title: Skeletal self-repair: stress fracture healing by rapid formation and densification of woven bone.
abstract: Stress fractures of varying severity were created using a rat model of skeletal fatigue loading. Periosteal woven bone formed in proportion to the level of bone damage, resulting in the rapid recovery of whole bone strength independent of stress fracture severity.
  
  
  BACKGROUND
  A hard periosteal callus is a hallmark of stress fracture healing. The factors that regulate the formation of this woven bone callus are poorly understood. Our objective was to produce stress fractures of varying severity and to assess the woven bone response and recovery of bone strength.
  
  
  METHODS
  We used the forelimb compression model to create stress fractures of varying severity in 192 adult rats. Forelimbs were loaded in fatigue until the displacement reached 30%, 45%, 65%, or 85% of fracture. The osteogenic responses of loaded and contralateral control ulnas were assessed 7 and 14 days after loading using pQCT, microCT, mechanical testing, histomorphometry, and Raman spectroscopy.
  
  
  RESULTS
  Loading stimulated the formation of periosteal woven bone that was maximal near the ulnar midshaft and transitioned to lamellar bone away from the midshaft. Woven bone area increased in a dose-response manner with increasing fatigue displacement. Whole bone strength was partially recovered at 7 days and fully recovered at 14 days, regardless of initial stress fracture severity. The density of the woven bone increased by 80% from 7 to 14 days, caused in part by a 30% increase in the mineral:collagen ratio of the woven bone tissue.
  
  
  CONCLUSIONS
  Functional healing of a stress fracture, as evidenced by recovery of whole bone strength, occurred within 2 wk, regardless of stress fracture severity. Partial recovery of strength in the first week was attributed to the rapid formation of a collar of woven bone that was localized to the site of bone damage and whose size depended on the level of initial damage. Complete recovery of strength in the second week was caused by woven bone densification. For the first time, we showed that woven bone formation occurs as a dose-dependent response after damaging mechanical loading of bone.
authors.affiliation: Department of Orthopaedic Surgery, Washington University, St Louis, Missouri 63110, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Uthgenannt
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kramer
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Hwu
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wopenka
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Silva
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology; D002146:Bony Callus / Q000187:drug effects / Q000254:growth & development*; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology*; D015775:Fractures, Stress / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D015898:Tomography Scanners, X-Ray Computed