Impact of omeprazole on bone remodeling in normal and ovariectomized Wistar rats.

BACKGROUND Several epidemiologic studies have suggested the association between therapy with proton pump inhibitors (PPIs) and bone fractures. AIM This study aimed at evaluating the effect of omeprazole on bone in normal and ovariectomized Wistar rats and the possible mechanisms involved. MATERIALS AND METHODS 56 rats were divided into 3 main groups. Normal group; further subdivided into normal control group and two groups which were treated with omeprazole in two doses (20, 40 mg/kg/day i.p). Sham operated group. Ovariectomized group; further subdivided into ovariectomized control group, and two groups which were treated with omeprazole in two doses (20, 40 mg/kg/day i.p). Rats were treated for the last 4 weeks of the total 8 weeks of the experiment. Urine hydroxyproline, serum osteocalcin, TNF-α and IL-6 and bone mineral content were assessed. Omeprazole effects on the endothelial dependent and independent relaxation were determined. RESULTS Omeprazole in normal and ovariectomized rats produced significant reduction in bone formation, tibia calcium content and serum TNF-α and IL-6. Omeprazole in ovariectomized rats produced a dose dependent decrease in bone resorption. Isolated aortic rings from ovariectomized/omeprazole treated rats exhibited reversal of the endothelial dysfunction that observed with ovariectomized rats. CONCLUSIONS PPIs might induce both positive and negative effects on bone remodeling. Although these drugs might have the potential to inhibit bone resorption, through suppression of pro-inflammatory cytokines and improvement of endothelial function, yet these effects are counteracted by their inhibitory effects on the gastric proton pump with reduction in calcium absorption and bone formation.