Effect of Systemic Zoledronic Acid Dosing Regimens on Bone Regeneration in Osteoporotic Rats

Marwa Y Shaheen,Hamdan S Alghamdi,Amani M Basudan,Jeroen J J P Van Den Beucken,John A Jansen,Abdurahman A Niazy

doi:10.3390/app11041906

Abstract

The aim of this study was to evaluate the regeneration of bone defects created in the femoral condyle of osteoporotic rats, following intravenous (IV) zoledronate (ZA) treatment in three settings: pre-bone grafting (ZA-Pre), post-bone grafting (ZA-Post), and pre- plus post-bone grafting (ZA-Pre+Post). Twenty-four female Wistar rats were ovariectomized (OVX). After 12 weeks, bone defects were created in the left femoral condyle. All defects were grafted with a particulate inorganic cancellous bovine bone substitute. ZA (0.04 mg/kg, weekly) was administered to six rats 4 weeks pre-bone graft placement. To another six rats, ZA was given post-bone graft placement creation and continued for 6 weeks. Additional six rats received ZA treatment pre- and post-bone graft placement. Control animals received weekly saline intravenous injections. At 6 weeks post-bone graft placement, samples were retrieved for histological evaluation of the bone area percentage (BA%) and remaining bone graft percentage (RBG%). BA% for ZA-Pre (50.1 ± 3.5%) and ZA-Post (49.2 ± 8.2%) rats was significantly increased compared to that of the controls (35.4 ± 5.4%, p-value 0.031 and 0.043, respectively). In contrast, ZA-Pre+Post rats (40.7 ± 16.0%) showed similar BA% compared to saline controls (p = 0.663). For RBG%, all experimental groups showed similar results ranging from 36.3 to 47.1%. Our data indicate that pre- or post-surgical systemic IV administration of ZA improves the regeneration of bone defects grafted with inorganic cancellous bovine-bone particles in osteoporotic bone conditions. However, no favorable effect on bone repair was seen for continued pre- plus post-surgical ZA treatment.

Highlights

Skeletal conditions such as osteoporosis, which further accentuate bone resorption and healing, are a major challenge for bone regenerative processes
All animals were subjected to a bilateral ovariectomy procedure under general anesthesia (GA) to induce osteoporosis, which has been described and reported before [42]
One of the specimens of the ZA Pre+Post group was lost due to problems with the embedding in poly(methyl methacrylate) (pMMA) (Table 1)

Summary

Introduction

Skeletal conditions such as osteoporosis, which further accentuate bone resorption and healing, are a major challenge for bone regenerative processes. The physiological process of bone healing is more complex in situations associated with metabolic disorders compared to healthy condition [1,2]. Osteoporosis decreases both cortical and trabecular bone mineralization and is often diagnosed in postmenopausal women. It is characterized by decreased bone mass and strength, altered bone microstructure, and reduced regenerative capacity [3,4]. The mostly prescribed drugs are bisphosphonates (BPs), which decrease bone turnover by inhibiting osteoclastic cells [5,6] through the disruption of the intracellular processes required for osteoclast function [7]

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