The Contribution of Genotype to Heterotopic Ossification after Orthopaedic Trauma

Abstract

Historically, heterotopic ossification (HO) and hypertrophic callus formation has been associated with traumatic brain injury (TBI), spinal cord injury and severe burns. Heterotopic ossification is a distinct skeletal complication (phenotype) in military and civilian trauma patients with high velocity fractures. Despite an incidence of 11-25% in multiply injured civilian patients and patients, and 63% in combat related amputations, the phenomenon is still poorly understood. Data suggests that bone remodeling is subject to significant autonomic control via beta-2 (beta-2) adrenergic receptors on osteoblasts and involves the hormone leptin. Patients with multiple trauma and/or brain injury frequently have autonomic nervous system dysfunction but the potential link to heterotopic bone formation has not yet been studied. Furthermore, not all patients with similar injury patterns and demographics develop HO, suggesting a genetic component, which under the appropriate environmental and physiologic conditions, predisposes some patients to the complication. The process of heterotopic bone formation around fractures and ectopic bone around joints and soft tissue unrelated to trauma appear to be the same phenomenon. This created a unique opportunity to prospectively monitor patients with traumatic fractures using serial radiographs for heterotopic bone formation and to match these with controls based on demographics and injuries. We have now examined 1095 patients over a two year period for HO and single nucleotide polymorphisms that may be associated with HO. Certain individuals are genetically predisposed to complications which may be triggered by environmental influences. While this phenomenon is often associated lung cancer and cigarette smoke, there is also evidence of genetic predisposition to common skeletal diseases such as osteoporosis.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2009
Accession Number
ADA615342

Entities

People

  • Erika J. Mitchell

Organizations

  • Vanderbilt University Medical Center

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Brain Injuries
  • Central Nervous System
  • Congenital Hereditary And Neonatal Diseases And Abnormalities
  • Diseases And Disorders
  • Genes
  • Genetic Phenomena
  • Genetic Structures
  • Genetics
  • Genotypes
  • Heterotopic Ossification
  • Musculoskeletal System
  • Nervous System
  • Osteogenesis
  • Phenotypes
  • Spinal Cord
  • Wounds And Injuries

Fields of Study

  • Medicine

Readers

  • Molecular and Cellular Biology
  • Neurotrauma and Rehabilitation Medicine.
  • Trauma Surgery or Emergency Medicine.

Technology Areas

  • Biotechnology