title: Impregnation of bone chips with alendronate and cefazolin, combined with demineralized bone matrix: a bone chamber study in goats.
abstract: BACKGROUND
  Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk.
  
  
  METHODS
  25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 μg/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting.
  
  
  RESULTS
  Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups.
  
  
  CONCLUSIONS
  A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling.
authors.affiliation: Department of Orthopaedics, Reinier de Graaf Groep, Reinier de Graafweg 3/11, 2625, AD Delft, The Netherlands. N.Mathijssen@rdgg.nl
authors.forename: Nina Mc
authors.initials: NM
authors.lastname: Mathijssen
authors.forename: Gerjon
authors.initials: G
authors.lastname: Hannink
authors.forename: Peter
authors.initials: P
authors.lastname: Pilot
authors.forename: B Wim
authors.initials: BW
authors.lastname: Schreurs
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Bloem
authors.forename: Pieter
authors.initials: P
authors.lastname: Buma
mesh_terms: D019386:Alendronate / Q000008:administration & dosage*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D018775:Bone Demineralization Technique; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016025:Bone Transplantation / Q000379:methods*; D002437:Cefazolin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006041:Goats; D010012:Osteogenesis / Q000187:drug effects; D013249:Sternum / Q000637:transplantation*; D013977:Tibia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D050071:Bone Density Conservation Agents; D002437:Cefazolin; D019386:Alendronate