title: Does locally delivered Zoledronate influence peri-implant bone formation? - Spatio-temporal monitoring of bone remodeling in vivo.
abstract: Bisphosphonates are known for their strong inhibitory effect on bone resorption. Their influence on bone formation however is less clear. In this study we investigated the spatio-temporal effect of locally delivered Zoledronate on peri-implant bone formation and resorption in an ovariectomized rat femoral model. A cross-linked hyaluronic acid hydrogel was loaded with the drug and applied bilaterally in predrilled holes before inserting polymer screws. Static and dynamic bone parameters were analyzed based on in vivo microCT scans performed first weekly and then biweekly. The results showed that the locally released Zoledronate boosted bone formation rate up to 100% during the first 17 days after implantation and reduced the bone resorption rate up to 1000% later on. This shift in bone remodeling resulted in an increase in bone volume fraction (BV/TV) by 300% close to the screw and 100% further away. The double effect on bone formation and resorption indicates a great potential of Zoledronate-loaded hydrogel for enhancement of peri-implant bone volume which is directly linked to improved implant fixation.
authors.affiliation: Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kettenberger
authors.affiliation: Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Ston
authors.affiliation: Orthopaedic and Traumatology Department, University Hospital Lausanne (CHUV), Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Thein
authors.affiliation: Applied Materials Science, Department of Engineering Sciences, Uppsala University, Sweden.
authors.forename: Philip
authors.initials: P
authors.lastname: Procter
authors.affiliation: Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland. Electronic address: dominique.pioletti@epfl.ch.
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Pioletti
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy* / Q000503:physiopathology; D001863:Bone Screws; D004164:Diphosphonates / Q000008:administration & dosage* / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005260:Female; D005269:Femur / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000077211:Zoledronic Acid
keywords: Bisphosphonate; Drug delivery; Dynamic histomorphometry; Hydrogel; Implant; MicroCT