Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Bariatric Surgery

The curious fate of bone following bariatric surgery: bone effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in mice

Abstract

Background

Bone loss and increased fracture risk following bariatric surgery has been reported. We investigated whether the two most commonly performed surgeries, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), lead to bone loss. In addition, we examined whether fortification of the diet with calcium citrate prevents bone loss.

Methods

We used mouse models for SG and RYGB and compared bone loss with a group of sham mice with similar weight loss. All groups were switched at the time of surgery to a low-fat diet (LFD). We also examined whether fortification of the diet with calcium citrate and vitamin D was able to prevent bone loss.

Results

At 2 weeks we observed no major bone effects. However, at 8 weeks, both trabecular and cortical bone were lost to the same extent after SG and RYGB, despite increased calcium absorption and adequate serum levels of calcium, vitamin D, and parathyroid hormone (PTH). Diet fortification with calcium citrate and vitamin D was able to partially prevent bone loss.

Conclusions

Both SG and RYGB lead to excess bone loss, despite intestinal adaptations to increase calcium absorption. Fortifying the diet with calcium citrate and vitamin D partly prevented the observed bone loss. This finding emphasizes the importance of nutritional support strategies after bariatric surgery, but also affirms that the exact mechanisms leading to bone loss after bariatric surgery remain elusive and thus warrant further research.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: BW, activity, and bone parameters after sham, SG, and RYGB.
Fig. 2: Serum PTH, food intake, calcium intake, intestinal absorption, and gene expression analysis 2 and 8 weeks after surgery.
Fig. 3: Renal calcium excretion and gene expression analysis 2 and 8 weeks after surgery.
Fig. 4: Bone parameters after sham, SG, and RYGB with calcium citrate and vitamin D supplementation.
Fig. 5: Intestinal absorption and gene expression analysis 8 weeks after surgery on calcium citrate and vitamin D fortified diets.
Fig. 6: Renal calcium excretion and gene expression analysis 8 weeks after surgery on calcium and vitamin D fortified diets.
Fig. 7: Overview of changes in bones, intestines, and kidneys after SG and RYGB.

Similar content being viewed by others

References

  1. World Health Organization. Obesity and overweight factsheet. Accessed 25 July 2019. http://www.who.int/mediacentre/factsheets/fs311/en/.

  2. Rousseau C, Jean S, Gamache P, Lebel S, Mac-Way F, Biertho L, et al. Change in fracture risk and fracture pattern after bariatric surgery: nested case-control study. BMJ. 2016;354:i3794.

    Article  Google Scholar 

  3. Blom-Høgestøl IK, Hewitt S, Chahal-Kummen M, Brunborg C, Gulseth HL, Kristinsson JA, et al. Bone metabolism, bone mineral density and low-energy fractures 10 years after Roux-en-Y gastric bypass. Bone. 2019;127:436–45.

    Article  Google Scholar 

  4. Zhang Q, Chen Y, Li J, Chen D, Cheng Z, Xu S, et al. A meta-analysis of the effects of bariatric surgery on fracture risk. Obes Rev. 2018;19:728–36.

    Article  CAS  Google Scholar 

  5. Schafer AL, Kazakia GJ, Vittinghoff E, Stewart L, Rogers SJ, Kim TY, et al. Effects of gastric bypass surgery on bone mass and microarchitecture occur early and particularly impact postmenopausal women. J Bone Miner Res. 2018;33:975–86.

    Article  Google Scholar 

  6. Yu EW, Lee MP, Landon JE, Lindeman KG, Kim SC. Fracture risk after bariatric surgery: Roux-en-Y gastric bypass versus adjustable gastric banding. J Bone Miner Res. 2017;32:1229–36.

    Article  Google Scholar 

  7. Corbeels K, Verlinden L, Lannoo M, Simoens C, Matthys C, Verstuyf A, et al. Thin bones: vitamin D and calcium handling after bariatric surgery. Bone Rep. 2018;8:57–63.

    Article  Google Scholar 

  8. Maghrabi AH, Wolski K, Abood B, Licata A, Pothier C, Bhatt DL, et al. Two-year outcomes on bone density and fracture incidence in patients with T2DM randomized to bariatric surgery versus intensive medical therapy. Obesity. 2015;23:2344–8.

    Article  Google Scholar 

  9. Carrasco F, Basfi-Fer K, Rojas P, Valencia A, Csendes A, Codoceo J, et al. Changes in bone mineral density after sleeve gastrectomy or gastric bypass: relationships with variations in vitamin D, ghrelin, and adiponectin levels. Obes Surg. 2014;24:877–84.

    Article  Google Scholar 

  10. Vilarrasa N, de Gordejuela AG, Gómez-Vaquero C, Pujol J, Elio I, San José P, et al. Effect of bariatric surgery on bone mineral density: comparison of gastric bypass and sleeve gastrectomy. Obes Surg. 2013;23:2086–91.

    Article  Google Scholar 

  11. Muschitz C, Kocijan R, Haschka J, Zendeli A, Pirker T, Geiger C, et al. The impact of vitamin D, calcium, protein supplementation, and physical exercise on bone metabolism after bariatric surgery: the BABS study. J Bone Miner Res. 2016;31:672–82.

    Article  CAS  Google Scholar 

  12. Hsin MC, Huang CK, Tai CM, Yeh LR, Kuo HC, Garg A. A case-matched study of the differences in bone mineral density 1 year after 3 different bariatric procedures. Surg Obes Relat Dis. 2015;11:181–5.

    Article  Google Scholar 

  13. Muschitz C, Kocijan R, Marterer C, Nia AR, Muschitz GK, Resch H, et al. Sclerostin levels and changes in bone metabolism after bariatric surgery. J Clin Endocrinol Metab. 2015;100:891–901.

    Article  CAS  Google Scholar 

  14. Pluskiewicz W, Bužga M, Holéczy P, Bortlík L, Šmajstrla V, Adamczyk P. Bone mineral changes in spine and proximal femur in individual obese women after laparoscopic sleeve gastrectomy: a short-term study. Obes Surg. 2012;22:1068–76.

    Article  Google Scholar 

  15. Adamczyk P, Bužga M, Holéczy P, Švagera Z, Zonča P, Sievänen H, et al. Body size, bone mineral density, and body composition in obese women after laparoscopic sleeve gastrectomy: a 1-year longitudinal study. Horm Metab Res. 2015;47:873–9.

    Article  CAS  Google Scholar 

  16. Li Z, Hardij J, Evers SS, Hutch CR, Choi SM, Shao Y, et al. G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche. J Clin Investig. 2019;130:2404–16.

    Article  Google Scholar 

  17. Shanbhogue VV, Støving RK, Frederiksen KH, Hanson S, Brixen K, Gram J, et al. Bone structural changes after gastric bypass surgery evaluated by HR-pQCT: a two-year longitudinal study. Eur J Endocrinol. 2017;176:685–93.

    Article  CAS  Google Scholar 

  18. Yu EW, Bouxsein ML, Putman MS, Monis EL, Roy AE, Pratt JS, et al. Two-year changes in bone density after Roux-en-Y gastric bypass surgery. J Clin Endocrinol Metab. 2015;100:1452–9.

    Article  CAS  Google Scholar 

  19. Bredella MA, Greenblatt LB, Eajazi A, Torriani M, Yu EW. Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on bone mineral density and marrow adipose tissue. Bone. 2017;95:85–90.

    Article  Google Scholar 

  20. von Mach MA, Stoeckli R, Bilz S, Kraenzlin M, Langer I, Keller U. Changes in bone mineral content after surgical treatment of morbid obesity. Metabolism. 2004;53:918–21.

    Article  Google Scholar 

  21. Parrott J, Frank L, Rabena R, Craggs-Dino L, Isom KA, Greiman L. American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the surgical weight loss patient 2016 update: micronutrients. Surg Obes Relat Dis. 2017;13:727–41.

    Article  Google Scholar 

  22. Busetto L, Dicker D, Azran C, Batterham RL, Farpour-Lambert N, Fried M, et al. Practical recommendations of the obesity management task force of the European Association for the Study of Obesity for the post-bariatric surgery medical management. Obes Facts. 2017;10:597–632.

    Article  Google Scholar 

  23. Seyfried F, Lannoo M, Gsell W, Tremoleda JL, Bueter M, Olbers T, et al. Roux-en-Y gastric bypass in mice–surgical technique and characterisation. Obesity surgery. 2012;22:1117–25.

    Article  CAS  Google Scholar 

  24. Sherf Dagan S, Goldenshluger A, Globus I, Schweiger C, Kessler Y, Kowen Sandbank G, et al. Nutritional recommendations for adult bariatric surgery patients: clinical practice. Adv Nutr. 2017;8:382–94.

    Article  Google Scholar 

  25. Lutz TA, Bueter M. The use of rat and mouse models in bariatric surgery experiments. Front Nutr. 2016;3:25.

    Article  Google Scholar 

  26. Dubois V, Laurent MR, Jardi F, Antonio L, Lemaire K, Goyvaerts L, et al. Androgen deficiency exacerbates high-fat diet-induced metabolic alterations in male mice. Endocrinology. 2016;157:648–65.

    Article  CAS  Google Scholar 

  27. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010;25:1468–86.

    Article  Google Scholar 

  28. Daci E, Verstuyf A, Moermans K, Bouillon R, Carmeliet G. Mice lacking the plasminogen activator inhibitor 1 are protected from trabecular bone loss induced by estrogen deficiency. J Bone Miner Res. 2000;15:1510–6.

    Article  CAS  Google Scholar 

  29. Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, et al. Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 2013;28:2–17.

    Article  Google Scholar 

  30. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.

    Article  CAS  Google Scholar 

  31. Sinnesael M, Laurent MR, Jardi F, Dubois V, Deboel L, Delisser P, et al. Androgens inhibit the osteogenic response to mechanical loading in adult male mice. Endocrinology. 2015;156:1343–53.

    Article  CAS  Google Scholar 

  32. Harris LA, Kayser BD, Cefalo C, Marini L, Watrous JD, Ding J. et al. Biliopancreatic diversion induces greater metabolic improvement than Roux-en-Y gastric bypass. Cell Metab. 2019;30:855–64.e3.

    Article  CAS  Google Scholar 

  33. Cavin JB, Couvelard A, Lebtahi R, Ducroc R, Arapis K, Voitellier E. et al. Differences in alimentary glucose absorption and intestinal disposal of blood glucose after Roux-en-Y gastric bypass vs sleeve gastrectomy. Gastroenterology. 2016;150:454–64.e9.

    Article  CAS  Google Scholar 

  34. Nguyen NQ, Debreceni TL, Bambrick JE, Chia B, Deane AM, Wittert G, et al. Upregulation of intestinal glucose transporters after Roux-en-Y gastric bypass to prevent carbohydrate malabsorption. Obesity. 2014;22:2164–71.

    Article  CAS  Google Scholar 

  35. Kellett GL. Alternative perspective on intestinal calcium absorption: proposed complementary actions of Ca(v)1.3 and TRPV6. Nutr Rev. 2011;69:347–70.

    Article  Google Scholar 

  36. Hood MM, Corsica J, Bradley L, Wilson R, Chirinos DA, Vivo A. Managing severe obesity: understanding and improving treatment adherence in bariatric surgery. J Behav Med. 2016;39:1092–103.

    Article  Google Scholar 

  37. Galioto R, Gunstad J, Heinberg LJ, Spitznagel MB. Adherence and weight loss outcomes in bariatric surgery: does cognitive function play a role? Obes Surg. 2013;23:1703–10.

    Article  Google Scholar 

  38. Gacs G, Barltrop D. Significance of Ca-soap formation for calcium absorption in the rat. Gut. 1977;18:64–8.

    Article  CAS  Google Scholar 

  39. Corwin RL, Hartman TJ, Maczuga SA, Graubard BI. Dietary saturated fat intake is inversely associated with bone density in humans: analysis of NHANES III. J Nutr. 2006;136:159–65.

    Article  CAS  Google Scholar 

  40. Kwon YM, Kim GW, Yim HW, Paek YJ, Lee KS. Association between dietary fat intake and bone mineral density in Korean adults: data from Korea National Health and Nutrition Examination Survey IV (2008–2009). Osteoporos Int. 2015;26:969–76.

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank K. Moermans and R. Van Looveren for their histological preparation of bone samples and G. Molenberghs from the Interuniversity Institute for Biostatistics and Statistical Bioinformatics for his assistance with statistical analyses. This work was supported by the FWO (Flemish Research Council) grant numbers 1S27317N and 1802714N. The authors do not have any conflicts of interest to disclose.

Funding

This work was supported by the FWO (Flemish Research Council) [grant numbers 1S27317N and 1802714 N]. Bart Van der Schueren is a clinical researcher of FWO (Flemish Research Council).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katrien Corbeels.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Corbeels, K., Verlinden, L., Lannoo, M. et al. The curious fate of bone following bariatric surgery: bone effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in mice. Int J Obes 44, 2165–2176 (2020). https://doi.org/10.1038/s41366-020-0626-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-020-0626-3

This article is cited by

Search

Quick links