title: Local delivery of recombinant human bone morphogenetic proteins and bisphosphonate via sucrose acetate isobutyrate can prevent femoral head collapse in Legg-Calve-Perthes disease: a pilot study in pigs.
abstract: OBJECTIVE
  Legg-Calve-Perthes disease is a paediatric condition encompassing idiopathic osteonecrosis of the femoral head (ONFH). Preventing collapse and the need for subsequent joint replacement remains the major goal of clinical management. This exploratory study utilises a porcine model of surgically induced ONFH.
  
  
  METHODS
  rhBMP-2 with and without zoledronic acid (ZA) was delivered by intra-osseous injection in the phase-transitioning sucrose acetate isobutyrate (SAIB) in an attempt to prevent femoral head collapse. Epiphyseal quotient (EQ) at eight weeks post-surgery was the primary outcome measure. Heterotopic ossification in the joint capsule and bisphosphonate retention in the femoral head were key secondary outcomes.
  
  
  RESULTS
  Femoral heads with ONFH and no treatment all collapsed (3/3, EQ < 0.4, P < 0.05 compared to no ONFH). Local delivery of rhBMP-2/SAIB into the femoral head prevented collapse by EQ measurement one of four samples; however, this specimen still showed evidence of significant collapse. In contrast, the combination of local rhBMP-2 and local ZA prevented collapse in two of four samples. Confocal fluorescence microscopy showed locally dosed bisphosphonate entered and was retained in the femoral head. This group also showed strong Calcein signal, indicating new bone formation. Treatment with rhBMP-2 was associated with a limited amount of heterotrophic ossification in the joint capsules in some specimens.
  
  
  CONCLUSIONS
  Operators reported SAIB to be an efficient way to deliver rhBMP-2 to the femoral head. These data suggest that rhBMP-2 is ineffective for preventing femoral head collapse without the addition of bisphosphonate. Further research will be required to validate the clinical efficacy of a combined local rhBMP-2/bisphosphonate approach.
authors.affiliation: Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Research Building, Locked Bag 4001, Westmead, Sydney, NSW, 2145, Australia.
authors.forename: Tegan L
authors.initials: TL
authors.lastname: Cheng
authors.forename: Ciara M
authors.initials: CM
authors.lastname: Murphy
authors.forename: Laurence C
authors.initials: LC
authors.lastname: Cantrill
authors.forename: Kathy
authors.initials: K
authors.lastname: Mikulec
authors.forename: Clare
authors.initials: C
authors.lastname: Carpenter
authors.forename: Aaron
authors.initials: A
authors.lastname: Schindeler
authors.forename: David G
authors.initials: DG
authors.lastname: Little
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage*; D004337:Drug Carriers; D005271:Femur Head Necrosis / Q000209:etiology / Q000517:prevention & control*; D007093:Imidazoles / Q000008:administration & dosage*; D007267:Injections; D007873:Legg-Calve-Perthes Disease / Q000150:complications / Q000188:drug therapy*; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000008:administration & dosage; D013395:Sucrose / Q000031:analogs & derivatives; D013552:Swine; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D013395:Sucrose; D000077211:Zoledronic Acid; C002885:sucrose acetate isobutyrate