title: Synergistic local drug delivery in a piglet model of ischemic osteonecrosis: a preliminary study.
abstract: A locally injectable system sequentially delivering an antiresorptive drug (clodronate) followed by an osteogenic agent (simvastatin) was hypothesized to improve femoral head microarchitecture, size, and shape compared with untreated or partial treatment groups in an established piglet osteonecrosis model. After 6 weeks, the clodronate+simvastatin treatment resulted in no collapse, microCT measurements and epiphyseal quotients within 10% of control, normal microstructure, and healthy histology. All other groups exhibited collapse, lower epiphyseal quotients and total femoral head volumes (P<0.05), and abnormal histology. This pilot study provides evidence of synergistic antiresorptive and osteogenic activities, which may prevent femoral head collapse in Perthes disease.
authors.affiliation: Departments of aBiomedical Engineering bOrthopaedic Surgery, University of Kentucky cShriners Hospital for Children, Lexington, Kentucky dDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zou
authors.forename: Paul D
authors.initials: PD
authors.lastname: Fisher
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Horstmann
authors.forename: Vishwas
authors.initials: V
authors.lastname: Talwalkar
authors.forename: Todd A
authors.initials: TA
authors.lastname: Milbrandt
authors.forename: David A
authors.initials: DA
authors.lastname: Puleo
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D004002:Clodronic Acid / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D005270:Femur Head / Q000098:blood supply*; D005271:Femur Head Necrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007511:Ischemia / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D010865:Pilot Projects; D019821:Simvastatin / Q000008:administration & dosage*; D013552:Swine; D013556:Swine, Miniature; D016896:Treatment Outcome; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004002:Clodronic Acid; D019821:Simvastatin