef Tobias JH (2003) At the crossroads of skeletal responses to estrogen and exercise. Trends Endocrinol Metab 14:441–443PubMedCrossRef
42.
Zurück zum Zitat Lee K, Lanyon L (2004) Mechanical loading influences bone mass through estrogen receptor alpha. Exerc Sport Sci Rev 32:64–68PubMedCrossRef Lee K, Lanyon L (2004) Mechanical loading influences bone mass through estrogen receptor alpha. Exerc Sport Sci Rev 32:64–68PubMedCrossRef
44.
Zurück zum Zitat Li H, Chen D, Zhang J (2012) Analysis of intron sequence features associated with transcriptional regulation in human genes. PLoS One 7:1–9 Li H, Chen D, Zhang J (2012) Analysis of intron sequence features associated with transcriptional regulation in human genes. PLoS One 7:1–9
45.
Zurück zum Zitat Majewski J, Majewski J, Ott J, Ott J (2002) Distribution and characterization of regulatory elements in the human genome. Genome Res 12:1827–1836PubMedPubMedCentralCrossRef Majewski J, Majewski J, Ott J, Ott J (2002) Distribution and characterization of regulatory elements in the human genome. Genome Res 12:1827–1836PubMedPubMedCentralCrossRef
46.
Zurück zum Zitat Nott A, Meislin SH, Moore MJ (2003) A quantitative analysis of intron effects on mammalian gene expression a quantitative analysis of intron effects on mammalian gene expression. RNA 9:607–617PubMedPubMedCentralCrossRef Nott A, Meislin SH, Moore MJ (2003) A quantitative analysis of intron effects on mammalian gene expression a quantitative analysis of intron effects on mammalian gene expression. RNA 9:607–617PubMedPubMedCentralCrossRef
47.
Zurück zum Zitat Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA (2003) Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 22:6267–6276PubMedPubMedCentralCrossRef Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA (2003) Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 22:6267–6276PubMedPubMedCentralCrossRef
49.
Zurück zum Zitat Ardawi M-SM, Rouzi AA, Qari MH (2012) 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 97:3691–3699PubMedCrossRef Ardawi M-SM, Rouzi AA, Qari MH (2012) 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 97:3691–3699PubMedCrossRef
50.
Zurück zum Zitat Braidman IP, Hainey L, Batra G, Selby PL, Saunders PT, J a H (2001) Localization of estrogen receptor beta protein expression in adult human bone. J Bone Miner Res 16:214–220PubMedCrossRef Braidman IP, Hainey L, Batra G, Selby PL, Saunders PT, J a H (2001) Localization of estrogen receptor beta protein expression in adult human bone. J Bone Miner Res 16:214–220PubMedCrossRef
Metadaten
Titel
Genetic variation in Wnt/β-catenin and ER signalling pathways in female and male elite dancers and its associations with low bone mineral density: a cross-section and longitudinal study
verfasst von
T. Amorim
C. Durães
J. C. Machado
G. S. Metsios
M. Wyon
J. Maia
A. D. Flouris
F. Marques
L. Nogueira
N. Adubeiro
Y. Koutedakis
Publikationsdatum
05.07.2018
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 10/2018
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-018-4610-x

Weitere Artikel der Ausgabe 10/2018

Osteoporosis International 10/2018 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.