Genetic Concepts and the Küntscher Paradigm: Modulation of Fracture Healing in vivo

Introduction

Fractures are the major clinical problem in trauma and orthopaedic surgery associated with almost any bone disease. Although our means of therapeutic intervention have been significantly improved through the last decades, the biology of fracture healing remains poorly understood. Fracture healing is a complex interaction of hormones, cytokines, extracellular matrix, and several growth factors [2] [5] [7] [9] [10]. Thus, fracture healing should not be viewed in isolation but in the context of skeleton biology.

However, the understanding of complex systems, such as the skeleton itself and its control mechanisms, respectively, sometimes requires simplifications. Models often provide these simplification of some facets of more complex systems. Our understanding of the biology of the skeleton, like that of virtually every other subject in biology, has been transformed by recent advances in human and mouse genetics [4] [6]. Among mammals, mice are the most promising animals for this experimental work [8]. Because extensive genetic information exists, many mouse mutations are known, and cells from early mouse development stages are accessible, scientists have developed transgenic mice, mice in which a gene is introduced or ablated in the germ line. Surprisingly, our understanding of the biology of skeletal repair is still limited. One of the poorly understood questions in this aspect of skeletal biology is: What is the role of bone cell activity, more specifically of osteoclastic bone resorption and osteoblastic bone formation, respectively, in fracture repair? This study aims at addressing the latter aspect by using mice with genetically different bone forming activity. The data presented here demonstrate the successful convergence of molecular genetics with the established and fundamental knowledge of Küntscher intramedullary nailing.

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