Zoledronic Acid Prevents Disuse Osteopenia And Augments Gene Expression Of Osteoclastic Differentiation Markers In Mice

Objectives: Disuse is characterized by a rapid and profound bone resorption. Zoledronic acid (Zol) inhibits osteoclastic bone resorption. The aim of the study was to prevent disuse osteopenia with Zol and investigate gene expression markers of osteoclastic differentiation. Methods: Disuse osteopenia was induced by injecting botulinum toxin (BTX) into the right hind limb of 16-week-old C57BL/6J female mice. Zol (100 mu g/kg) was injected s. c. once at study start. The immobilized bones were investigated with DEXA, microCT, mechanical testing, dynamic bone histomorphometry, and RT-qPCR. Results: The BTX-injections resulted in a loss of cortical and trabecular bone as well as mechanical strength compared to intact baseline and control mice. Treatment with Zol prevented the loss of bone and mechanical strength. Interestingly, treatment with Zol resulted in a higher expression of Nfatc1 and Dcstamp, which are markers osteoclastic differentiation. Conclusions: Zol effectively prevented BTX-induced disuse osteopenia. Furthermore, gene expression markers of osteoclastic differentiation were increased in Zol treated immobilized mice, indicating that Zol only affect mature bone resorbing osteoclasts in vivo. However, the current findings are preliminary and calls for further studies.