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  • Review Article
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Fracture healing: mechanisms and interventions

Nature Reviews Rheumatology volume 11, pages 45–54 (2015)Cite this article

Subjects

Key Points

  • Fractures are the most common large-organ, traumatic injuries in humans and approximately 10% do not heal properly

  • Fracture healing involves an anabolic phase of increasing tissue volume, which forms new skeletal tissues, followed by a prolonged catabolic phase in which tissue is remodelled to the original structure

  • Fracture healing is regulated by the nature and extent of trauma, the stability of fracture fixation and biological processes, including immunological and developmental processes associated with skeletal ontology

  • Multiple strategies, involving biophysical, local and systemic cell-based systemic therapies that manipulate the morphogenetic processes that control skeletal development are used to promote healing

  • The two most widely examined therapies for biologically enhancing fracture healing are bone morphogenetic proteins, which act locally, and parathyroid hormone, which acts systemically

  • To advance the field of skeletal healing and to set the stage for developing new local and systemic therapies, conditions for skeletogenic stem cell recruitment and differentiation need to be optimized

Abstract

Fractures are the most common large-organ, traumatic injuries to humans. The repair of bone fractures is a postnatal regenerative process that recapitulates many of the ontological events of embryonic skeletal development. Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, about 10% of fractures will not heal normally. This article reviews the developmental progression of fracture healing at the tissue, cellular and molecular levels. Innate and adaptive immune processes are discussed as a component of the injury response, as are environmental factors, such as the extent of injury to the bone and surrounding tissue, fixation and the contribution of vascular tissues. We also present strategies for fracture treatment that have been tested in animal models and in clinical trials or case series. The biophysical and biological basis of the molecular actions of various therapeutic approaches, including recombinant human bone morphogenetic proteins and parathyroid hormone therapy, are also discussed.

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Figure 1: Histology of early stages of mouse femur fracture repair.
Figure 2: Femur fracture repair.
Figure 3: Crosstalk between Wnt, PTH and BMP signalling in cartilage and bone cell lineages.

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  1. Orthopaedic Surgery, Boston University Medical Centre, Doctor's Office Building Suite 808, 720 Harrison Avenue, Boston, 02118, MA, USA

    Thomas A. Einhorn

  2. Orthopaedic Surgery, Boston University School of Medicine, 72 East Concord Street, E243, Boston, 02118, MA, USA

    Louis C. Gerstenfeld

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T.A.E. and L.C.G. contributed equally to researching data for the article, substantially contributing to discussion of the content, writing the article and to review/editing of the manuscript before submission.

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Correspondence to Thomas A. Einhorn.

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Einhorn, T., Gerstenfeld, L. Fracture healing: mechanisms and interventions. Nat Rev Rheumatol 11, 45–54 (2015). https://doi.org/10.1038/nrrheum.2014.164

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