The Skeletal Effects of Short-Term Triple Therapy in a Rat Model of Gastric Ulcer Induced by Helicobacter pylori Infection

Abstract

Purpose

Triple therapy is the standard therapy to eradicate Helicobacter pylori (H.pylori) infection. Chronic use of proton pump inhibitors (PPIs), a component of triple therapy, is associated with osteoporosis. However, the skeletal effects of short-term triple therapy containing PPI remain elusive. This study aims to determine the skeletal effect of short-term triple therapy in a rat model of gastric ulcer induced by H. pylori.

Methods

Three-month-old male Sprague Dawley rats were assigned to normal control, H. pylori-inoculated group (negative control) and H. pylori-inoculated group receiving triple therapy consisting of omeprazole [2.035 mg/kg body weight (b.w)], amoxicillin (102.80 mg/kg b.w) and clarithromycin (51.37 mg/kg b.w) (n=6/group). H. pylori infection developed for four weeks after inoculation, followed by two-week triple therapy. At the end of the treatment period, femoral bones of the rats were harvested for analysis. Bone mineral density and content of the femurs were determined using dual-energy X-ray absorptiometry, while bone strength was measured with a universal mechanical tester.

Results

Bone mineral content was significantly lower in the negative control group compared to the triple therapy group (p=0.014). Triple therapy decreased strain (vs negative control, p=0.002) and displacement of the femur (vs normal control, p=0.004; vs untreated control, p=0.005). No significant difference was observed in other parameters among the study groups (p>0.05).

Conclusion

Short-term triple therapy increases bone mineral content but decreases bone strength of rats. Skeletal prophylaxis should be considered for patients on short-term triple therapy containing PPI.

Keywords:

• bone
• gastric ulcer
• omeprazole
• osteoporosis
• osteopenia
• proton pump inhibitor

Acknowledgments

We would like to thank Mr Mohd Mustazil Mohd Noor, Mr Azlan Mohd Arlamsyah, Ms Juliana Abdul Hamid and Mr Fadhlullah Zuhair Japar Sidik, as well as all laboratory technicians of the Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia for their help and support.

Disclosure

The authors report no conflicts of interest in this work.