title: Osteogenic activity of locally applied small molecule drugs in a rat femur defect model.
abstract: The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT) and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts.
authors.affiliation: Department of Biochemistry & Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Cottrell
authors.forename: Francis M
authors.initials: FM
authors.lastname: Vales
authors.forename: Deborah
authors.initials: D
authors.lastname: Schachter
authors.forename: Scott
authors.initials: S
authors.lastname: Wadsworth
authors.forename: Rama
authors.initials: R
authors.lastname: Gundlapalli
authors.forename: Rasesh
authors.initials: R
authors.lastname: Kapadia
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Connor
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D004195:Disease Models, Animal; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology* / Q000601:surgery; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D008148:Lovastatin; D009853:Omeprazole; D019386:Alendronate