Short-term effects of zoledronate on the histomorphology of osteoclast in young albino rats

Abstract

The present study was conducted to histomorphometrically evaluate the effects of short-term administration of zoledronate, a third generation bisphosphonate, on the metaphysis of the proximal end of tibia in twenty day old male albino rats. Zoledronate (2.8 μg/kg body weight), was daily given subcutaneously for eleven days. The animals were sacrificed; tibiae were dissected out and decalcified in EDTA. Seven micron thick, serial longitudinal paraffin sections were stained with haematoxylin and eosin and examined under a Zeiss light microscope and Image Pro-Express Analyzer. In zoledronate treated rats, a significant increase (p<0.05) in the number of osteoclasts was observed both in the regions of primary spongiosa (zoledronate treated: 6.41 ± 0.30/mm(2), control: 2.90 ± 0.28/mm(2)) and secondary spongiosa (zoledronate treated: 49.58 ± 0.84/mm(2), control: 31.81 ± 2.02/mm(2)) along with a significant increase (p<0.05) in the length of the metaphyseal region as compared to the control group. The number of nuclei per osteoclast and area of the osteoclast also showed a significant increase (p<0.001; p<0.05 respectively) following the uptake of zoledronate. The findings in the present study, suggest that the osteoclasts are the primary sites of action of zoledronate resulting in decreased osteoclastic activity, which would account for the great increase in the number and size of inactive osteoclasts resulting in marked cancellous bone formation.