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. 2020 Dec 3:14:5359-5366.
doi: 10.2147/DDDT.S287239. eCollection 2020.

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

Affiliations

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

Sophia Ogechi Ekeuku et al. Drug Des Devel Ther. .

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; osteopenia; osteoporosis; proton pump inhibitor.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Comparison of the body weight between groups across the study period.
Figure 2
Figure 2
Photomicrographs of the gastric mucosa of the rats. The haematoxylin and eosin stained micrographs of the negative control group show gastric mucosa lesion (red arrow), while the gastric mucosa is intact for the normal control and triple therapy group. The Giemsa stained micrographs of the negative control group show spiral bacilli in the mucosa layer (black arrows).
Figure 3
Figure 3
Femoral weight (A), length (B), area (C) and (D) diameter of the rats in different groups.
Figure 4
Figure 4
Bone mineral density (A) and bone mineral content (B) of the ex-vivo samples.
Figure 5
Figure 5
Bone mechanical strength indices of the rats investigated using the three-point-bending test, which derives force (A), strain (B), stress (C), Young’s modulus (D), displacement (E), stiffness (F).

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Grants and funding

We would like to acknowledge the Ministry of Higher Education Malaysia (FRGS/1/2016/SKK08/UKM/02/5) and Universiti Kebangsaan Malaysia (FF-2018-422) for financial support. Dr Sophia Ogechi Ekeuku is a postdoctoral researcher funded by Universiti Kebangsaan Malaysia through FPR-1.