title: Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study.
abstract: It is a clinical challenge to obtain a sufficient orthopaedic implant fixation in weak osteoporotic bone. When the primary implant fixation is poor, micromotions occur at the bone-implant interface, activating osteoclasts, which leads to implant loosening. Bisphosphonate can be used to prevent the osteoclastic response, but when administered systemically its bioavailability is low and the time it takes for the drug to reach the periprosthetic bone may be a limiting factor. Recent data has shown that delivering bisphosphonate locally from the implant surface could be an interesting solution. Local bisphosphonate delivery increased periprosthetic bone density, which leads to a stronger implant fixation, as demonstrated in rats by the increased implant pullout force. The aim of the present study was to verify the positive effect on periprosthetic bone remodelling of local bisphosphonate delivery in an osteoporotic sheep model. Four implants coated with zoledronate and two control implants were inserted in the femoral condyle of ovariectomized sheep for 4 weeks. The bone at the implant surface was 50% higher in the zoledronate-group compared to control group. This effect was significant up to a distance of 400mum from the implant surface. The presented results are similar to what was observed in the osteoporotic rat model, which suggest that the concept of releasing zoledronate locally from the implant to increase the implant fixation is not species specific. The results of this trial study support the claim that local zoledronate could increase the fixation of an implant in weak bone.
authors.affiliation: Laboratory of Biomechanical Orthopedics EPFL-DAL, IBI, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
authors.forename: V A
authors.initials: VA
authors.lastname: Stadelmann
authors.forename: O
authors.initials: O
authors.lastname: Gauthier
authors.forename: A
authors.initials: A
authors.lastname: Terrier
authors.forename: J M
authors.initials: JM
authors.lastname: Bouler
authors.forename: D P
authors.initials: DP
authors.lastname: Pioletti
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D020007:Implants, Experimental; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D010865:Pilot Projects; D012756:Sheep; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid