A Histological Study on the Short-Term Effects of Zoledronate, A Third Generation Bisphosphonate, on the Trabeculae of Growing Bone of Tibia in Albino Rats

Document Type : Original Article

Authors

1 North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), India

2 Former Professor (retired currently) Department of Anatomy, University College of Medical Sciences (UCMS), Delhi - 110095, India.

3 Former Head of Department & Professor (retired currently) Department of Anatomy, University College of Medical Sciences (UCMS), Delhi - 110095, India.

Abstract

Introduction: Zoledronate, a third generation bisphosphonate, is a potent bisphosphonate in inhibiting excessive osteoclastic mediated bone resorption. Bisphosphonates show strong affinity to hydroxyapatite crystals in mineralized bone matrix, where they get incorporated by osteoclast, the primary target cell and inhibit osteoclastic bone resorption through multiple complex mechanisms, and increase the trabecular bone mass. As not many histological studies on the short-term effects of zoledronate on growing bone are available, hence this study was undertaken.
Materials and Methods: Twenty days old male albino rats (n=15) were randomly divided into two groups. Control group I (eight animals) were given equal volume of normal saline according to body weight. The experimental group II (seven animals) were given 2.8μg/kg body weight of zoledronate subcutaneous, daily for eleven days. All animals were sacrificed on thirty-first day. Tibiae were dissected out, decalcified in ethylene diamine tetra acetic acid and processed for paraffin sectioning. Seven μm thick sections were stained with hematoxylin and eosin and Masson’s trichrome stains. The slides were examined under Zeiss light microscope and the findings were analyzed with Image Pro-Express Analyzer.
Results: We observed a significant increase (p < 0.001) in the number of trabeculae both in the regions of primary spongiosa (zoledronate treated: 14.69±1.14/mm2) and secondary spongiosa (zoledronate treated: 11.96±0.29/mm2) in the experimental treated group. The mean width and mean area of trabeculae were seen to be statistically significant (p < 0.001) in the zoledronate treated group as compared to control saline treated group.
Conclusion: The present study showed a significant increased trabecular bone mass in the metaphyseal region following short-term administration of zoledronate despite presence of numerous large polymorphic osteoclasts, the bone resorbing cells. Short-term administration of zoledronate could be highly beneficial in pediatric metabolic bone disorders such as osteoporosis, osteogenesis imperfecta and fibrous dysplasia.

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