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

IntroductionEpidemiological 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.MethodsThe experiment was carried out on twenty-four young male Wistar rats divided into two groups receiving either pantoprazole at the dose of 3 mg/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.ResultsIn pantoprazole-treated rats a decreased BMD was detected (0.2618 ± 0.0133 g/cm2vs. 0.2715 ± 0.0073 g/cm2, p < 0.05). Bone histomorphometry revealed a decrease in growth plate thickness (G.Pl.RTh.) (161.0 ± 27.8 μm 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 ± 0.55 mg/dl vs. 10.15 ± 0.38 mg/dl, p < 0.05 and 242.7 ± 44.4 pg/ml vs. 342.5 ± 123.3 pg/ml, p < 0.05, respectively).ConclusionWe 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.