Skeletal effects of nilotinib on prepubertal and pubertal rats

Main Article Content

Yasin I. Tayem
MD, PhD, Professor of Pharmacology and Therapeutics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Arabian Gulf University, Manama

Wael A. Nasr El-Din
MD, PhD, Associate Professor of Anatomy, Department of Anatomy, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain, and Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia

Aisha N. Rashid
MSC in Genetics, Technician, Department of Anatomy, College of Medicine and Health Sciences, Arabian Gulf University, Manama

Sindhan Veeramuthu
MSc in Pharmacy, Technician, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Arabian Gulf University, Manama

Manal A. Othman
MD, PhD, Associate Professor of Anatomy, Department of Anatomy, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain. Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut

Keywords

Nilotinib, Bone, Calcification, Puberty

Abstract

Background: Nilotinib belongs to a group of anti-cancer drugs called tyrosine kinase inhibitors (TKIs), which are currently the mainstay treatment of chronic myeloid leukemia (CML). Objectives: In this study, we aimed to investigate the effects of this drug on bones around puberty in vivo. Methods: Juvenile male Wistar rats were divided to three groups and were treated orally once a day. Group 1 was administered vehicle; group 2 was administered nilotinib at a low-dose (30.85 mg/kg) and group 3 was treated with a high-dose (41.13 mg/kg). The treatment continued from week 4 until week 7 of age (pre-pubertal and pubertal life). Methods: Serum calcium, insulin-like growth factor-1 (IGF-1) and procollagen type I (PINP) were measured by enzyme-linked immunosorbent assay (ELISA). Femur bone was collected for histopathological evaluation using Hematoxylin & Eosin stain, and Masson's trichrome (MTC) staining. Immunohistochemistry was performed, using the bone cellular markers antiosteopontin (OPN) and antitartrate-resistant acid phosphatase (TRAP). Results: Serum Calcium, IGF-1 and PINP declined in a dose-dependent manner (p < 0.05). Histopathological evaluation revealed dose-dependent degeneration of bone lamellae and disruption and disorganization of cellular components. Moreover, the study revealed a decrease in collagen, decrease in OPN, and increase in TRAP immunostaining. Conclusion: Nilotinib had deleterious skeletal effects around puberty, possibly requiring long-term monitoring of bone growth and mineralization.

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Jan 9, 2026

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Skeletal effects of nilotinib on prepubertal and pubertal rats. Pharm Pract (Granada) [Internet]. 2026 Jan. 9 [cited 2026 Jan. 22];23(4):1-8. Available from: https://pharmacypractice.org/index.php/pp/article/view/3320
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Vol. 23 No. 4 (2025): Oct-Dec
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Original Research
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1.
Skeletal effects of nilotinib on prepubertal and pubertal rats. Pharm Pract (Granada) [Internet]. 2026 Jan. 9 [cited 2026 Jan. 22];23(4):1-8. Available from: https://pharmacypractice.org/index.php/pp/article/view/3320