title: Sclerostin antibody treatment improves implant fixation in a model of severe osteoporosis.
abstract: BACKGROUND
  The mechanical fixation of orthopaedic and dental implants is compromised by diminished bone volume, such as with osteoporosis. Systemic administration of sclerostin antibody (Scl-Ab) has been shown to enhance implant fixation in normal animals. In the present study, we tested whether Scl-Ab can improve implant fixation in established osteoporosis in a rat model.
  
  
  METHODS
  We used an ovariectomized (ovx) rat model, in which we found a 78% decrease in trabecular bone volume at the time of implant surgery; sham-ovx, age-matched rats were used as controls. After placement of a titanium implant in the medullary cavity of the distal aspect of the femur, the rats were maintained for four, eight, or twelve weeks and treated biweekly with Scl-Ab or with the delivery vehicle alone. Outcomes were measured with use of microcomputed tomography, mechanical testing, and static and dynamic histomorphometry.
  
  
  RESULTS
  Scl-Ab treatment doubled implant fixation strength in both the sham-ovx and ovx groups, although the enhancement was delayed in the ovx group. Scl-Ab treatment also enhanced bone-implant contact; increased peri-implant trabecular thickness and volume; and increased cortical thickness. These structural changes were associated with an approximately five to sevenfold increase in the bone-formation rate and a >50% depression in the eroded surface following Scl-Ab treatment. Trabecular bone thickness and bone-implant contact accounted for two-thirds of the variance in fixation strength.
  
  
  CONCLUSIONS
  In this model of severe osteoporosis, Scl-Ab treatment enhanced implant fixation by stimulating bone formation and suppressing bone resorption, leading to enhanced bone-implant contact and improved trabecular bone volume and architecture.
  
  
  CONCLUSIONS
  Systemic administration of anti-sclerostin antibodies might be a useful strategy in total joint replacement when bone mass is deficient.
authors.affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, 600 South Paulina Street, Suite 507, Chicago, IL 60612. E-mail address for A.S. Virdi: amarjit_virdi@rush.edu.
authors.forename: Amarjit S
authors.initials: AS
authors.lastname: Virdi
authors.affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, 600 South Paulina Street, Suite 507, Chicago, IL 60612. E-mail address for A.S. Virdi: amarjit_virdi@rush.edu.
authors.forename: John
authors.initials: J
authors.lastname: Irish
authors.affiliation: Department of Periodontology, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sena
authors.affiliation: Metabolic Disorders, Amgen, Inc., One Amgen Center Drive, 29-1-A, Thousand Oaks, CA 91320.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Metabolic Disorders, Amgen, Inc., One Amgen Center Drive, 29-1-A, Thousand Oaks, CA 91320.
authors.forename: Hua Zhu
authors.initials: HZ
authors.lastname: Ke
authors.affiliation: Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Skip Bertman Drive, Baton Rouge, LA 70803.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: McNulty
authors.affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, 600 South Paulina Street, Suite 507, Chicago, IL 60612. E-mail address for A.S. Virdi: amarjit_virdi@rush.edu.
authors.forename: Dale R
authors.initials: DR
authors.lastname: Sumner
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000276:immunology; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers / Q000276:immunology; D016348:Osseointegration / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000150:complications*; D010052:Ovariectomy; D011475:Prosthesis Failure / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000906:Antibodies; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat