Increases in PYY and uncoupling of bone turnover are associated with loss of bone mass after gastric bypass surgery

doi:10.1016/j.bone.2019.115115

. 2020 Feb:131:115115.

doi: 10.1016/j.bone.2019.115115. Epub 2019 Nov 2.

Increases in PYY and uncoupling of bone turnover are associated with loss of bone mass after gastric bypass surgery

Tiffany Y Kim¹, Dolores M Shoback², Dennis M Black³, Stanley J Rogers⁴, Lygia Stewart⁵, Jonathan T Carter⁴, Andrew M Posselt⁴, Nicole J King², Anne L Schafer⁶

Affiliations

¹ Departments of Medicine, University of California, San Francisco, San Francisco, USA; Endocrine Research Unit, San Francisco VA Health Care System, San Francisco, USA. Electronic address: tiffany.kim@ucsf.edu.
² Departments of Medicine, University of California, San Francisco, San Francisco, USA; Endocrine Research Unit, San Francisco VA Health Care System, San Francisco, USA.
³ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, USA.
⁴ Department of Surgery, University of California, San Francisco, San Francisco, USA.
⁵ Department of Surgery, University of California, San Francisco, San Francisco, USA; Surgical Services, San Francisco VA Health Care System, San Francisco, USA.
⁶ Departments of Medicine, University of California, San Francisco, San Francisco, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, USA; Endocrine Research Unit, San Francisco VA Health Care System, San Francisco, USA.

PMID: 31689523
PMCID: PMC6930344
DOI: 10.1016/j.bone.2019.115115

Increases in PYY and uncoupling of bone turnover are associated with loss of bone mass after gastric bypass surgery

Tiffany Y Kim et al. Bone. 2020 Feb.

. 2020 Feb:131:115115.

doi: 10.1016/j.bone.2019.115115. Epub 2019 Nov 2.

Authors

Tiffany Y Kim¹, Dolores M Shoback², Dennis M Black³, Stanley J Rogers⁴, Lygia Stewart⁵, Jonathan T Carter⁴, Andrew M Posselt⁴, Nicole J King², Anne L Schafer⁶

Affiliations

¹ Departments of Medicine, University of California, San Francisco, San Francisco, USA; Endocrine Research Unit, San Francisco VA Health Care System, San Francisco, USA. Electronic address: tiffany.kim@ucsf.edu.
² Departments of Medicine, University of California, San Francisco, San Francisco, USA; Endocrine Research Unit, San Francisco VA Health Care System, San Francisco, USA.
³ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, USA.
⁴ Department of Surgery, University of California, San Francisco, San Francisco, USA.
⁵ Department of Surgery, University of California, San Francisco, San Francisco, USA; Surgical Services, San Francisco VA Health Care System, San Francisco, USA.
⁶ Departments of Medicine, University of California, San Francisco, San Francisco, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, USA; Endocrine Research Unit, San Francisco VA Health Care System, San Francisco, USA.

PMID: 31689523
PMCID: PMC6930344
DOI: 10.1016/j.bone.2019.115115

Abstract

Context: The gut hormones peptide YY (PYY) and ghrelin mediate in part the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. However, preclinical data suggest these hormones also affect the skeleton and could contribute to postoperative bone loss.

Objective: We investigated whether changes in fasting serum total PYY and ghrelin were associated with bone turnover marker levels and loss of bone mineral density (BMD) after RYGB.

Design, setting, participants: Prospective cohort of adults undergoing RYGB (n=44) at San Francisco academic hospitals.

Main outcome measures: We analyzed 6-month changes in PYY, ghrelin, bone turnover markers, and BMD by dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). We calculated the uncoupling index (UI), reflecting the relative balance of bone resorption and formation.

Results: Postoperatively, there was a trend for an increase in PYY (+25pg/mL, p=0.07) and a significant increase in ghrelin (+192pg/mL, p<0.01). PYY changes negatively correlated with changes in spine BMD by QCT (r=-0.36, p=0.02) and bone formation marker P1NP (r=-0.30, p=0.05). Relationships were significant after adjustments for age, sex, and weight loss. No consistent relationships were found between ghrelin and skeletal outcomes. Mean 6-month UI was -3.3; UI correlated with spine BMD loss by QCT (r=0.40, p=0.01).

Conclusions: Postoperative PYY increases were associated with attenuated increases in P1NP and greater declines in spine BMD by QCT. Uncoupling of bone turnover correlated with BMD loss. These findings suggest a role for PYY in loss of bone mass after RYGB and highlight the relationship between intestinal and skeletal metabolism.

Keywords: BMD; Bone turnover; Ghrelin; PYY; Roux-en-Y gastric bypass surgery.

Published by Elsevier Inc.

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Conflict of interest statement

Competing interests: All authors state that they have no competing interests to declare.

Figures

**Figure 1.**
Six-month change in fasting PYY is negatively correlated with changes in spine volumetric BMD by QCT.

**Figure 2.**
The uncoupling index at 6 months is correlated with change in spine volumetric BMD by QCT.

See this image and copyright information in PMC

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References

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[1] Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004; 292:1724–1737 - PubMed

[2] Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004; 292:1724–1737 - PubMed

[3] Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H, Lystig T, Sullivan M, Bouchard C, Carlsson B, Bengtsson C, Dahlgren S, Gummesson A, Jacobson P, Karlsson J, Lindroos AK, Lonroth H, Naslund I, Olbers T, Stenlof K, Torgerson J, Agren G, Carlsson LM. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007; 357:741–752 - PubMed

[4] Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H, Lystig T, Sullivan M, Bouchard C, Carlsson B, Bengtsson C, Dahlgren S, Gummesson A, Jacobson P, Karlsson J, Lindroos AK, Lonroth H, Naslund I, Olbers T, Stenlof K, Torgerson J, Agren G, Carlsson LM. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007; 357:741–752 - PubMed

[5] Schafer AL, Kazakia GJ, Vittinghoff E, Stewart L, Rogers SJ, Kim TY, Carter JT, Posselt AM, Pasco C, Shoback DM, Black DM. Effects of gastric bypass surgery on bone mass and microarchitecture occur early and particularly impact postmenopausal women. J Bone Miner Res. 2018; 33:975–986 - PMC - PubMed

[6] Schafer AL, Kazakia GJ, Vittinghoff E, Stewart L, Rogers SJ, Kim TY, Carter JT, Posselt AM, Pasco C, Shoback DM, Black DM. Effects of gastric bypass surgery on bone mass and microarchitecture occur early and particularly impact postmenopausal women. J Bone Miner Res. 2018; 33:975–986 - PMC - PubMed

[7] Stein EM, Silverberg SJ. Bone loss after bariatric surgery: causes, consequences, and management. Lancet Diabetes Endocrinol. 2014; 2:165–174 - PMC - PubMed

[8] Stein EM, Silverberg SJ. Bone loss after bariatric surgery: causes, consequences, and management. Lancet Diabetes Endocrinol. 2014; 2:165–174 - PMC - PubMed

[9] Yu EW. Bone metabolism after bariatric surgery. J Bone Miner Res. 2014; 29:1507–1518 - PMC - PubMed

[10] Yu EW. Bone metabolism after bariatric surgery. J Bone Miner Res. 2014; 29:1507–1518 - PMC - PubMed

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Increases in PYY and uncoupling of bone turnover are associated with loss of bone mass after gastric bypass surgery

Affiliations

Increases in PYY and uncoupling of bone turnover are associated with loss of bone mass after gastric bypass surgery

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Conflict of interest statement

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