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Licensed Unlicensed Requires Authentication Published by De Gruyter April 12, 2021

Serum sclerostin concentration is associated with specific adipose, muscle and bone tissue markers in lean adolescent females with increased physical activity

  • Jaak Jürimäe EMAIL logo , Vita Karvelyte , Liina Remmel , Anna-Liisa Tamm , Priit Purge , Rita Gruodyte-Raciene , Sigitas Kamandulis , Katre Maasalu , Luis Gracia-Marco and Vallo Tillmann

Abstract

Objectives

Sclerostin is an important regulator of bone mass involving the Wnt/β-catenin signalling pathway. Relatively few studies have investigated the relationships of circulating sclerostin levels with adiposity-related and muscle-related biochemical factors in individuals with increased energy metabolism. The aim of this study was to investigate the associations of circulating sclerostin with adipokines, myokines, osteokines and body composition values in lean adolescent females with increased physical activity.

Methods

A total of 73 adolescent females who were physically active and aged 14–18 years old participated in the study. Sclerostin, leptin, resistin, tumour necrosis factor (TNF)-α, interleukin (IL)-6, irisin, osteocalcin, C-terminal telopeptide of type I collagen (CTx), insulin-like growth factor (IGF)-1 and insulin were obtained from fasting blood samples. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and analyzed for body fat mass, lean body mass, bone mineral content and muscle mass.

Results

Serum sclerostin (117.9 ± 60.3 pg/mL) was correlated with age, age at menarche, body fat, muscle mass, training activity, leptin, TNF-α, irisin, osteocalcin, CTx and IGF-1. Multivariate linear regression analysis demonstrated that fat mass (β = 0.434; p = 0.001), leptin (β = −0.308; p = 0.015), irisin (β = 0.227; p = 0.024) and CTx (β = 0.290; p = 0.031) were the most important predictors of serum sclerostin concentration.

Conclusions

Bone-derived sclerostin is associated with specific adipokine, myokine and osteokine values in lean adolescent females with increased physical activity. These results suggest that the interactions between bone, adipose and muscle tissues could also be associated with circulating sclerostin concentrations.


Corresponding author: Professor Jaak Jürimäe, PhD, Institute of Sport Sciences and Physiotherapy, Faculty of Medicine, University of Tartu, 18. Ülikooli St., Tartu50090, Estonia, Phone: +372 7 376276, E-mail:

Funding source: Estonian Ministry of Education and Science

Award Identifier / Grant number: PRG 1120

Funding source: “La Caixa” Foundation

Award Identifier / Grant number: ID 100010434

Acknowledgments

We would like to thank all subjects participating in our study.

  1. Research funding: This study was supported by the Estonian Ministry of Education and Science (Grant PRG 1120). LGM is funded by “La Caixa” Foundation within the Junior Leader fellowship programme (ID 100010434).

  2. Author contributions: JJ, VK, LR and VT contributed to the conception and design of the research. LR, ALT, PP and KM performed the experiments. JJ, VK and LR analysed the data. JJ, VK, LR, RGR, SK, LGM and VT interpreted the results of the experiments. JJ drafted the manuscript. JJ, VK, LR, ALT, PP, RGR, SK, KM, LGM and VT edited and revised the manuscript. All authors approved the final version of the manuscript.

  3. Competing interests: None of the authors have a conflict of interest.

  4. Informed consent: Written informed consent was obtained from all individuals included in this study.

  5. Ethical approval: This study was approved by the Medical Ethics Committee of the University of Tartu.

References

1. Daniele, G, Innier, D, Mari, A, Bruder, J, Fourcaudot, M, Pengou, Z, et al.. Sclerostin and insulin resistance in prediabetes: evidence of a cross talk between bone and glucose metabolism. Diabetes Care 2015;38:1509–17. https://doi.org/10.2337/dc14-2989.Search in Google Scholar

2. Neumann, T, Hofbauer, LC, Rauner, M, Lodes, S, Kästner, B, Franke, S, et al.. Clinical and endocrine correlates of circulating sclerostin levels in patients with type 1 diabetes mellitus. Clin Endocrinol 2014;80:649–55. https://doi.org/10.1111/cen.12364.Search in Google Scholar

3. Stanik, J, Kratzsch, J, Landgraf, K, Vogel, M, Thiery, J, Kiess, W, et al.. The bone markers sclerostin, osteoprotegerin, and bone-specific alkaline phosphatase are related to insulin resistance in children and adolescents, independent of their association with growth and obesity. Horm Res Pediatr 2019;91:1–8. https://doi.org/10.1159/000497113.Search in Google Scholar

4. Wedrychowicz, A, Sztefko, K, Starzyk, JB. Sclerostin and its association with insulin resistance in children and adolescents. Bone 2019;120:232–8.10.1016/j.bone.2018.07.021Search in Google Scholar PubMed

5. Wedrychowicz, A, Sztefko, K, Starzyk, JB. Sclerostin and its significance for children and adolescents with type 1 diabetes mellitus. Bone 2019;120:387–92.10.1016/j.bone.2018.08.007Search in Google Scholar PubMed

6. Canalis, E. Wnt signaling in osteoporosis: mechanisms and novel therapeutic approaches. Nat Rev Endocrinol 2013;9:575–83. https://doi.org/10.1038/nrendo.2013.154.Search in Google Scholar

7. Weivoda, MM, Youssef, SJ, Oursler, MJ. Sclerostin expression and functions beyond the osteocyte. Bone 2017;96:45–50. https://doi.org/10.1016/j.bone.2016.11.024.Search in Google Scholar

8. Redlich, K, Smolen, JS. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat Rev Drug Discov 2012;11:234–50. https://doi.org/10.1038/nrd3669.Search in Google Scholar

9. Amrein, K, Amrein, S, Drexler, C, Dimai, HP, Dobnig, H, Pfeifer, K, et al.. Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults. J Clin Endocrinol Metab 2012;97:148–54. https://doi.org/10.1210/jc.2011-2152.Search in Google Scholar

10. Durosier, C, van Lierop, A, Ferrari, S, Chevalley, T, Papapoulos, S, Rizzoli, R. Association of circulating sclerostin with bone mineral mass, microstructure, and turnover biochemical markers in healthy elderly men and women. J Clin Endocrinol Metab 2013;98:3873–83. https://doi.org/10.1210/jc.2013-2113.Search in Google Scholar

11. Garnero, P, Sornay-Rendu, E, Munoz, F, Borel, O, Chapurlat, RD. Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int 2013;24:489–94. https://doi.org/10.1007/s00198-012-1978-x.Search in Google Scholar

12. Moriwaki, K, Matsumoto, H, Tanishima, S, Tanimura, C, Osaki, M, Nagashima, H, et al.. Association of serum bone- and muscle-derived factors with age, sex, body composition, and physical function in community-dwelling middle-aged and elderly adults: a cross-sectional study. BMC Muscoskel Disord 2019;20:276. https://doi.org/10.1186/s12891-019-2650-9.Search in Google Scholar

13. Fischer, DC, Mischek, A, Wolf, S, Rahn, A, Salweski, B, Kundt, G, et al.. Paediatric reference values for the C-terminal fragment of fibroblast growth factor-23, sclerostin, bone-specific alkaline phosphatase and isoform 5b of tartate-resistant acid phosphatase. Ann Clin Biochem 2012;49:546–53. https://doi.org/10.1258/acb.2012.011274.Search in Google Scholar

14. Xu, Y, Gao, C, He, J, Gu, W, Yi, C, Chen, B, et al.. Sclerostin and its associations with bone metabolism markers and sex hormones in healthy community-dwelling elderly individuals and adolescents. Front Cell Dev Biol 2020;8:57. https://doi.org/10.3389/fcell.2020.00057.Search in Google Scholar

15. Kirmani, S, Amin, S, McCready, LK, Atkinson, EJ, Melton, LJ3rd, Müller, R, et al.. Sclerostin levels during growth in children. Osteoporos Int 2012;23:1123–30. https://doi.org/10.1007/s00198-011-1669-z.Search in Google Scholar

16. Janssen, LGM, van Dam, AD, Hanssen, MJW, Kooijman, S, Nahon, KJ, Reinders, H, et al.. Higher plasma sclerostin and lower Wnt signaling gene expression in white adipose tissue of prediabetic South Asian men compared with white Caucasian men. Diabetes Metabol J 2020;44:326–35. https://doi.org/10.4093/dmj.2019.0031.Search in Google Scholar

17. Sheng, Z, Tong, D, Ou, Y, Zhang, H, Zhang, Z, Li, S, et al.. Serum sclerostin levels were positively correlated with fat mass and bone mineral density in central south Chinese postmenopausal women. Clin Endocrinol 2012;76:797–801. https://doi.org/10.1111/j.1365-2265.2011.04315.x.Search in Google Scholar

18. Urano, T, Shiraki, M, Ouchi, Y, Inoue, S. Association of circulating sclerostin levels with fat mass and metabolic disease-related markers in Japanese postmenopausal women. J Clin Endocrinol Metab 2012;97:E1473–7. https://doi.org/10.1210/jc.2012-1218.Search in Google Scholar

19. Jürimäe, J, Tillmann, V, Cicchella, A, Stefanelli, C, Võsoberg, K, Tamm, AL, et al.. Increased sclerostin and preadipocyte factor-1 levels in prepubertal rhythmic gymnasts: associations with bone mineral density, body composition, and adipocytokine values. Osteoporos Int 2016; 27:1239–43. https://doi.org/10.1007/s00198-015-3301-0.Search in Google Scholar

20. Kurgan, N, McKee, K, Calleja, M, Josse, AR, Klentrou, P. Cytokines, adipokines, and bone markers at rest and in response to plyometric exercise in obese vs normal weight adolescent females. Front Endocrinol 2020;11:531926. https://doi.org/10.3389/fendo.2020.531926.Search in Google Scholar

21. Kim, SP, Frey, JL, Li, Z, Kushwaha, P, Zoch, ML, Tomlinson, RE, et al.. Sclerostin influences body composition by regulating catabolic and anabolic metabolism in adipocytes. Proc Natl Acad Sci USA 2017;114:E11238–47. https://doi.org/10.1073/pnas.1707876115.Search in Google Scholar

22. Kim, H, Wrann, CD, Jedrychowski, M, Vidoni, S, Kitase, Y, Nagano, K, et al.. Irisin mediates effects on bone and fat via αV integrin receptors. Cell 2018;175:1756–68. https://doi.org/10.1016/j.cell.2018.10.025.Search in Google Scholar

23. Kirk, B, Feehan, J, Lombardi, G, Duque, G. Muscle, bone, and fat crosstalk: the biological role of myokines, osteokines, and adipokines. Curr Osteoporos Rep 2020;18:388–400. https://doi.org/10.1007/s11914-020-00599-y.Search in Google Scholar

24. Vaiksaar, S, Jürimäe, J, Mäestu, J, Purge, P, Kalytka, S, Shakhlina, L, et al.. No effect of menstrual cycle phase and oral contraceptive use on endurance performance in rowers. J Strength Condit Res 2011;25:1571–8. https://doi.org/10.1519/jsc.0b013e3181df7fd2.Search in Google Scholar

25. De Souza, MJ, West, SL, Jamal, SA, Hawker, GA, Grundberg, CM, Williams, NI. The presence of both an energy deficiency and estrogen deficiency exacerbate alterations of bone metabolism in exercising women. Bone 2008;43:140–8. https://doi.org/10.1016/j.bone.2008.03.013.Search in Google Scholar

26. Jürimäe, J, Cicchella, A, Jürimäe, T, Lätt, E, Haljaste, K, Purge, P, et al.. Regular physical activity influences plasma ghrelin concentration in adolescent girls. Med Sci Sports Exerc 2007;39:1736–41. https://doi.org/10.1249/mss.0b013e31812e5294.Search in Google Scholar

27. Jürimäe, J, Tillmann, V, Purge, P, Jürimäe, T. Body composition, maximal aerobic performance and inflammatory biomarkers in endurance-trained athletes. Clin Physiol Funct Imag 2017;37:288–92. https://doi.org/10.1111/cpf.12299.Search in Google Scholar

28. Kouvelioti, R, Kurgan, N, Falk, B, Ward, WE, Josse, AR, Klentrou, P. Cytokine and sclerostin response to high-intensity interval running versus cycling. Med Sci Sports Exerc 2019;51:2458–64. https://doi.org/10.1249/mss.0000000000002076.Search in Google Scholar

29. Aronis, KN, Kilim, H, Chamberland, JP, Breggia, A, Rosen, C, Mantzoros, CS. Preadipocyte factor-1 levels are higher in women with hypothalamic amenorrhea and are associated with bone mineral content and bone mineral density through a mechanism independent of leptin. J Clin Endocrinol Metab 2011;96:E1634–9. https://doi.org/10.1210/jc.2011-0600.Search in Google Scholar

30. Koehler, K, Williams, NI, Mallinson, RJ, Southmayd, EA, Allaway, HCM, De Souza, MJ. Low resting metabolic rate in exercise-associated amenorrhea is not due to a reduced proportion of highly active metabolic tissue compartments. Am J Physiol Endocrinol Metab 2016;311:E480–7. https://doi.org/10.1152/ajpendo.00110.2016.Search in Google Scholar

31. Grethen, E, Hill, KM, Jones, RM, Cacucci, BM, Gupta, CE, Acton, A, et al.. Serum leptin, parathyroid hormone, 1,25-dihydroxyvitamin D, fibroblast growth factor 23, bone alkaline phosphatase, and sclerostin relationships in obesity. J Clin Endocrinol Metab 2012;97:1655–62. https://doi.org/10.1210/jc.2011-2280.Search in Google Scholar

32. Chen, D, Xie, R, Shu, B, Landay, AL, Wei, C, Reiser, J, et al.. Wnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging. Ann NY Acad Sci 2019;1442:48–60. https://doi.org/10.1111/nyas.13945.Search in Google Scholar

33. Lombardi, G, Lanteri, P, Colombini, A, Mariotti, M, Banfi, G. Sclerostin in athletes: role of load and gender. J Biol Regul Homeost Agents 2012;26:157–63.Search in Google Scholar

34. Kurgan, N, Logan-Sprenger, H, Falk, B, Klentrou, P. Bone and inflammatory responses to training in female rowers over an Olympic year. Med Sci Sports Exerc 2018;50:1810–7. https://doi.org/10.1249/mss.0000000000001640.Search in Google Scholar

35. Grasso, D, Corsetti, R, Lanteri, P, Di Bernardo, C, Colombini, A, Graziani, R, et al.. Bone-muscle unit activity, salivary steroid hormones profile, and physical effort over a 3-week stage race. Scand J Med Sci Sports 2015;25:70–80. https://doi.org/10.1111/sms.12147.Search in Google Scholar

36. Jürimäe, J, Purge, P, Tillmann, V. Serum sclerostin and cytokine responses to prolonged sculling exercise in highly-trained male rowers. J Sports Sci 2021;39:591–7. https://doi.org/10.1080/02640414.2020.1837428.Search in Google Scholar

37. Colaianni, G, Grano, M. Role of irisin on the bone-muscle functional unit. BoneKEy Rep 2015;4:765. https://doi.org/10.1038/bonekey.2015.134.Search in Google Scholar

38. Hew-Butler, T, Landis-Piwowar, K, Byrd, G, Seimer, M, Seigneurie, N, Byrd, B, et al.. Plasma irisin in runners and nonrunners: no favorable metabolic associations in humans. Physiol Rep 2015;3:e12262. https://doi.org/10.14814/phy2.12262.Search in Google Scholar

39. Jürimäe, J, Purge, P. Irisin and inflammatory cytokines in elite male rowers: adaptation to volume-extended training period. J Sports Med Phys Fit 2021;61:102–8.10.23736/S0022-4707.20.11076-4Search in Google Scholar PubMed

40. Maimoun, L, Guillaume, S, Lefebvre, P, Philibert, P, Bertet, H, Picot, MC, et al.. Evidence of a link between resting energy expenditure and bone remodelling, glucose homeostasis and adipokine variations in adolescent girls with anorexia nervosa. Osteoporos Int 2016;27:135–46. https://doi.org/10.1007/s00198-015-3223-x.Search in Google Scholar

41. Singhal, V, Ackerman, KE, Bose, A, Torre Flores, LP, Lee, H, Misra, M. Impact of route of estrogen administration on bone turnover markers in oligoamenorrheic athletes and its mediators. J Clin Endocrinol Metab 2019;104:1449–58. https://doi.org/10.1210/jc.2018-02143.Search in Google Scholar

42. Hamrick, MW. A role of myokines in muscle-bone interactions. Exerc Sport Sci Rev 2011;39:43–7. https://doi.org/10.1097/jes.0b013e318201f601.Search in Google Scholar

43. Jürimäe, J. Interpretation and application of bone turnover markers in children and adolescents. Curr Opin Pediatr 2010;22:494–500. https://doi.org/10.1097/mop.0b013e32833b0b9e.Search in Google Scholar

44. Faje, AT, Fazeli, PK, Katzman, DK, Miller, KK, Breggia, A, Rosen, CJ, et al.. Sclerostin levels and bone turnover markers in adolescents with anorexia nervosa and healthy adolescent girls. Bone 2012;51:474–9. https://doi.org/10.1016/j.bone.2012.06.006.Search in Google Scholar

45. Jürimäe, J, Gruodyte-Raciene, R, Baxter-Jones, ADG. Effects of gymnastics activities on bone accrual during growth: a systematic review. J Sports Sci Med 2018;17:245–58.Search in Google Scholar

46. Tsentidis, C, Gourgiotis, D, Kossiva, L, Marmarinos, A, Doulgeraki, A, Karavanaki, K. Sclerostin distribution in children and adolescents with type 1 diabetes mellitus and correlation with bone metabolism and bone mineral density. Pediatr Diabetes 2016;17:289–99. https://doi.org/10.1111/pedi.12288.Search in Google Scholar

47. Fazeli, PK, Ackerman, KE, Pierce, L, Guereca, G, Bouxsein, M, Misra, M. Sclerostin and Pref-1 have differential effects on bone mineral density and strength parameters in adolescent athletes compared with non-athletes. Osteoporos Int 2013;24:2433–40. https://doi.org/10.1007/s00198-013-2353-2.Search in Google Scholar

48. Kouvelioti, R, LeBlanc, P, Falk, B, Ward, WE, Josse, AR, Klentrou, P. Effects of high-intensity interval running versus cycling on sclerostin, and markers of bone turnover and oxidative stress in young men. Calcif Tissue Int 2019;104:582–90. https://doi.org/10.1007/s00223-019-00524-1.Search in Google Scholar

Received: 2020-11-18
Accepted: 2021-02-12
Published Online: 2021-04-12
Published in Print: 2021-06-25

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