Display options
Cite
Abildgaard J, Johansen MY, Skov-Jeppesen K, et al. Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial. Med Sci Sports Exerc. 2022;54(1):38-46doi: 10.1249/MSS.0000000000002776.
Abildgaard, J., Johansen, M. Y., Skov-Jeppesen, K., Andersen, L. B., Karstoft, K., Hansen, K. B., Hartmann, B., Holst, J. J., Pedersen, B. K., & Ried-Larsen, M. (2022). Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial. Medicine and science in sports and exercise, 54(1), 38-46. https://doi.org/10.1249/MSS.0000000000002776
Abildgaard, Julie, et al. "Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial." Medicine and science in sports and exercise vol. 54,1 (2022): 38-46. doi: https://doi.org/10.1249/MSS.0000000000002776
Abildgaard J, Johansen MY, Skov-Jeppesen K, Andersen LB, Karstoft K, Hansen KB, Hartmann B, Holst JJ, Pedersen BK, Ried-Larsen M. Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial. Med Sci Sports Exerc. 2022 Jan 01;54(1):38-46. doi: 10.1249/MSS.0000000000002776. PMID: 34431828.
Copy Download .nbib Format: NLM
Share it on

Med Sci Sports Exerc. 2022 Jan 01;54(1):38-46. doi: 10.1249/MSS.0000000000002776.

Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial.

Medicine and science in sports and exercise

Julie Abildgaard, Mette Yun Johansen, Kirsa Skov-Jeppesen, Lars Bo Andersen, Kristian Karstoft, Katrine Bagge Hansen, Bolette Hartmann, Jens Juul Holst, Bente Klarlund Pedersen, Mathias Ried-Larsen

Affiliations

  1. The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, DENMARK.
  2. Department of Sport, Food and Natural Sciences, Faculty of Education, Arts and Sports, Western Norway University of Applied Sciences, Campus Sogndal, Sogndal, NORWAY.
  3. Steno Diabetes Center Copenhagen, Gentofte, DENMARK.

PMID: 34431828 DOI: 10.1249/MSS.0000000000002776

Abstract

INTRODUCTION/PURPOSE: The increased risk of fractures with type 2 diabetes (T2D) is suggested to be caused by decreased bone turnover. Current international guidelines recommend lifestyle modifications, including exercise, as first-line treatment for T2D. The aim of this study was to investigate the effects of an exercise-based lifestyle intervention on bone turnover and bone mineral density (BMD) in persons with T2D.

METHODS: Persons with T2D were randomized to either a 12-month lifestyle intervention (n = 64) or standard care (n = 34). The lifestyle intervention included five to six weekly aerobic training sessions, half of them combined with resistance training. Serum markers of bone turnover (osteocalcin, N-terminal propeptide of type-I procollagen, reflecting bone formation, and carboxyterminal collagen I crosslinks, reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up.

RESULTS: From baseline to follow-up, s-propeptide of type-I procollagen increased by 34% (95% confidence interval [CI], 17%-50%), serum-carboxyterminal collagen I crosslink by 36% (95% CI, 1%-71%), and s-osteocalcin by 31% (95% CI, 11-51%) more in the lifestyle intervention group compared with standard care. Loss of weight and fat mass were the strongest mediators of the increased bone turnover. Bone mineral density was unaffected by the intervention (ΔBMD, 0.1%; 95% CI, -1.1% to 1.2%).

CONCLUSIONS: A 12-month intensive exercise-based lifestyle intervention led to a substantial but balanced increase in bone turnover in persons with T2D. The increased bone turnover combined with a preserved BMD, despite a considerable weight loss, is likely to reflect improved bone health and warrants further studies addressing the impact of exercise on risk of fractures in persons with T2D.

Copyright © 2021 by the American College of Sports Medicine.

References

  1. Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007;166(5):495–505. - PubMed
  2. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int. 2007;18(4):427–44. - PubMed
  3. Oei L, Zillikens MC, Dehghan A, et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: the Rotterdam Study. Diabetes Care. 2013;36(6):1619–28. - PubMed
  4. de Abreu LLF, Holloway-Kew KL, Sajjad MA, Kotowicz MA, Pasco JA. FRAX (Australia) scores in women with impaired fasting glucose and diabetes. Bone Rep. 2019;11:100223. - PubMed
  5. Poiana C, Capatina C. Fracture risk assessment in patients with diabetes mellitus. J Clin Densitom. 2017;20(3):432–43. - PubMed
  6. Kanazawa I, Tanaka KI, Takeo A, et al. A scoring assessment tool for the risk of vertebral fractures in patients with type 2 diabetes mellitus. Bone. 2019;122:38–44. - PubMed
  7. Napoli N, Chandran M, Pierroz DD, et al. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. 2017;13(4):208–19. - PubMed
  8. Krakauer JC, McKenna MJ, Buderer NF, et al. Bone loss and bone turnover in diabetes. Diabetes. 1995;44(7):775–82. - PubMed
  9. Manavalan JS, Cremers S, Dempster DW, et al. Circulating osteogenic precursor cells in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012;97(9):3240–50. - PubMed
  10. Purnamasari D, Puspitasari MD, Setiyohadi B, Nugroho P, Isbagio H. Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study. BMC Endocr Disord. 2017;17(1):72. - PubMed
  11. Hygum K, Starup-Linde J, Harslof T, Vestergaard P, Langdahl BL. Mechanisms in endocrinology: diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis. Eur J Endocrinol. 2017;176(3):R137–57. - PubMed
  12. Kanazawa I, Yamaguchi T, Yamamoto M, et al. Serum osteocalcin/bone-specific alkaline phosphatase ratio is a predictor for the presence of vertebral fractures in men with type 2 diabetes. Calcif Tissue Int. 2009;85(3):228–34. - PubMed
  13. Jiajue R, Jiang Y, Wang O, et al. Suppressed bone turnover was associated with increased osteoporotic fracture risks in non-obese postmenopausal Chinese women with type 2 diabetes mellitus. Osteoporos Int. 2014;25(8):1999–2005. - PubMed
  14. Starup-Linde J, Hygum K, Langdahl BL. Skeletal fragility in type 2 diabetes mellitus. Endocrinol Metab (Seoul). 2018;33(3):339–51. - PubMed
  15. Stage TB, Christensen MH, Jorgensen NR, et al. Effects of metformin, rosiglitazone and insulin on bone metabolism in patients with type 2 diabetes. Bone. 2018;112:35–41. - PubMed
  16. Wang L, Li T, Liu J, et al. Association between glycosylated hemoglobin A1c and bone biochemical markers in type 2 diabetic postmenopausal women: a cross-sectional study. BMC Endocr Disord. 2019;19(1):31. - PubMed
  17. Tonks KT, White CP, Center JR, Samocha-Bonet D, Greenfield JR. Bone turnover is suppressed in insulin resistance, independent of adiposity. J Clin Endocrinol Metab. 2017;102(4):1112–21. - PubMed
  18. Balint E, Szabo P, Marshall CF, Sprague SM. Glucose-induced inhibition of in vitro bone mineralization. Bone. 2001;28(1):21–8. - PubMed
  19. Oshima K, Nampei A, Matsuda M, et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun. 2005;331(2):520–6. - PubMed
  20. Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100(2):197–207. - PubMed
  21. Eleftheriadis T, Kartsios C, Antoniadi G, et al. The impact of chronic inflammation on bone turnover in hemodialysis patients. Ren Fail. 2008;30(4):431–7. - PubMed
  22. Koh JM, Khang YH, Jung CH, et al. Higher circulating hsCRP levels are associated with lower bone mineral density in healthy pre- and postmenopausal women: evidence for a link between systemic inflammation and osteoporosis. Osteoporos Int. 2005;16(10):1263–71. - PubMed
  23. Kong YY, Feige U, Sarosi I, et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999;402(6759):304–9. - PubMed
  24. Carstensen M, Herder C, Kivimaki M, et al. Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes. 2010;59(5):1222–7. - PubMed
  25. Khosla S, Peterson JM, Egan K, Jones JD, Riggs BL. Circulating cytokine levels in osteoporotic and normal women. J Clin Endocrinol Metab. 1994;79(3):707–11. - PubMed
  26. Langdahl BL, Lokke E, Carstens M, Stenkjaer LL, Eriksen EF. Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1-receptor antagonist gene but not with polymorphisms in the interleukin-1beta gene. J Bone Miner Res. 2000;15(3):402–14. - PubMed
  27. Villareal DT, Chode S, Parimi N, et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med. 2011;364(13):1218–29. - PubMed
  28. Shah K, Armamento-Villareal R, Parimi N, et al. Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones. J Bone Miner Res. 2011;26(12):2851–9. - PubMed
  29. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of diabetes. Diabetes Care. 2015;38(1):140–9. - PubMed
  30. Skoradal MB, Weihe P, Patursson P, et al. Football training improves metabolic and cardiovascular health status in 55- to 70-year-old women and men with prediabetes. Scand J Med Sci Sports. 2018;28(1 Suppl):42–51. - PubMed
  31. Johansen MY, Karstoft K, MacDonald CS, et al. Effects of an intensive lifestyle intervention on the underlying mechanisms of improved glycaemic control in individuals with type 2 diabetes: a secondary analysis of a randomised clinical trial. Diabetologia. 2020;63(11):2410–22. - PubMed
  32. Johansen MY, MacDonald CS, Hansen KB, et al. Effect of an Intensive lifestyle intervention on glycemic control in patients with type 2 diabetes: a randomized clinical trial. JAMA. 2017;318(7):637–46. - PubMed
  33. Ried-Larsen M, Christensen R, Hansen KB, et al. Head-to-head comparison of intensive lifestyle intervention (U-TURN) versus conventional multifactorial care in patients with type 2 diabetes: protocol and rationale for an assessor-blinded, parallel group and randomised trial. BMJ Open. 2015;5(12):e009764. - PubMed
  34. MacDonald CS, Johansen MY, Nielsen SM, et al. Dose-response effects of exercise on glucose-lowering medications for type 2 diabetes: a secondary analysis of a randomized clinical trial. Mayo Clin Proc. 2020;95(3):488–503. - PubMed
  35. Ried-Larsen M, MacDonald CS, Johansen MY, et al. Why prescribe exercise as therapy in type 2 diabetes? We have a pill for that! Diabetes Metab Res Rev. 2018;34(5):e2999. - PubMed
  36. Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. BMJ. 1990;300(6719):230–5. - PubMed
  37. Baron RM, Kenny DA. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol. 1986;51(6):1173–82. - PubMed
  38. Wold SRA, Wold H, Dunn WJ. The collinearity problem in linear regression the partial least squares (PLS) approach to generalized inverses. SIAM J Sci Stat Comput. 1984;5(3):735–43. - PubMed
  39. Chen X, Zhang J, Zhou Z. Changes in bone mineral density after weight loss due to metabolic surgery or lifestyle intervention in obese patients. Obes Surg. 2021;31(3):1147–57. - PubMed
  40. Komorita Y, Iwase M, Fujii H, et al. Impact of body weight loss from maximum weight on fragility bone fractures in Japanese patients with type 2 diabetes: the Fukuoka Diabetes Registry. Diabetes Care. 2018;41(5):1061–7. - PubMed
  41. Hinton PS, Nigh P, Thyfault J. Effectiveness of resistance training or jumping-exercise to increase bone mineral density in men with low bone mass: a 12-month randomized, clinical trial. Bone. 2015;79:203–12. - PubMed
  42. Shao X, Cao X, Song G, Zhao Y, Shi B. Metformin rescues the MG63 osteoblasts against the effect of high glucose on proliferation. J Diabetes Res. 2014;2014:453940. - PubMed
  43. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8–27. - PubMed
  44. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98–107. - PubMed
  45. Kitazawa R, Kimble RB, Vannice JL, Kung VT, Pacifici R. Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice. J Clin Invest. 1994;94(6):2397–406. - PubMed
  46. Lee YM, Fujikado N, Manaka H, Yasuda H, Iwakura Y. IL-1 plays an important role in the bone metabolism under physiological conditions. Int Immunol. 2010;22(10):805–16. - PubMed
  47. Maagensen H, Junker AE, Jorgensen NR, et al. Bone turnover markers in patients with nonalcoholic fatty liver disease and/or type 2 diabetes during oral glucose and isoglycemic intravenous glucose. J Clin Endocrinol Metab. 2018;103(5):2042–9. - PubMed
  48. Lopes LS, Schwartz RP, Ferraz-de-Souza B, et al. The role of enteric hormone GLP-2 in the response of bone markers to a mixed meal in postmenopausal women with type 2 diabetes mellitus. Diabetol Metab Syndr. 2015;7:13. - PubMed
  49. Hygum K, Harslof T, Jorgensen NR, et al. Bone resorption is unchanged by liraglutide in type 2 diabetes patients: a randomised controlled trial. Bone. 2020;132:115197. - PubMed
  50. Iepsen EW, Lundgren JR, Hartmann B, et al. GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women. J Clin Endocrinol Metab. 2015;100(8):2909–17. - PubMed
  51. Driessen JH, de Vries F, van Onzenoort H, et al. The use of incretins and fractures - a meta-analysis on population-based real life data. Br J Clin Pharmacol. 2017;83(4):923–6. - PubMed
  52. Zhang YS, Weng WY, Xie BC, et al. Glucagon-like peptide-1 receptor agonists and fracture risk: a network meta-analysis of randomized clinical trials. Osteoporos Int. 2018;29(12):2639–44. - PubMed
  53. Tian A, Ma J, Feng K, et al. Reference markers of bone turnover for prediction of fracture: a meta-analysis. J Orthop Surg Res. 2019;14(1):68. - PubMed
  54. Jorde R, Stunes AK, Kubiak J, et al. Effects of vitamin D supplementation on bone turnover markers and other bone-related substances in subjects with vitamin D deficiency. Bone. 2019;124:7–13. - PubMed
  55. Lombardi G, Ziemann E, Banfi G, Corbetta S. Physical activity-dependent regulation of parathyroid hormone and calcium-phosphorous metabolism. Int J Mol Sci. 2020;21(15):5388. - PubMed

Publication Types