New model for simulation of fracture repair in full-grown beagle dogs: model characterization and results from a long-term study with ibandronate

Journal of Pharmacological and Toxicological Methods
Frieder BaussGisbert Sponer

Abstract

Given that bisphosphonates reduce bone turnover, it is important to establish that their long-term administration does not impair bone quality. This paper describes a new model for simulation of fracture repair to evaluate several aspects of bone quality following long-term administration (34 or 36 weeks) of ibandronate in full-grown beagle dogs. The treatment schedule consisted of continuous daily subcutaneous administration of a pharmacologically active dose (1 microg/kg/day) and two cyclical intermittent regimens providing a similar total dose per animal at the end of the experiment. Seven or 8 weeks before study end, 10 holes were drilled in the left tibia and bone marrow ablation was performed in the ipsilateral femur. Serial measurements for blood biochemistry (osteocalcin and iso-alkaline phosphatase) and bone mineral density (BMD; whole body and L1-L7) by dual-energy X-ray absorptiometry (DEXA) were performed during the experiment. Bone quality was determined at the end of the experiment by assessing early and late stage defect healing and structural, cellular, and dynamic histomorphometry (femur, tibia, and lumbar vertebrae L3 and L4). Healing of the drill hole defects, which simulate the first stage of fracture healin...Continue Reading

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