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

A.H. Hasanin

Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. helmy_amany@yahoo.com

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• Pharmacology

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.

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