title: Local administration of bone morphogenetic protein-2 and bisphosphonate during non-weight-bearing treatment of ischemic osteonecrosis of the femoral head: an experimental investigation in immature pigs.
abstract: BACKGROUND
  Non-weight-bearing decreases the femoral head deformity but increases bone resorption without increasing bone formation in an experimental animal model of Legg-Calvé-Perthes disease. We sought to determine if local administration of bone morphogenetic protein (BMP)-2 with or without bisphosphonate can increase the bone formation during the non-weight-bearing treatment in the large animal model of Legg-Calvé-Perthes disease.
  
  
  METHODS
  Eighteen piglets were surgically induced with femoral head ischemia. Immediately following the surgery, all animals received an above-the-knee amputation to enforce local non-weight-bearing (NWB). One to two weeks later, six animals received local BMP-2 to the necrotic head (BMP group), six received local BMP-2 and ibandronate (BMP+IB group), and the remaining six received no treatment (NWB group). All animals were killed at eight weeks after the induction of ischemia. Radiographic, microcomputed tomography (micro-CT), and histomorphometric assessments were performed.
  
  
  RESULTS
  Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP+IB groups had a decrease of 20%, 14%, and 10%, respectively, in their mean epiphyseal quotient in comparison with the normal control group. Micro-CT analyses showed significantly higher femoral head bone volume in the BMP+IB group than in the BMP group (p = 0.02) and the NWB group (p < 0.001). BMP+IB and BMP groups had a significantly higher trabecular number (p < 0.01) and lower trabecular separation (p < 0.02) than the NWB group. In addition, the osteoclast number per bone surface was significantly lower in the BMP+IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP+IB groups than in the NWB group (p < 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP+IB group but not in the BMP group.
  
  
  CONCLUSIONS
  Administration of BMP-2 with bisphosphonate best decreased bone resorption and increased new bone formation during non-weight-bearing treatment of ischemic osteonecrosis in a pig model, but heterotopic ossification is a concern.
  
  
  CONCLUSIONS
  This preclinical study provides new evidence that BMP-2 with bisphosphonate can effectively prevent the extreme bone loss associated with the non-weight-bearing treatment and increase new bone formation in the femoral head in this animal model of ischemic osteonecrosis.
authors.affiliation: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX 75219. E-mail address for H.K.W. Kim: harry.kim@tsrh.org.
authors.forename: Harry K W
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX 75219. E-mail address for H.K.W. Kim: harry.kim@tsrh.org.
authors.forename: Olumide
authors.initials: O
authors.lastname: Aruwajoye
authors.affiliation: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX 75219. E-mail address for H.K.W. Kim: harry.kim@tsrh.org.
authors.forename: Justin
authors.initials: J
authors.lastname: Du
authors.affiliation: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX 75219. E-mail address for H.K.W. Kim: harry.kim@tsrh.org.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kamiya
mesh_terms: D000287:Administration, Topical; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000494:pharmacology*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005270:Femur Head / Q000098:blood supply; D000077557:Ibandronic Acid; D007511:Ischemia / Q000503:physiopathology; D007873:Legg-Calve-Perthes Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010012:Osteogenesis / Q000502:physiology; D011859:Radiography; D013552:Swine; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D004164:Diphosphonates; D000077557:Ibandronic Acid