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

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 (+25 pg/mL, p = 0.07) and a significant increase in ghrelin (+ 192 pg/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.