Osteogenic Activity of Locally Applied Small Molecule Drugs in a Rat Femur Defect Model

Author:

Cottrell Jessica A.12,Vales Francis M.1,Schachter Deborah3,Wadsworth Scott3,Gundlapalli Rama4,Kapadia Rasesh5,O'Connor J. Patrick12

Affiliation:

1. Department of Biochemistry & Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA

2. Graduate School of Biomedical Sciences, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA

3. Center for Biomaterials & Advanced Technologies, Somerville, NJ 08876, USA

4. DePuy Orthopaedics, Inc., Warsaw, IN 46582 , USA

5. Scanco USA, Inc., Wayne, PA 19087, USA

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.

Publisher

Hindawi Limited

Subject

Health, Toxicology and Mutagenesis,Genetics,Molecular Biology,Molecular Medicine,General Medicine,Biotechnology

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