title: Topical bisphosphonate augments fixation of bone-grafted hydroxyapatite coated implants, BMP-2 causes resorption-based decrease in bone.
abstract: Bone allograft is used in total joint arthroplasties in order to enhance implant fixation. BMPs are known to stimulate new bone formation within allograft, but also known to accelerate graft resorption. Bisphosphonates are strong inhibitor of bone resorption. The aim of this study was to investigate whether the bisphosphonate zoledronate was able to counteract the accelerated graft resorption without interfering with the BMP induced bone formation. In the present study the two drugs alone and in combination were studied in our canine model of impaction bone grafting. We included 10 dogs in this study. Cancellous allograft bone grafts were soaked in either saline or zoledronate solution (0.005mg/mL) and then vehicle or BMP2 (0.15mg rhBMP2) was added. This produced four treatment groups: A) control, B) BMP2, C) zoledronate and D) BMP2+zoledronate. The allograft treated with A, B, C or D was impacted into a circumferential defect of 2.5mm around HA-coated porous Ti implants. Each dog received all four treatment groups with two implants in the distal part of each femur. The group with allograft soaked in zoledronate (C) showed better biomechanical fixation than all other groups (p<0.05). It had less allograft resorption compared to all other groups (p<0.005) without any statistically significant change in new bone formation. The addition of BMP2 to the allograft did not increase new bone formation significantly, but did accelerate allograft resorption. This was also the case where the allograft was treated with BMP2 and zoledronate in combination (D). This caused a decrease in mechanical implant fixation in both these groups compared to the control group, however only statistically significant for the BMP2 group compared to control. The study shows that topical zoledronate can be a valuable tool for augmenting bone grafts when administered optimally. The use of BMP2 in bone grafting procedures seems associated with a high risk of bone resorption and mechanical weakening.
authors.affiliation: Orthopaedic Research Laboratory, Aarhus University Hospital, 8000 Aarhus C, Denmark.
authors.forename: Jorgen
authors.initials: J
authors.lastname: Baas
authors.affiliation: Orthopaedic Research Laboratory, Aarhus University Hospital, 8000 Aarhus C, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Vestermark
authors.affiliation: Orthopaedic Research Laboratory, Aarhus University Hospital, 8000 Aarhus C, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jensen
authors.affiliation: Minneapolis Medical Research Foundation, University of Minnesota, Minneapolis, MN 55415, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Bechtold
authors.affiliation: Orthopaedic Research Laboratory, Aarhus University Hospital, 8000 Aarhus C, Denmark.
authors.forename: Kjeld
authors.initials: K
authors.lastname: Soballe
authors.affiliation: Orthopaedic Research Laboratory, Aarhus University Hospital, 8000 Aarhus C, Denmark. Electronic address: Thomas.Jakobsen@ki.au.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jakobsen
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy* / Q000473:pathology; D016025:Bone Transplantation; D001842:Bone and Bones / Q000473:pathology*; D004164:Diphosphonates / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D006882:Hydroxyapatites / Q000494:pharmacology / Q000627:therapeutic use*; D019736:Prostheses and Implants; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D055396:Bone Morphogenetic Protein 2; D004164:Diphosphonates; D006882:Hydroxyapatites; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2
keywords: Allograft; Bisphosphonate; Bone morphogenetic protein; Implant fixation; Joint replacement