Supplement With Calcium or Alendronate Suppresses Osteopenia Due to Long Term Rabeprazole Treatment in Female Mice: Influence on Bone TRAP and Osteopontin Levels

Aly A M Shaalan; Mohamed El-Sherbiny; Taghrid B El-Abaseri; Mohamed Z Shoaeir; Tarek M Abdel-Aziz; Magda I Mohamed; Sawsan A Zaitone; Hala M F Mohammad

doi:10.3389/fphar.2020.00583

Supplement With Calcium or Alendronate Suppresses Osteopenia Due to Long Term Rabeprazole Treatment in Female Mice: Influence on Bone TRAP and Osteopontin Levels

Front Pharmacol. 2020 May 13:11:583. doi: 10.3389/fphar.2020.00583. eCollection 2020.

Authors

Aly A M Shaalan^{1

2}, Mohamed El-Sherbiny^{3

4}, Taghrid B El-Abaseri⁵, Mohamed Z Shoaeir⁶, Tarek M Abdel-Aziz⁶, Magda I Mohamed⁷, Sawsan A Zaitone^{8

9}, Hala M F Mohammad^{10

11}

Affiliations

¹ Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
² Department of Anatomy, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia.
³ Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁴ Department of Anatomy, College of Medicine, Almaarefa University, Riyadh, Saudi Arabia.
⁵ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
⁶ Department of Rheumatology and Rehabilitation, Al-Azhar Asyut Faculty of Medicine for Men, Asyut, Egypt.
⁷ Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
⁸ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
⁹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
¹⁰ Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
¹¹ Central Laboratory, Center of Excellence in Molecular and Cellular Medicine (CEMCM), Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Abstract

Background and purpose: Rabeprazole, a proton pump inhibitor (PPIs) is much endorsed to patients with increased gastric acidity. PPIs were accused to have osteoporotic effects on patients who chronically use them. The point of the current investigation was to decide the impact of rabeprazole on osteoporosis and to explore the modulatory effects of dietary calcium or alendronate on this side effect.

Methods: 80 female mice were alienated into four groups maintained for 18 weeks: [1] Vehicle group: given distilled water in 12 ml/kg, P.O. [2] Rabeprazole control group: given rabeprazole in a dose equals 10 mg/kg every 48 h, P.O. [3] Rabeprazole + calcium: given rabeprazole (10 mg/kg every 48 h) along with calcium supplement. [4] Rabeprazole + alendronate: given rabeprazole (10 mg/kg every 48 h) and alendronate (1 mg/kg per week, i.p.). Serum calcium, phosphorus and parathyroid hormone were measured. Both femurs were kept in paraformaldehyde, and then the right one was used for X-ray examination with analysis by Digora software and the left one for histopathological examination (H&E) and immunohistochemical stains for osteopontin and tartrate resistant acid phosphatase (TRAP).

Results: Calcium supplementation or administration of alendronate along with rabeprazole significantly restored the mean bone density as shown by X-ray analysis. Femurs from mice received rabeprazole showed widely separated, thin-walled bone trabeculae and increased number of osteoclasts. Calcium or alendronate with rabeprazole showed thick bone trabeculae without full recovery from rabeprazole induced damage. Adding calcium supplementation to rabeprazole did not affect the histological abnormalities related to osteoclasts meanwhile alendronate produced inactivation of osteoclasts. Both calcium and alendronate decreased the rabeprazole-induced increment in the femur osteopontin level.

Conclusion: Calcium or alendronate can be recommended for female patients on PPI therapy who are at risk of osteopenia.

Keywords: alendronate; calcium; osteopenia; osteopontin; rabeprazole; tartrate resistant acid phosphatase.