Thursday, 13 September 2012 to Saturday, 15 September 2012

Influences on fracture healing - a review of the science

Fri14  Sep02:20pm(25 mins)
Where:
Hall 5
Speaker:

Discussion

Bone is both a fascinating structure and organ which can adapt rapidly to its external environment. Its ability to adapt to its surroundings is well known in the horse, where horses used for athletic activities frequently demonstrate issues with both bone adaptation to load, and pathological syndromes where bone fails to adapt, or fails through fracture or microfracture as a result of athletic training.
When a bone fractures, either through a potentially catastrophic displaced fracture, or through a microfracture, which can coalesce to form a stress fracture, a highly orchestrated sequence of events occur, which lead to healing of the damage. It is important that we have a full understanding of this sequence of events, as we have a number of ways to intervene to improve the outcome in such injuries. Many of the events that occur during fracture healing are recapitulation of embryological events that occur during bone development.
Fracture healing can occur through either direct fracture healing or indirect fracture healing. The latter process occurs most commonly naturally where fracture fragments are not well immobilised nor in close apposition. Indirect fracture healing depends on formation of a fibrous and then a fibrochondrogenic callus, which then undergoes osteogenesis to heal the fracture. In direct fracture healing, fracture reduction leads to anatomical reduction of the fracture fragments and rigid internal fixation leads to minimisation of interfragmentary strains. This approach leads to direct regeneration of the haversian system between the fracture fragments, and healing occurs by growth of secondary osteons from one fragment to the other, and by intramembranous bone formation. In direct fracture healing, there is little or no callus formation.
During fracture healing there is a coordinated sequence of events. There is an initial inflammatory response that debrides the fracture site. Subsequently a repair phase produces callus to heal the fracture. Finally the fracture undergoes remodelling when mineralised cartilage is replaced by woven bone and then is remodelled into lamellar bone.
There a wide number of variables that can influence fracture healing, and understanding these variables, and how we can influence them, is important in clinical management of fracture cases. One of the key determinants of fracture healing is the degree of immobilisation and reduction. There is a complex relationship between mechanical loading and fracture healing. Excessive loading coupled with inadequate stabilisation leads to increased interfragmentary strain. It has been known for many years that excessive strain at the site of fractures leads to production of fibrous union, resulting in a delayed or even a non- union. Low strain levels are required for endochondral ossification which is required for fracture healing when a callus is formed. However, it is well documented that bone is an extremely mechanoresponsive tissue, and one of the most potent stimuli for bone formation is loading. Undoubtedly there are periods, soon after fracture occurrence, when fractures require stabilisation and minimal loading; but there is a point when adequate stability is achieved that loading, through controlled exercises is beneficial and can accelerate the repair response. Furthermore, controlled exercise can be beneficial in preventing other fracture associated diseases, for instance osteoarthritis and capsular fibrosis, in cases where there is articular involvement. An understanding of the conflicting stimuli that exercise and loading can cause in fracture healing is vital.
Infection is one of the key contributors to fracture morbidity and mortality in horses. Equine fractures frequently are open, or require lengthy open fracture reduction and stabilisation. Infection is always a risk and contributes greatly to both failure in fracture repair and substantial increase in veterinary costs of treatment. Recent retrospective studies have demonstrated that closed fractures are 4.23 times more likely to remain uninfected and 4.59 times more likely to be discharged from a hospital than open fractures. Risk of infection of fractures can be reduced by appropriate antibiosis, good (and speedy) surgical technique and appropriate debridement of any contaminated or devitalised tissues.
Other issues to be considered during fracture healing include age and size of patient, concurrent systemic disease and the ability to achieve immediate post operative weightbearing.
There are a number of techniques that have been developed to positively influence fracture healing. The use of cancellous bone grafts has been widely used for many years, and can improve osteoinduction by delivery of both cells, growth factors and bone matrix. The use of allogeneic cortical bone grafts are widely used in human orthopaedics, and increasingly used in small animal veterinary orthopaedics, but their use is always going to be very limited in the horse. A number of stimulatory techniques, such as pulsed ultrasound, and the use of electromagnetic and electric fields have been researched and tried in horses, but these approaches have yet to achieve any clinical acceptance, or evidence for clinical efficacy. The use of biodegradable bone cements, therapy with specific growth factors and cytokines (for instance BMP-2 and -7), and the use of mesenchymal stem cells are all receiving current research interest, although none have so far reached mainstream clinical practice.
An understanding of the biological processes underlying fracture healing is crucial in determining the appropriate therapy of fracture patients. Whilst there are novel approaches being developed to hasten fracture healing, the 2 key determinants of fracture healing are related to mechanobiology and infection. The former can be affected by appropriate fixation, adequate reduction and a planned controlled exercise plan during the rehabilitation phase. The latter is best influenced by exemplary surgical technique and the appropriate use of antimicrobials.

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