title: Alveolar bone response to submerged bisphosphonate-complexed hydroxyapatite implants.
abstract: BACKGROUND
  In most studies using submerged hydroxyapatite implants, maintenance of alveolar bone after tooth extraction was attempted with plain hydroxyapatite materials. However, clinical results have shown that hydroxyapatite may require biological modification with a bone resorption-inhibiting agent which may be beneficial for maintenance of alveolar bone. We conducted experimental and clinical studies to evaluate the effect of highly bisphosphonate-complexed hydroxyapatite implants on osteoconduction and repair in alveolar bone.
  
  
  METHODS
  Porous hydroxyapatite implants were pre-incubated in 10(-2)M bisphosphonate solutions at pH 3.49. The implants had a diameter of 2.1 mm and a height of 2 mm and adsorbed 115 microg bisphosphonate. Five goats were implanted with 4 plain hydroxyapatite implants on each side of the mandible in root extraction sockets for the precision analysis of dual x-ray absorptiometry (DEXA) measurements. Ten goats were implanted with 4 bisphosphonate/hydroxyapatite implants on one side of the mandible and 4 plain hydroxyapatite implants on the opposite mandible. In a clinical study, 23 bisphosphonate/hydroxyapatite implants were placed in periodontally destroyed tooth root sockets and followed up during one year.
  
  
  RESULTS
  The range for the bone mineral density (BMD) measurement errors for goat histologic sections was 0.48% to 1.03%. There were large differences in peri-implant BMDs in the left and right mandible of the same goat, irrespective as to whether hydroxyapatite or bisphosphonate/hydroxyapatite implants were present. This was due to local anatomical differences typical of alveolar bone. These differences were not significant. Histologically, all bisphosphonate/hydroxyapatite as well as hydroxyapatite controls appeared to be fully integrated and effective as bone replacement material in goat alveolar bone. They exhibited vascularization and osteoconduction of alveolar bone growth along and inside their porous structure. In patients peri-implant healing was clinically and radiographically comparable to plain hydroxyapatite implants. All implants were retained and no dehiscences developed. Radiographically, peri-implant radiolucencies disappeared and alveolar bone was deposited in close proximity to the implants.
  
  
  CONCLUSIONS
  This study contributes to the understanding of the biological properties of hydroxyapatite implants as carriers for the bone-modulating agent bisphosphonate. Our study suggests that normal osteoconduction and repair occurred in alveolar bone around the highly bisphosphonate-complexed hydroxyapatite implants.
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: C
authors.initials: C
authors.lastname: Montanari
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; D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000539:Alveolar Process / Q000187:drug effects; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D001861:Bone Regeneration / Q000187:drug effects*; D003758:Dental Implantation, Endosseous; D015921:Dental Implants; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D004337:Drug Carriers; D004338:Drug Combinations; D017886:Durapatite / Q000494:pharmacology* / Q000627:therapeutic use; D006041:Goats; D006801:Humans; D008334:Mandible; D015999:Multivariate Analysis; D020390:Tooth Socket
chemical_list: D001672:Biocompatible Materials; D015921:Dental Implants; D004164:Diphosphonates; D004337:Drug Carriers; D004338:Drug Combinations; D017886:Durapatite