The Nicolas Andry Award: Modulation of Distraction Osteogenesis in the Aged Rat by Fibroblast Growth Factor

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Abstract
This study explores a series of hypotheses related to modulation of bone formation using the distraction model. The tibial lengthening model was scaled down from dog to rat to use immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction to evaluate cellular events during in vivo bone formation. Different delivery systems such as oral, intragastric, intravenous, subcutaneous, and local diffusion by either extraperiosteal or intramedullary routes, were developed and standardized. Systemic modulators, including diet (total enteral nutrition, calcium, phosphate, soy, whey, casein, lead, and alcohol) and hormones (estrogen, testosterone, growth hormone, and gonadectomy), were tested. To investigate the effects of aging on bone formation, rats of different age groups had tibial lengthening. The aging effect could be distinguished by a reproducible deficiency of endosteal bone formation, consistent with similar deficits in older adult patients having distraction osteogenesis or in patients with senile osteoporosis. Expression of endogenous fibroblast growth factor-2 at the cellular level during the coupled osteogenesis and angiogenesis in young rats was dramatically diminished in old rats. Exogenous fibroblast growth factor-2 reversed the endosteal deficits found in old rats having distraction osteogenesis.

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