title: Effects of the systemic administration of alendronate on bone formation in a porous hydroxyapatite/collagen composite and resorption by osteoclasts in a bone defect model in rabbits.
abstract: Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.
authors.affiliation: Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sugata
authors.forename: S
authors.initials: S
authors.lastname: Sotome
authors.forename: M
authors.initials: M
authors.lastname: Yuasa
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: K
authors.initials: K
authors.lastname: Shinomiya
authors.forename: A
authors.initials: A
authors.lastname: Okawa
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016022:Case-Control Studies; D003094:Collagen; D017886:Durapatite / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D010010:Osteoclasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy*; D011817:Rabbits; D011897:Random Allocation
chemical_list: D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents; D003094:Collagen; D017886:Durapatite; D019386:Alendronate