Hyperbaric hyperoxia accelerates fracture healing in mice

PLoS One. 2013 Aug 14;8(8):e72603. doi: 10.1371/journal.pone.0072603. eCollection 2013.


Increased oxygen tension influences bone metabolism. This study comprised two main experiments: one aimed to determine the bone mineral apposition and bone formation rates in vivo under hyperbaric hyperoxia (HBO), and the other aimed to evaluate the effects of exposure to HBO on fracture healing. In experiment 1, male mice were exposed to HBO [90 min/day at 90% O₂ at 2 atmospheres absolute (ATA) for 5 days]. In experiment 2, an open femur fracture model was created in mice, followed by exposure to HBO 5 times/week (90 min/day at 90% O₂ at 2 ATA) for 6 weeks after surgery. In experiment 1, HBO treatment significantly increased the mineral apposition and bone formation rates in the lumbar vertebra and femur and type 1 collagen alpha 1 and alkaline phosphatase mRNA expression in the lumbar vertebra. In experiment 2, at 2 weeks after fracture, the fracture callus was significantly larger in the HBO group than in the non-HBO group. Furthermore, at 4 and 6 weeks after fracture, radiographic findings showed accelerated fracture healing in the HBO group. At 6 weeks after fracture, femur stiffness and maximum load were significantly higher in the HBO group than in the non-HBO group. Urinary 8-hydroxy-2'-deoxyguanosine and plasma calcium concentrations were not significantly different between groups. These results suggest that exposure to HBO enhances bone anabolism and accelerates fracture healing without causing oxidative DNA damage or disruption of plasma calcium homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / genetics
  • Animals
  • Biomechanical Phenomena
  • Blood Chemical Analysis
  • Bone Density
  • Bony Callus / growth & development
  • Collagen Type I / genetics
  • Collagen Type I, alpha 1 Chain
  • Fracture Healing*
  • Gene Expression Regulation
  • Hyperbaric Oxygenation*
  • Insulin-Like Growth Factor I / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteogenesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Urinalysis


  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Alkaline Phosphatase

Grants and funding

This study was supported by a grant-in-aid (no.25350881 to SK) from the Japan Ministry of Education, Culture, Sports, Science, and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.