Changes in cortical bone channels network and osteocyte organization after the use of zoledronic acid.

Gustavo Davi Rabelo,Marina Gallottini,Marcelo Emílio Beletti,Marcio Augusto Oliveira,Bruno Augusto Nassif Travençolo,Fernando Ricardo Xavier Da Silveira

doi:10.1590/2359-3997000000097

Abstract

The aim of this study was to evaluate the effects of zoledronic acid (ZA) on the cortical bone channels network (CBCN) and osteocyte organization in relation to the bone channels. Eighteen male Wistar rats were divided into control (CG) and test groups (TG). Twelve animals from TG received 3 ZA doses (7.5 µg/kg), and 6 animals from CG did not receive any medication. TG animals were euthanized at 14 (n = 6) and 75 (n = 6) dadys after drug injection. CBCN was analyzed in mandibles and tibias using computational routines. The osteocyte organization was qualitatively evaluated in tibias using a three-dimensional reconstruction of images from serial histological sections. Significant differences in CBCN of tibia were found between the treated and untreated rats, with a wider range of sizes and shapes of the channels after the use of ZA (channels area p = 0.0063, channels area SD p = 0.0276) and less bone matrix (bone volume p = 0.0388). The alterations in the channels' morphology were more evident at 75 days after the drug injection (channels perimeter p = 0.0286). No differences were found in mandibles CBCN. The osteocyte distribution revealed more variable patterns of cell distribution in ZA groups, with non-homogeneous distribution of cells in relation to the bone channels. Zoledronic acid induces structural changes in CBCN and modifies the osteocyte arrangement in cortical bone in the tibia; also, the variability in the morphology of bone channels became more evident after a certain time of the use of the drug.

Highlights

Bisphosphonates (BP) have become the standard class of drugs for treating patients with osteoporosis and in preventing and treating skeletal complications in patients with cancer [1]
The histological analysis in all animals revealed the presence of cortical bone with Haversian channels and osteocytes, with the bone channels network revealing specific characteristics in the different types of bone
After administration of zoledronic acid (ZA), the bone channels structure changed the topography of the network, revealing channels with higher values of OI area and OI area standard deviation in both test groups (TG) subgroups (ZA14D and ZA75D) (Table 1)

Summary

Introduction

Bisphosphonates (BP) have become the standard class of drugs for treating patients with osteoporosis and in preventing and treating skeletal complications in patients with cancer [1]. Intravenous (IV) zoledronic acid (ZA), a commonly used BP, has been classified as a heterocyclic nitrogen-containing bisphosphonate that potently inhibits osteoclastic bone resorption in various short-term in vitro and in vivo pharmacological screening models [2]. Several studies have assessed the effects of ZA on bone properties, including biochemical characteristics, remodeling rates, structural changes, and biomechanical features. Studies evaluating cortical bone characteristics revealed dose- and timing-dependent effects on turnover, microstructure, and mechanical properties [4,5,6,7]. Concerning microarchitecture, it is known that bone multicellular units are changed, and together with an anti-angiogenic effect, the zoledronic acid could cause a decrease (or complete loss of) of intraosseous vascularity [1]

Methods

Results

Conclusion