Skeletal effects of nilotinib on prepubertal and pubertal rats

Pharmacy Practice

  • Yasin I. Tayem1Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
  • Wael A. Nasr El-Din2Department of Anatomy, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain., 3Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
  • Aisha N. Rashid2Department of Anatomy, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
  • Sindhan Veeramuthu1Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
  • Manal A. Othman2Department of Anatomy, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain., 4Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Volume 23 Issue 4 Pages 1-8

DOI: 10.18549/PharmPract.2025.4.3320

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.

Keywords

  • Nilotinib
  • Bone
  • Calcification
  • Puberty
Pharmacy Practice

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