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Bone resorption following weight loss surgery is associated with treatment procedure and changes in secreted Wnt antagonists

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Abstract

To assess if altered bone turnover following bariatric surgery is related to metabolic consequences of the surgical procedure or weight loss. We evaluated serum markers reflecting bone turnover and metabolic pathways at baseline and after 1-year in a controlled non-randomized clinical trial comparing Roux-en-Y gastric bypass surgery (n = 74) with lifestyle intervention (n = 63) on obesity-related comorbidities. The decrease in body mass index (BMI) was larger in the surgery (−14.0 kg/m2) compared to lifestyle (−3.7 kg/m2). Markedly increased bone turnover was observed following surgery compared to lifestyle intervention and was correlated with change in BMI. Stepwise multivariable regression analysis revealed that group (β = 0.31, p < 0.01), and changes in BMI (β = −0.28, p < 0.01), dickkopf-1 (β = 0.20, p < 0.001) and sclerostin (β = 0.11, p < 0.05) were predictors of change in the bone resorption marker N-terminal telopeptide. Our data support that mechanisms related to the procedure itself and changes in secreted Wnt antagonists may contribute to increased bone turnover following bariatric surgery.

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References

  1. E.W. Yu, Bone metabolism after bariatric surgery. J. Bone Miner. Res. 29, 1507–1518 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  2. M.P. Hage, F.G. El-Hajj, Bone and mineral metabolism in patients undergoing Roux-en-Y gastric bypass. Osteoporos. Int. 25, 423–439 (2014)

    Article  CAS  PubMed  Google Scholar 

  3. E.M. Stein, S.J. Silverberg, Bone loss after bariatric surgery: causes, consequences, and management. Lancet Diab. Endocrinol. 2, 165–174 (2014)

    Article  Google Scholar 

  4. W.J. Pories, Bariatric surgery: risks and rewards. J. Clin. Endocrinol. Metab. 93, S89–S96 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. E.W. Yu, M.L. Bouxsein, M.S. Putman, E.L. Monis, A.E. Roy, J.S. Pratt, W.S. Butsch, J.S. Finkelstein, Two-year changes in bone density after Roux-en-Y gastric bypass surgery. J. Clin. Endocrinol. Metab. 100, 1452–1459 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. A.H. Maghrabi, K. Wolski, B. Abood, A. Licata, C. Pothier, D.L. Bhatt, S. Nissen, S.A. Brethauer, J.P. Kirwan, P.R. Schauer, S.R. Kashyap, Two-year outcomes on bone density and fracture incidence in patients with T2DM randomized to bariatric surgery versus intensive medical therapy. Obesity 23, 2344–2348 (2015)

    Article  PubMed  Google Scholar 

  7. K.M. Nakamura, E.G. Haglind, J.A. Clowes, S.J. Achenbach, E.J. Atkinson, L.J. Melton III, K.A. Kennel, Fracture risk following bariatric surgery: a population-based study. Osteoporos. Int. 25, 151–158 (2014)

    Article  CAS  PubMed  Google Scholar 

  8. A. Lalmohamed, F. de Vries, M.T. Bazelier, A. Cooper, T.P. van Staa, C. Cooper, N.C. Harvey, Risk of fracture after bariatric surgery in the United Kingdom: population based, retrospective cohort study. BMJ 345, e5085 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  9. S. Ahlin, M. Peltonen, L. Anveden, P. Jacobson, K. Sjôholm, P.A. Svensson, I. Larsson, I. Nâslund, L. Sjôstrôm, L.M. Carlsson, Bariatric surgery increases the risk of osteoporosis and fractures in women in the Swedish Obese Subjects study. Obes. Facts 8(Suppl 1), 50–51 (2015)

    Google Scholar 

  10. S. Ikramuddin, C.J. Billington, W.J. Lee, J.P. Bantle, A.J. Thomas, J.E. Connett, D.B. Leslie, W.B. Inabnet III, R.W. Jeffery, K. Chong, L.M. Chuang, M.G. Sarr, M.D. Jensen, A. Vella, L. Ahmed, K. Belani, J.L. Schone, A.E. Olofson, H.A. Bainbridge, P.S. Laqua, Q. Wang, J. Korner, Roux-en-Y gastric bypass for diabetes (the Diabetes Surgery Study): 2-year outcomes of a 5-year, randomised, controlled trial. Lancet Diab. Endocrinol. 3, 413–422 (2015)

    Article  Google Scholar 

  11. M.M. Brzozowska, A. Sainsbury, J.A. Eisman, P.A. Baldock, J.R. Center, Bariatric surgery, bone loss, obesity and possible mechanisms. Obes. Rev. 14, 52–67 (2013)

    Article  CAS  PubMed  Google Scholar 

  12. C. Muschitz, R. Kocijan, C. Marterer, A.R. Nia, G.K. Muschitz, H. Resch, P. Pietschmann, Sclerostin levels and changes in bone metabolism after bariatric surgery. J. Clin. Endocrinol. Metab. 100, 891–901 (2015)

    Article  CAS  PubMed  Google Scholar 

  13. S. Savastano, S.C. Di, L. Barrea, A. Colao, The complex relationship between obesity and the somatropic axis: the long and winding road. Growth Hormon. IGF Res. 24, 221–226 (2014)

    Article  CAS  Google Scholar 

  14. G. Karsenty, F. Oury, The central regulation of bone mass, the first link between bone remodeling and energy metabolism. J. Clin. Endocrinol. Metab. 95, 4795–4801 (2010)

    Article  CAS  PubMed  Google Scholar 

  15. E. Biver, C. Salliot, C. Combescure, L. Gossec, P. Hardouin, I. Legroux-Gerot, B. Cortet, Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 96, 2703–2713 (2011)

    Article  CAS  PubMed  Google Scholar 

  16. D. Hofso, N. Nordstrand, L.K. Johnson, T.I. Karlsen, H. Hager, T. Jenssen, J. Bollerslev, K. Godang, R. Sandbu, J. Roislien, J. Hjelmesaeth, Obesity-related cardiovascular risk factors after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention. Eur. J. Endocrinol. 163, 735–745 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. M. Malone, Recommended nutritional supplements for bariatric surgery patients. Ann. Pharmacother. 42, 1851–1858 (2008)

    Article  CAS  PubMed  Google Scholar 

  18. K. Abegg, N. Gehring, C.A. Wagner, A. Liesegang, M. Schiesser, M. Bueter, T.A. Lutz, Roux-en-Y Gastric bypass surgery reduces bone mineral density and induces metabolic acidosis in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305, R999–R1009 (2013)

    Article  CAS  PubMed  Google Scholar 

  19. A.G. Robling, A.B. Castillo, C.H. Turner, Biomechanical and molecular regulation of bone remodeling. Annu. Rev. Biomed. Eng. 8, 455–498 (2006)

    Article  CAS  PubMed  Google Scholar 

  20. C.S. Riedt, R.E. Brolin, R.M. Sherrell, M.P. Field, S.A. Shapses, True fractional calcium absorption is decreased after Roux-en-Y gastric bypass surgery. Obesity 14, 1940–1948 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. N.A. Sims, T.J. Martin, Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep. 3, 481 (2014)

    PubMed  PubMed Central  Google Scholar 

  22. A.G. Robling, P.J. Niziolek, L.A. Baldridge, K.W. Condon, M.R. Allen, I. Alam, S.M. Mantila, J. Gluhak-Heinrich, T.M. Bellido, S.E. Harris, C.H. Turner, Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J. Biol. Chem. 283, 5866–5875 (2008)

    Article  CAS  PubMed  Google Scholar 

  23. A.R. Wijenayaka, M. Kogawa, H.P. Lim, L.F. Bonewald, D.M. Findlay, G.J. Atkins, Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One 6, e25900 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. K. Fujita, S. Janz, Attenuation of WNT signaling by DKK-1 and -2 regulates BMP2-induced osteoblast differentiation and expression of OPG, RANKL and M-CSF. Mol. Cancer 6, 71 (2007)

    Article  PubMed  PubMed Central  Google Scholar 

  25. Y.W. Qiang, Y. Chen, N. Brown, B. Hu, J. Epstein, B. Barlogie, J.D. Shaughnessy Jr, Characterization of Wnt/beta-catenin signalling in osteoclasts in multiple myeloma. Br. J. Haematol. 148, 726–738 (2010)

    Article  CAS  PubMed  Google Scholar 

  26. L. Pederson, M. Ruan, J.J. Westendorf, S. Khosla, M.J. Oursler, Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc. Natl. Acad. Sci. USA 105, 20764–20769 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. T. Ueland, N.C. Olarescu, A.P. Jorgensen, K. Otterdal, P. Aukrust, K. Godang, T. Lekva, J. Bollerslev, Increased serum and bone matrix levels of the secreted Wnt antagonist DKK-1 in patients with growth hormone deficiency in response to growth hormone treatment. J. Clin. Endocrinol. Metab. 100, 736–743 (2015)

    Article  CAS  PubMed  Google Scholar 

  28. R. Armamento-Villareal, C. Sadler, N. Napoli, K. Shah, S. Chode, D.R. Sinacore, C. Qualls, D.T. Villareal, Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training. J. Bone Miner. Res. 27, 1215–1221 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. A.G. Costa, S. Cremers, E. Dworakowski, M. Lazaretti-Castro, J.P. Bilezikian, Comparison of two commercially available ELISAs for circulating sclerostin. Osteoporos. Int. 25, 1547–1554 (2014)

    Article  CAS  PubMed  Google Scholar 

  30. C. Muschitz, R. Kocijan, J. Haschka, A. Zendeli, T. Pirker, C. Geiger, A. Muller, B. Tschinder, A. Kocijan, C. Marterer, A. Nia, G.K. Muschitz, H. Resch, P. Pietschmann, The impact of vitamin D, calcium, protein supplementation, and physical exercise on bone metabolism after bariatric surgery: the BABS study. J. Bone Miner. Res. (2015). doi:10.1002/jbmr.2707

    Google Scholar 

  31. H.Z. Ke, W.G. Richards, X. Li, M.S. Ominsky, Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr. Rev. 33, 747–783 (2012)

    Article  CAS  PubMed  Google Scholar 

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Morbid Obesity Centre, Department of Medicine, Vestfold Hospital Trust, Tønsberg, Norway

    Dag Hofsø, Rune Sandbu & Jøran Hjelmesæth

  2. Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway

    Dag Hofsø, Jens Bollerslev, Anders Jørgensen & Kristin Godang

  3. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, PO Box 4950, Nydalen, 0424, Oslo, Norway

    Thor Ueland

  4. Faculty of Medicine, University of Oslo, Oslo, Norway

    Jens Bollerslev, Jøran Hjelmesæth & Thor Ueland

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  1. Dag Hofsø
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The regional ethics committee of the Southern Norway Regional Health Authority approved the study. Written informed consent was provided by all participants including permission to perform laboratory analysis.

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Hofsø, D., Bollerslev, J., Sandbu, R. et al. Bone resorption following weight loss surgery is associated with treatment procedure and changes in secreted Wnt antagonists. Endocrine 53, 313–321 (2016). https://doi.org/10.1007/s12020-016-0903-z

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  • DOI: https://doi.org/10.1007/s12020-016-0903-z

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