title: Mechanobiological regulation of the remodelling cycle in trabecular bone and possible biomechanical pathways for osteoporosis.
abstract: BACKGROUND
  The rapid loss of trabeculae as observed during osteoporosis is attributed to pathological changes in the bone remodelling process. In this study, it is proposed that osteoporosis is due to altered signals resulting from either (i) a decrease in the mechanosensitivity of the sensor cells or (ii) an increase in the bone tissue elastic modulus.
  
  
  METHODS
  To test these hypotheses, a mechanobiological algorithm was developed and applied to simulate the remodelling cycle in a realistic trabecular strut. The model is based on the supposition that bone resorption is initiated either to remove damaged tissue or when strains fall below a lower threshold; bone formation is triggered when strains exceed an upper threshold.
  
  
  RESULTS
  Applying this algorithm to a realistic trabecula, resorption and subsequent refilling of a cavity was simulated. Results showed that decreases in the mechanosensitivity (simulated by increasing the upper strain threshold) led to under-refilling of cavities. A critical sensitivity was found to exist, above which perforation of the strut due to osteoclastic resorption occurred. It was also found that increases in the bone tissue elastic modulus lead to an increased propensity for trabecular perforation.
  
  
  CONCLUSIONS
  It may be concluded that if cells become less mechanosensitive, or if increases in the elastic modulus of trabecular bone tissue occurs, the possibility of trabecular perforation and therefore the rapid loss of bone mass increases. If this is true, the preservation of the bone mineral content or maintenance of bone cell mechanosensitivity are potential therapeutic strategies for the prevention of osteoporosis.
authors.affiliation: Trinity Centre for Bioengineering, School of Engineering, Trinity College, Dublin 2, Ireland.
authors.forename: Bríanne M
authors.initials: BM
authors.lastname: Mulvihill
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Prendergast
mesh_terms: D000465:Algorithms; D001696:Biomechanical Phenomena; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology*; D003198:Computer Simulation; D004548:Elasticity; D020342:Finite Element Analysis; D006801:Humans; D010024:Osteoporosis / Q000503:physiopathology*; D016012:Poisson Distribution; D015398:Signal Transduction; D013314:Stress, Mechanical