title: The impact of zoledronic acid on regenerate and native bone after consolidation and removal of the external fixator: an animal model study.
abstract: We investigated the role of zoledronic acid on the regenerate and native bone after consolidation and removal of the external fixator in a rabbit model of distraction osteogenesis using 28 New Zealand white rabbits. The rabbits were randomly distributed into two groups. The first group received three doses of zoledronic acid (ZA) 0.1 mg/kg subcutaneously at weekly intervals while the second group received injections of sterile saline. Distraction started on day 7 at a rate of 0.8 mm/day for 12 days. At week 3 the average lengthening, regenerate density, and regenerate continuity were comparable between the two groups. At week 11 the regenerate in the treated group had a significant increase in Bone Mineral Density (BMD) and Bone Mineral Content (BMC) compared to the placebo group. On axial compression, the regenerate showed an increase in the peak load and a higher modulus of elasticity in the treated group. At 6 months, radiographs demonstrated signs of osteopenia of the proximal metaphysis in the control group, and failure of new bone formation around the pin sites in the treated group. BMC and BMD value differences between the two groups were not statistically significant. Histologically, there was persistence of more bone trabeculae in the medullary canal of the regenerate with the persistence of the pin-holes in the treated group. Mechanically, the regenerates in the treated group remain stronger in resisting the axial compression. The proximal fragment in the treated group exhibited a statistically significant decrease in the peak load, toughness and efail %. In conclusion, bisphosphonate-treated rabbits have a stronger regenerate during distraction, and directly after removal of the fixator. They do not develop disuse osteopenia in their lengthened tibia. This treatment may shorten the time in the external fixator and prevent fragility fractures in the treated extremity. However, its long-term safety has not yet been established.
authors.affiliation: Department of Surgery, Division of Orthopedic Surgery, American University of Beirut Medical Center, Beirut, Lebanon. ss15@aub.edu.lb
authors.forename: Said
authors.initials: S
authors.lastname: Saghieh
authors.forename: Nabil J
authors.initials: NJ
authors.lastname: Khoury
authors.forename: Ayman
authors.initials: A
authors.lastname: Tawil
authors.forename: Karim Z
authors.initials: KZ
authors.lastname: Masrouha
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Musallam
authors.forename: Kinda
authors.initials: K
authors.lastname: Khalaf
authors.forename: Laura
authors.initials: L
authors.lastname: Dosh
authors.forename: Rosemarie Reich
authors.initials: RR
authors.lastname: Jaouhari
authors.forename: Ghina
authors.initials: G
authors.lastname: Birjawi
authors.forename: Ghada
authors.initials: G
authors.lastname: El-Hajj-Fuleihan
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D020878:Device Removal; D004164:Diphosphonates / Q000494:pharmacology*; D016267:External Fixators; D007093:Imidazoles / Q000494:pharmacology*; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D011859:Radiography; D013997:Time Factors; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid