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Fracture Healing

  Fracture Healing:  Four overlapping phases of bone repair: the inflammatory phase; the early callus phase; the mature callus phase; and the remodeling phase.

Inflammatory Phase

  • characterized by an inflammatory and marrow response
  • immediately following fracture to 3 to 4 days postfracture. 
  • release of proinflammatory mediators: interleukin 1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-α):  peak expression 24 hours after injury with decline to baseline levels by 72 hours post-fracture. 

Early Callus Phase

  • predominated by mesenchymal and vascular infiltration and chondrogenesis
  • From few days to several weeks post-fracture 

Mature Callus Phase,

  • marked by endochondral ossification and primary bone (also called immature or woven bone) formation.
  • cartilaginous matrix is mineralized and primary bone is formed
  • fractures are typically considered healed during the late mature callus phase / early remodeling phase. 

Remodeling Phase

  • secondary bone (also called mature or lamellar bone) formation.
  • fractures are typically considered healed during the late mature callus phase / early remodeling phase. 
  • late remodeling can continue beyond 1 year

Chondrogenesis: divided into six phases: MSC proliferation, MSC condensation, chondrocyte formation, chondrocyte maturation, hypertrophic differentiation, and apoptosis.

Parathyroid hormone (PTH)

increases the calcium by indirectly stimulating bone resorption, increasing renal reabsorption of calcium, and increasing intestinal calcium absorption
FDA approved for treatment of osteoporosis in postmenopausal women

  • high-dose recombinant PTH (40 μg) has demonstrated accelerated cortical bridging in distal radius fractures (Aspenberg P, J Bone Miner Res 2010;25(2):404)


Vitamin D (800 IU) and calcium (1 g) has demonstrated increased callus formation in non-op proximal humerus fracture (Doetsch AM, Calcif Tissue Int 2004;75(3):183-188)


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