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Factors Affecting Fracture Healing

Fracture healing is a complex process. The Factors affecting Fracture Healing include Systemic Factors and Local Factors.

Fracture healing requires the recruitment of appropriate cell (fibroblasts, macrophages, chondroblasts, osteoblasts, osteoclasts) and the subsequent expression of the appropriate genes (those that control matrix production and organization, growth factors, transcription factors) at the right time and in the right anatomical location.

The most important factors in fracture healing after fractures are blood supply and soft-tissue health.

What are the factors affecting bone healing?

Systemic Factors:

  1. Age
  2. Activity level including:
    • General immobilization
    • Space flight
  3. Nutritional status: Protein malnutrition results in negative effects in fracture healing:
    • Decreased periosteal and external callus
    • Decreased callus strength and stiffness
    • Increased fibrous tissue within callus
  4. Hormonal factors:
    • Growth hormone: Increases callus volume.
    • Corticosteroids (microvascular osteonecrosis):Decreases callus proliferation.
    • Others (thyroid, estrogen, androgen, calcitonin, parathyroid hormone, prostaglandins): increases bone remodeling.
  5. Diseases: diabetes, anemia, neuropathies, tabes.
  6. Vitamin deficiencies, A, C, D, K
  7. Drugs: nonsteroidal anti inflammatory drugs (NSAIDs), anticoagulants, factor XIII, calcium channel blockers (verapamil), cytotoxins, diphosphonates, phenytoin, sodium fluoride, tetracycline.
  8. Other substances (nicotine, alcohol): Increase nonunion risk (particularly in the tibia), decrease fracture callus strength and increase pseudarthrosis risk after lumbar fusion up to 500%.
  9. Hyperoxia
  10. Systemic growth factors
  11. Environmental temperature
  12. Central nervous system trauma: Head injury can increase the osteogenic response to fracture.

Nonsteroidal antiinflammatory drugs (NSAIDs) have adverse effects on fracture healing and healing of lumbar spinal fusions (Cyclooxygenase (COX)-2 activity is required for normal enchondral ossification during fracture healing).

Quinolone antibiotics: Toxic to chondrocytes and inhibit fracture healing.

See Also: Fracture Healing

Local Factors Affecting Fracture Healing

A. Factors independent of injury, treatment, or complications:

  1. Type of bone
  2. Abnormal bone
    a. Radiation necrosis: High-dose irradiation causes long-term changes within the haversian system and decreases cellularity.
    b. Infection.
    c. Tumors and other pathological conditions.
  3. Denervation

B. Factors depending on injury:

  1. Degree of local damage:
    a. Compound fracture
    b. Comminution of fracture
    c. Velocity of injury
    d. Low circulatory levels of vitamin K1
  2. Extent of disruption of vascular supply to bone, its fragments (macrovascular osteonecrosis), or soft tissues; severity of injury
  3. Type and location of fracture (one or two bones, e.g., tibia and fibula or tibia alone)
  4. Loss of bone
  5. Soft tissue interposition
  6. Local growth factors

C. Factors depending on treatment:

  1. Extent of surgical trauma (blood supply, heat)
  2. Implant-induced altered blood flow
  3. Degree and kind of rigidity of internal or external fixation and the influence of timing
  4. Degree, duration, and direction of load-induced deformation of bone and soft tissues.
  5. Extent of contact between fragments (gap, displacement, over distraction)
  6. Factors stimulating posttraumatic osteogenesis (bone grafts, bone morphogenetic protein, electrical stimulation, surgical technique, intermittent venous stasis)

D. Factors associated with complications:

  1. Infection
  2. Venous stasis
  3. Metal allergy

Prostaglandins play an important role as mediators of inflammation and COX are required for their production. Inflammation is an essential step in the fracture healing process in which prostaglandin production by COX-2 is involved. Data from animal studies suggest that NSAIDs, which inhibit COX-2, can impair fracture healing due to the inhibition of the endochondral ossification pathway. Animal data suggest that the effects of COX-2 inhibitors are dependent on the timing, duration, and dose, and that these effects are reversible.

COX-2-inhibitors should be considered a potential risk factor for fracture healing, and therefore to be avoided in patients at risk for delayed fracture healing.

References & More

  1. Factors affecting Fracture Healing From Uhthoff HK: Fracture healing. In Gustilo RB, Kyle RF, Templeman DC: Fractures and dislocations, St. Louis, 1993, Mosby.
  2. Sheen JR, Garla VV. Fracture Healing Overview. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551678/
  3. Geusens P, Emans PJ, de Jong JJ, van den Bergh J. NSAIDs and fracture healing. Curr Opin Rheumatol. 2013 Jul;25(4):524-31. doi: 10.1097/BOR.0b013e32836200b8. PMID: 23680778.
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