Promotion effect of extracts from plastrum testudinis on alendronate against glucocorticoid-induced osteoporosis in rat spine

Hui Ren,De Liang,Wenhua Zhao,Jinjing Huang,Xiaobing Jiang,Jingjing Tang,Zhida Zhang,Gengyang Shen,Zhidong Yang,Ting Qiu,Zhensong Yao,Xiang Yu

doi:10.1038/s41598-017-10614-5

Abstract

Alendronate (ALN) is a key therapeutic used to treat glucocorticoid-induced osteoporosis (GIOP), but may induce severe side effects. We showed earlier that plastrum testudinis extracts (PTE) prevented and treated GIOP in vivo. However, clinically, PTE is seldom used alone. Herein, we reveal the synergistic effect of ALN and PTE can treat GIOP of the rat spine and define the mechanism. Sprague-Dawley rats were randomly assigned to four groups: a vehicle group, a GIOP group, an ALN group, and an ALN+PTE group. Each group was further divided into two experimental phases, including dexamethasone (DXM) intervention and withdrawal. Bone mass, microarchitecture, biomechanics, bone-turnover markers, and histomorphology were evaluated. The mRNA and protein expression levels of CTSK and Runx2 were detemined. We found that ALN+PTE improved bone quantity and quality, bone strength, bone turnover; and mitigated histological damage during glucocorticoid intervention and withdrawal. The therapeutic effect was better than that afforded by ALN alone. ALN+PTE reduced CTSK protein expression, promoted Runx2 mRNA and protein expression to varying extents, and more strongly inhibited bone resorption than did ALN alone. Overall, the synergistic effect mediated by ALN+PTE reversed GIOP during DXM intervention and withdrawal via affecting CTSK and Runx2 expression at mRNA and protein levels.

Highlights

Substantial progress has been made in our understanding of the pathogenesis of glucocorticoid-induced osteoporosis (GIOP), the most common form of secondary osteoporosis[1,2,3]
We found no significant difference in any of Bone mineral density (BMD), bone mineral content (BMC), or AREA between ALN and ALN+plastrum testudinis extracts (PTE) groups (Fig. 1A–C)
We explored the synergistic actions of ALN and PTE in vivo, and present a new means treating GIOP

Summary

Introduction

Substantial progress has been made in our understanding of the pathogenesis of glucocorticoid-induced osteoporosis (GIOP), the most common form of secondary osteoporosis[1,2,3]. In the present study, we explore whether PTE acted synergistically with ALN to counter GIOP in terms of bone quality and quantify, expression of bone turnover markers, and bone histology. Previously[13], we confirmed that glucocorticoid (GC) withdrawal for 3 months did not reduce bone impairment in rats with GIOP; we considered that, clinically, continued anti-osteoporosis treatment was required after GC withdrawal. We used a 3-months course of ALN+PTE to treat rats with GIOP after GC withdrawal; we www.nature.com/scientificreports/. To explore the synergistic effect of PTE and ALN on GIOP in detail, rats received oral ALN+PTE both at the time of GC injection and withdrawal. The mRNA and protein expression levels of Cathepsin K (CTSK) and Runx[2] were determined to identify the potential therapeutic targets of ALN+PTE used to treat GIOP

Methods

Results

Conclusion