title: Short-term osteoclastic activity induced by locally high concentrations of recombinant human bone morphogenetic protein-2 in a cancellous bone environment.
abstract: METHODS
  An experimental study investigating osteoclastic activity induced by rhBMP-2 in sheep.
  
  
  OBJECTIVE
  To examine the effects of increasing local rhBMP-2 concentration on osteoclastic response and peri-implant bone resorption.
  
  
  BACKGROUND
  Level I clinical studies have established the safe and effective volume and concentration of rhBMP-2 delivered on an absorbable collagen sponge. However, peri-implant bone resorption appearing as decreased mineral density has been observed radiographically in rare instances after implantation of rhBMP-2 on an absorbable collagen sponge (rhBMP-2/ACS).
  
  
  METHODS
  Bilateral corticocancellous defects were created in the distal femora of 30 adult sheep. Combinations of rhBMP-2/ACS implant volume (V) (1V = normal fill or 2V = overfilled) and rhBMP-2 solution concentration (x) (1x = normal concentration or 3.5x = hyperconcentrated) resulted in local rhBMP-2 concentrations of 0x, 1x, 2x, 3.5x, and 7x the estimated effective concentration for this model. Faxitron radiography, quantitative CT, histology, and quantitative histomorphometry were conducted in a blinded fashion to analyze the effect of the treatments.
  
  
  RESULTS
  At 1 week, the normal fill-normal concentration implants (1x) produced the least transient osteoclastic activity resulting in limited peri-implant resorption. Overfilled-hyperconcentrated implants (2x, 3.5x) demonstrated moderate resorption zones. Overfilled-hyperconcentrated implants (7x) demonstrated extensive osteoclastic activity and marked resorption. Results at 4 and 8 weeks revealed dense osteoid and bone in the voids with progressive bony healing. Control defects showed no osteoclastic activity with little to no bony healing.
  
  
  CONCLUSIONS
  Increasing the local rhBMP-2 concentration by overfilling the defect with rhBMP-2/ACS or hyperconcentrating the rhBMP-2 solution on the absorbable collagen sponge led to a concentration-dependent osteoclastic resorption of peri-implant bone. The osteoclastic effect was transient, and progressive healing took place over the 8-week survival period.
authors.affiliation: Department of Orthopaedic Surgery, The Medical College of Wisconsin, Milwaukee, WI 53226-0099, USA. jtoth@mcw.edu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Toth
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boden
authors.forename: J Kenneth
authors.initials: JK
authors.lastname: Burkus
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Badura
authors.forename: Steven M
authors.initials: SM
authors.lastname: Peckham
authors.forename: William F
authors.initials: WF
authors.lastname: McKay
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000166:cytology / Q000000981:diagnostic imaging / Q000601:surgery; D017102:Fracture Healing / Q000187:drug effects; D006801:Humans; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D014057:Tomography, X-Ray Computed
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins