A Proton Pump Inhibitor's Effect on Bone Metabolism Mediated by Osteoclast Action in Old Age: A Prospective Randomized Study

Gut Liver. 2015 Sep 23;9(5):607-14. doi: 10.5009/gnl14135.


Background/aims: Proton pump inhibitors (PPIs) act by irreversibly binding to the H(+)-K(+)-ATPase of the proton pump in parietal cells and may possibly affect the vacuolar H(+)-ATPase in osteoclasts.

Methods: We investigated the effect of 8 weeks of PPI treatment on the parameters of bone turnover and compared PPI with revaprazan, which acts by reversibly binding to H(+)-K(+)-ATPase in proton pumps. This study was a parallel randomized controlled trial. For 8 weeks, either a PPI or revaprazan was randomly assigned to patients with gastric ulcers. The parameters of bone turnover were measured at the beginning of and after the 8-week treatment period.

Results: Twenty-six patients (PPI, n=13; revaprazan, n=13) completed the intention-to-treat analysis. After the 8-week treatment period, serum calcium and urine deoxypyridinoline (DPD) were increased in the PPI group (serum calcium, p=0.046; urine DPD, p=0.046) but not in the revaprazan group. According to multivariate linear regression analysis, age ≥60 years was an independent predictor for the changes in serum calcium and urine DPD.

Conclusions: In elderly patients, administering a PPI for 8 weeks altered bone parameters. Our study suggested that PPIs might directly alter bone metabolism via the vacuolar H(+)-ATPase in osteoclasts.

Keywords: Bone metabolism; Hydrogen potassium ATPase; Osteoclasts; Osteoporosis; Proton pump inhibitors.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acids / drug effects
  • Amino Acids / urine
  • Bone Remodeling / drug effects*
  • Bone and Bones / metabolism*
  • Calcium / blood
  • Female
  • Humans
  • Intention to Treat Analysis
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Osteoclasts / metabolism*
  • Prospective Studies
  • Proton Pump Inhibitors / pharmacology*
  • Pyrimidinones / pharmacology*
  • Tetrahydroisoquinolines / pharmacology*


  • Amino Acids
  • Proton Pump Inhibitors
  • Pyrimidinones
  • Tetrahydroisoquinolines
  • YH 1885
  • deoxypyridinoline
  • Calcium