title: Prediction of bone density around orthopedic implants delivering bisphosphonate.
abstract: The fixation of an orthopedic implant depends strongly upon its initial stability. Peri-implant bone may resorb shortly after the surgery. This resorption is directly followed by new bone formation and implants fixation strengthening, the so-called secondary fixation. If the initial stability is not reached, the resorption continues and the implant fixation weakens, which leads to implant loosening. Studies with rats and dogs have shown that a solution to prevent peri-implant resorption is to deliver bisphosphonate from the implant surface. The aims of the study were, first, to develop a model of bone remodeling around an implant delivering bisphosphonate, second, to predict the bisphosphonate dose that would induce the maximal peri-implant bone density, and third to verify in vivo that peri-implant bone density is maximal with the calculated dose. The model consists of a bone remodeling equation and a drug diffusion equation. The change in bone density is driven by a mechanical stimulus and a drug stimulus. The drug stimulus function and the other numerical parameters were identified from experimental data. The model predicted that a dose of 0.3 microg of zoledronate on the implant would induce a maximal bone density. Implants with 0.3 microg of zoledronate were then implanted in rat femurs for 3, 6 and 9 weeks. We measured that peri-implant bone density was 4% greater with the calculated dose compared to the dose empirically described as best. The approach presented in this paper could be used in the design and analysis processes of experiments in local delivery of drug such as bisphosphonate.
authors.affiliation: Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Stadelmann
authors.forename: Alexandre
authors.initials: A
authors.lastname: Terrier
authors.forename: O
authors.initials: O
authors.lastname: Gauthier
authors.forename: J-M
authors.initials: JM
authors.lastname: Bouler
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Pioletti
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D050071:Bone Density Conservation Agents; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D005269:Femur; D007093:Imidazoles / Q000494:pharmacology*; D008954:Models, Biological; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid