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.