Effects of long-term administration of pantoprazole on bone mineral density in young male rats

Pharmacol Rep. 2016 Oct;68(5):1060-4. doi: 10.1016/j.pharep.2016.06.012. Epub 2016 Aug 20.

Abstract

Background: Epidemiological studies suggest that long-term administration of proton pump inhibitors (PPIs) may decrease bone mineral density (BMD) and increase the risk of osteoporotic fractures. The aim of the study was to assess the influence of pantoprazole on bone metabolism in growing rats.

Methods: The experiment was carried out on twenty-four young male Wistar rats divided into two groups receiving either pantoprazole at the dose of 3mg/kg or vehicle for 12 weeks. Femoral bone mineral density (BMD) and bone histomorphometry were assessed. Serum total calcium, inorganic phosphate and markers of bone turnover were measured.

Results: In pantoprazole-treated rats a decreased BMD was detected (0.2618±0.0133g/cm(2)vs. 0.2715±0.0073g/cm(2), p<0.05). Bone histomorphometry revealed a decrease in growth plate thickness (G.Pl.RTh.) (161.0±27.8μm vs. 195.0±20.8, p<0.05) in pantoprazole-treated animals. Serum total calcium level and osteocalcin concentrations were decreased in the pantoprazole-treated group (9.62±0.55mg/dl vs. 10.15±0.38mg/dl, p<0.05 and 242.7±44.4pg/ml vs. 342.5±123.3pg/ml, p<0.05, respectively).

Conclusion: We observed that PPIs might have a negative impact on bone formation in growing rats mainly due to their inhibitory effects on the gastric proton pump, with probable deterioration of calcium absorption and decrease in growth plate thickness.

Keywords: Bone metabolism; Bone mineral density; Calcium; Pantoprazole; Rats.

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / administration & dosage*
  • Animals
  • Bone Density / drug effects*
  • Bone Diseases, Metabolic / drug therapy
  • Bone Diseases, Metabolic / metabolism
  • Bone Remodeling / drug effects
  • Calcium / metabolism
  • Femur / drug effects*
  • Femur / metabolism
  • Male
  • Osteocalcin / drug effects
  • Ovariectomy / methods
  • Pantoprazole
  • Proton Pump Inhibitors / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Proton Pump Inhibitors
  • Osteocalcin
  • Pantoprazole
  • Calcium