Osteosynthesis and Trauma Care 2002; 10(Suppl 1): S80-S82
DOI: 10.1055/s-2002-33823
© Georg Thieme Verlag Stuttgart · New York

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

F. T. Beil, M. Amling, J. M. Rueger
  • Department of Trauma Surgery, Hamburg University School of Medicine, Hamburg, Germany
Further Information

Publication History

Publication Date:
11 September 2002 (online)


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.


  • 1 Amling M, Priemel M, Holzmann T, Chapin K, Rueger J M, Baron R, Demay M B. Rescue of the skeletal phenotype of vitamin D receptor ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses.  Endocrinology. 1999;  140 4982-4987
  • 2 Bax B E, Wozney J M, Ashhurst D E. Bone morphogenetic protein-2 increases the rate of callus formation after fracture of the rabbit tibia.  Calcif Tissue Int. 1999;  65 83-89
  • 3 Bonnarens F, Einhorn T A. Production of a standard closed fracture in laboratory animal bone.  J Orthop Res. 1984;  2 97-101
  • 4 Ducy P, Amling M, Takeda S, Priemel M, Schilling A F, Beil F T, Shen J, Vinson C, Rueger J M, Karsenty G. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass.  Cell. 2000;  100 197-207
  • 5 Fujimoto R, Tanizawa T, Nishida S, Yamamoto N, Soshi S, Endo N, Takahashi H E. Local effects of transforming growth factor-beta 1 on rat calvaria: Changes depending on the dose and the injection site.  J Bone Miner Metab. 1999;  17 11-17
  • 6 Haberland M, Schilling A F, Rueger J M, Amling M. Brain and bone: central regulation of bone mass. A new paradigm in skeletal biology.  J Bone Joint Surg [Am]. 2001;  83 1871-1876
  • 7 Sakai R, Miwa K, Eto Y. Local administration of activin promotes fracture healing in the rat fibula fracture model.  Bone. 1999;  25 191-196
  • 8 Schilling A F, Priemel M, Beil F T, Haberland M, Holzmann T, Catalá-Lehnen P, Pogoda P, Blicharski D, Müldner C, Löcherbach C, Rueger J M, Amling M. Transgenic and knock out mice in skeletal research. Towards a molecular understanding of the mammalian skeleton.  J Musculoskel Neuron Interact. 2001;  1 275-289
  • 9 Schmidmaier G, Wildemann B, Bail H, Lucke M, Fuchs T, Stemberger A, Flyvbjerg A, Haas N P, Raschke M. Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-β1) from a biodegradable poly(d‚, I-lacide) coating of osteosynthetic implants accelerates fracture healing in rats.  Bone. 2001;  28 341-350
  • 10 Welch R D, Jones A L, Bucholz R W, Reinert C M, Tjia J S, Pierce W A, Wozney J M, Li X J. Effect of recombinant human bone morphogenetic protein-2 on fracture healing in a goat tibial fracture model.  J Bone Miner Res. 1998;  13 1483-1490

Dr. F. T. Beil

Department of Trauma Surgery

Hamburg University School of Medicine

Martinistrasse 52

20246 Hamburg


Email: t.beil@uke.uni-hamburg.de