title: Bone augmentation using a new injectable bone graft substitute by combining calcium phosphate and bisphosphonate as composite--an animal model.
abstract: OBJECTIVE
  The aim of this study was to create a new injectable bone graft substitute by combining the features of calcium phosphate and bisphosphonate as a composite bone graft to support bone healing and to evaluate the effect of alendronate to the bone healing process in an animal model.
  
  
  METHODS
  In this study, 24 New Zealand white rabbits were randomly divided into two groups: a calcium phosphate alendronate group and a calcium phosphate control group. A defect was created at the proximal medial tibia and filled with the new created injectable bone graft substitute calcium phosphate alendronate or with calcium phosphate. Healing process was documented by fluoroscopy. To evaluate the potential of the bone graft substitute, the proximal tibia was harvested 2, 4, and 12 weeks after operation. Histomorphological analysis was focused on the evaluation of the dynamic bone parameters using the Osteomeasure system.
  
  
  RESULTS
  Radiologically, the bone graft materials were equally absorbed. No fracture was documented. The bones healed normally. After 2 weeks, the histological analysis showed an increased new bone formation for both materials. The osteoid volume per bone volume (OV/BV) was significantly higher for the calcium phosphate group. After 4 weeks, the results were almost equal. The trabecular thickness (Tb.Th) increased in comparison to week 2 in both groups with a slight advantage for the calcium phosphate group. The total mass of the bone graft (KEM.Ar) and the bone graft substitute surface density (KEM.Pm) were consistently decreasing. After 12 weeks, the new bone volume per tissue volume (BV/TV) was still constantly growing. Both bone grafts show a good integration. New bone was formed on the surface of both bone grafts. The calcium phosphate as well as the calcium phosphate alendronate paste had been enclosed by the bone. The trabecular thickness was higher in both groups compared to the first time point.
  
  
  CONCLUSIONS
  Calcium phosphate proved its good potential as a bone graft substitute. Initially, the diagrams seem to show a tendency that alendronate improves the known properties of calcium phosphate as a bone graft substitute. The composite graft induced a good and constant new bone formation. Not only the graft was incorporated into the bone but also a new bone was formed on its surface. But we could not prove a significant difference between the grafts. Both implants proved their function as a bone graft substitute, but the bisphosphonate alendronate does not support the bone healing process sufficiently that the known properties of calcium phosphate as a bone graft substitute were improved in the sense of a composite graft. In this study, alendronate used as a bone graft in a healthy bony environment did not influence the bone healing process in a positive or negative way.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. c.schlickewei@uke.de.
authors.forename: Carsten W
authors.initials: CW
authors.lastname: Schlickewei
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Laaff
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Andresen
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Till O
authors.initials: TO
authors.lastname: Klatte
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Rueger
authors.affiliation: Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, 45117, Essen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Ruesing
authors.affiliation: Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, 45117, Essen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Epple
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000008:administration & dosage*; D016025:Bone Transplantation / Q000379:methods*; D002130:Calcium Phosphates / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D023421:Models, Animal; D011817:Rabbits; D011859:Radiography; D013977:Tibia / Q000000981:diagnostic imaging* / Q000187:drug effects
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; D004164:Diphosphonates; C020243:calcium phosphate