title: Normal osteoconduction and repair in and around submerged highly bisphosphonate-complexed hydroxyapatite implants in rat tibiae.
abstract: BACKGROUND
  Ceramic hydroxyapatite implants have been used in dentistry for their unique compatibility with alveolar bone. Recently it was reported that bisphosphonates may be beneficial in preventing alveolar bone destruction associated with natural and experimental periodontal disease. Furthermore, bisphosphonate does prevent resorption of alveolar bone following mucoperiosteal flap surgery. We undertook a preliminary study evaluating the effects of highly bisphosphonate-complexed hydroxyapatite implants on osteoconduction and repair in rat tibiae.
  
  
  METHODS
  Porous hydroxyapatite implants were pre-incubated in 10(-2)M bisphosphonate solutions at pH 3.49 and pH 7.32. The implants had a diameter of 2.1 mm and a height of 2 mm and adsorbed 115 microg bisphosphonate in vitro. Bisphosphonate/hydroxyapatite implants and plain hydroxyapatite implants were inserted in opposite tibial metaphyses of 35 rats. The measurement errors for the mineral density (MD) of the implants and the proximal trabecular mineral bone density (TD) were estimated by peripheral computed tomography and the bone mineral density (BMD) measurement error by dual x-ray absorptiometry.
  
  
  RESULTS
  The measurement errors for the MD of the implants and the TD by peripheral computed tomography were 0.81% and 1.96%, respectively ex vivo. The BMD measurement error estimated by dual x-ray absorptiometry was 0.51% ex vivo. TD and BMD for bisphosphonate/hydroxyapatite implants were insignificantly higher compared to plain hydroxyapatite implants. Bisphosphonate/hydroxyapatite pre-incubated at pH 7.32 were found to be nondegradable implants, while bisphosphonate/hydroxyapatite (pH 3.49) implants were slowly degradable and lost a significant 5% of their density. Histologically, all bisphosphonate/hydroxyapatite implants appeared to be fully integrated and effective as bone replacement material in rat tibial bone. They exhibited vascularization and osteoconduction of tibial bone growth along and inside their porous structure.
  
  
  CONCLUSIONS
  Our study suggests that normal osteoconduction and repair occurred in and around the highly bisphosphonate-complexed hydroxyapatite implants in rat tibiae.
authors.affiliation: Department of Oral Function and Implantology, Academic Center for Dentistry, Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Denissen
authors.forename: R
authors.initials: R
authors.lastname: Martinetti
authors.forename: A
authors.initials: A
authors.lastname: van Lingen
authors.forename: A
authors.initials: A
authors.lastname: van den Hooff
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D001861:Bone Regeneration / Q000187:drug effects*; D001862:Bone Resorption / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D004337:Drug Carriers; D004338:Drug Combinations; D017886:Durapatite / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006863:Hydrogen-Ion Concentration; D020007:Implants, Experimental; D015999:Multivariate Analysis; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia; D014057:Tomography, X-Ray Computed
chemical_list: D001672:Biocompatible Materials; D004164:Diphosphonates; D004337:Drug Carriers; D004338:Drug Combinations; D017886:Durapatite