title: Local application of ibandronate/gelatin sponge improves osteotomy healing in rabbits.
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.
authors.affiliation: Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050051 P R China; Key Laboratory of Orthopaedic Biomechanics of Hebei Province, Shijiazhuang, 050051, P R China; Orthopaedic Research Institution of Hebei Province, Hebei, P R China.
authors.forename: Zongyou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050051 P R China; Key Laboratory of Orthopaedic Biomechanics of Hebei Province, Shijiazhuang, 050051, P R China; Orthopaedic Research Institution of Hebei Province, Hebei, P R China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, SA2 8PP, United Kingdom.
authors.forename: Zhidao
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050051 P R China; Key Laboratory of Orthopaedic Biomechanics of Hebei Province, Shijiazhuang, 050051, P R China; Orthopaedic Research Institution of Hebei Province, Hebei, P R China.
authors.forename: Yueju
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, SA2 8PP, United Kingdom.
authors.forename: Shaun
authors.initials: S
authors.lastname: Peggrem
authors.affiliation: Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050051 P R China; Key Laboratory of Orthopaedic Biomechanics of Hebei Province, Shijiazhuang, 050051, P R China; Orthopaedic Research Institution of Hebei Province, Hebei, P R China.
authors.forename: Tao
authors.initials: T
authors.lastname: Geng
authors.affiliation: Department of Orthopaedic Surgery, Hebei General Hospital, Shijiazhuang, 050051, P.R. China.
authors.forename: Zhaoxu
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050051 P R China; Key Laboratory of Orthopaedic Biomechanics of Hebei Province, Shijiazhuang, 050051, P R China; Orthopaedic Research Institution of Hebei Province, Hebei, P R China.
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050051 P R China; Key Laboratory of Orthopaedic Biomechanics of Hebei Province, Shijiazhuang, 050051, P R China; Orthopaedic Research Institution of Hebei Province, Hebei, P R China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050051 P R China; Key Laboratory of Orthopaedic Biomechanics of Hebei Province, Shijiazhuang, 050051, P R China; Orthopaedic Research Institution of Hebei Province, Hebei, P R China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Botnar Research Centre, Nuffield Orthopaedic Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom OX37LD.
authors.forename: James T
authors.initials: JT
authors.lastname: Triffitt
authors.affiliation: Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050051 P R China; Key Laboratory of Orthopaedic Biomechanics of Hebei Province, Shijiazhuang, 050051, P R China; Orthopaedic Research Institution of Hebei Province, Hebei, P R China.
authors.forename: Yingze
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004164:Diphosphonates / Q000008:administration & dosage*; D005780:Gelatin / Q000008:administration & dosage*; D000077557:Ibandronic Acid; D008297:Male; D010027:Osteotomy; D011817:Rabbits; D014945:Wound Healing
chemical_list: D004164:Diphosphonates; D005780:Gelatin; D000077557:Ibandronic Acid