Local application of ibandronate/gelatin sponge improves osteotomy healing in rabbits.

Zongyou Yang,Yueju Liu,Bin Xu,Chi Zhang,Tao Geng,James T Triffitt,Zhaoxu Yang,Yingze Zhang,Shaun Peggrem,Han Li,Zhidao Xia,Wei Chen,James Cray

doi:10.1371/journal.pone.0125807

Abstract

Delayed healing or non-union of skeletal fractures are common clinical complications. Ibandronate is a highly potent anti-catabolic reagent used for treatment of osteopenia and fracture prevention. We hypothesized that local application of ibandronate after fracture fixation may improve and sustain callus formation and therefore prevent delayed healing or non-union. This study tested the effect of local application of an ibandronate/gelatin sponge composite on osteotomy healing. A right-side distal-femoral osteotomy was created surgically, with fixation using a k-wire, in forty adult male rabbits. The animals were divided into four groups of ten animals and treated by: (i) intravenous injection of normal saline (Control); (ii) local implantation of absorbable gelatin sponge (GS); (iii) local implantation of absorbable GS containing ibandronate (IB+GS), and (iv) intravenous injection of ibandronate (IB i.v.). At two and four weeks the affected femora were harvested for X-ray photography, computed tomography (CT), biomechanical testing and histopathology. At both time-points the results showed that the calluses in both the ibandronate-treated groups, but especially in the IB+GS group, were significantly larger than in the control and GS groups. At four weeks the cross sectional area (CSA) and mechanical test results of ultimate load and energy in the IB+GS group were significantly higher than in other groups. Histological procedures showed a significant reduction in osteoclast numbers in the IB+GS and IB i.v. groups at day 14. The results indicate that local application of an ibandronate/gelatin sponge biomaterial improved early osteotomy healing after surgical fixation and suggest that such treatment may be a valuable local therapy to enhance fracture repair and potentially prevent delayed or non-union.

Highlights

Fracture non-union is a common clinical complication which can affect 5–10% of surgicallytreated fractures [1]
No significant differences in body weight were found among the groups and animals resumed normal activity within two days after surgery
At 2 and 4 weeks post operation, as seen in Table 1, the cross sectional area (CSA), measured from the computed tomography (CT) scan, in the IB group was significantly higher than that in the Control and gelatin sponge (GS) groups; the CSA in the IB+GS group was significantly higher than those seen in all other groups

Summary

Introduction

Fracture non-union is a common clinical complication which can affect 5–10% of surgicallytreated fractures [1]. Non-union after fracture is difficult to heal without intervention. Current therapies for non-union comprise either non-surgical or surgical treatments. Surgical treatments for non-union involve the use of autografts, allografts or synthetic bone substitute biomaterials, with or without anabolic reagents such as bone morphogenetic proteins (BMPs) [2]. Patients who have suffered multiple fractures, extensive periosteal stripping, soft tissue damage, segment loss, infection or soft tissue necrosis are at high risk of non-union [3,4,5,6,7]. There is no available strategy which has the potential to prevent non-union in high-risk patients

Methods

Results

Discussion

Conclusion