title: Manipulating the anabolic and catabolic response in bone graft remodeling: synergism by a combination of local BMP-7 and a single systemic dosis of zoledronate.
abstract: Remodeling of a bone graft can be influenced both by anabolic substances, such as a bone morphogenic protein (BMP) and by anticatabolic substances, such as the bisphosphonates. BMPs are potent bone anabolic substances, but also boost catabolism and cause resorption. Bisphosphonates inhibit osteoclast function and can be used to postpone resorption. In the present study a combination of both drugs was explored in a rat bone chamber model. Cancellous bone grafts were treated with either BMP-7 or saline and placed in a bone chamber implanted in the proximal tibia. After 2 weeks, an injection of either zoledronate 0.1 mg/kg or saline was given subcutaneously. The rats were killed after 6 weeks, and bone ingrowth distance into the graft and graft resorption were measured by histomorphometry. BMP-7 significantly (p = 0.007) increased new bone ingrowth distance into the graft from 2.0 mm (SD = 0.98 mm) in the controls to 3.1 mm (SD = 0.93 mm). If bisphosphonate was not given, most of the newly formed and old graft bone was resorbed. A single injection of zoledronate significantly (p < 0.001) increased the trabecular volume/total volume to 40% (SD = 9%) compared to 14% (SD = 10%) in the nonbisphosphonate treated. In total, the net amount of bone increased by 400% when BMP-7 and zoledronate combined was compared to saline. A bone graft can be treated with BMP-7 to increase new bone formation and at the same time be protected against premature catabolism by a single dose of a bisphosphonate. This combination might be useful in various conditions in orthopedic reconstruction.
authors.affiliation: Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Anna Kajsa
authors.initials: AK
authors.lastname: Harding
authors.forename: Per
authors.initials: P
authors.lastname: Aspenberg
authors.forename: Masashi
authors.initials: M
authors.lastname: Kataoka
authors.forename: David
authors.initials: D
authors.lastname: Bylski
authors.forename: Magnus
authors.initials: M
authors.lastname: Tägil
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects*; D016025:Bone Transplantation / Q000502:physiology*; D004164:Diphosphonates / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D000077211:Zoledronic Acid
chemical_list: C525821:Bmp7 protein, rat; D050071:Bone Density Conservation Agents; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D007093:Imidazoles; D016212:Transforming Growth Factor beta; D000077211:Zoledronic Acid