title: Local delivery of bisphosphonate from coated orthopedic implants increases implants mechanical stability in osteoporotic rats.
abstract: Patients with osteoporosis and joint disabilities represent a constant growing and challenging population to be treated in the musculoskeletal clinical field. Especially in the case of total hip arthroplasty, new solutions should be developed to compensate for the double negative factors, peri-implant osteolysis, and osteoporotic bone loss, affecting the quality of implant outcome. The goal of this study was then to establish a proof of concept for orthopedic implant used as Zoledronate delivery in osteoporotic rats, and in particular, to verify if this approach could increase the initial implant stability. Twenty-five female 6-month-old Wistar rats were ovariectomized 6 weeks before the implantation to induce osteoporosis. The animals were randomly separated in five groups representing the different Zoledronate concentrations in the HA coating: 0, 0.2, 2.1, 8.5, and 16 microg/implant. Histomorphometric measures and peri-implant bone volume fraction were assessed and mechanical stability tests were performed. Bone volume fraction and biomechanical results clearly illustrate the positive effect of Zoledronate coated implants in the osteoporotic rats. A remarkable result was to show the existence of a window of Zoledronate content (0.2 to 8.5 microg/implant) in which the mechanical fixation of the implant increased. We were able to establish the proof of concept for orthopedic implants used as a drug delivery system in osteoporotic rats. The local bisphosphonate delivery from a calcium phosphate coating allowed increase of the mechanical fixation of an orthopedic implant. This study shows that orthopedic implants containing bisphosphonates could be beneficial for osteoporotic patients in need of a total joint replacement.
authors.affiliation: Bone Bioengineering Group, Laboratory of Orthopedic Research, Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland.
authors.forename: Bastian
authors.initials: B
authors.lastname: Peter
authors.forename: Olivier
authors.initials: O
authors.lastname: Gauthier
authors.forename: Samia
authors.initials: S
authors.lastname: Laïb
authors.forename: Bruno
authors.initials: B
authors.lastname: Bujoli
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guicheux
authors.forename: Pascal
authors.initials: P
authors.lastname: Janvier
authors.forename: G Harry
authors.initials: GH
authors.lastname: van Lenthe
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Zambelli
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bouler
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Pioletti
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery*; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D000077211:Zoledronic Acid
chemical_list: D020099:Coated Materials, Biocompatible; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid