ABSTRACT
Mechanobiology is concerned with the relationships between mechanical forces and biological processes. Bone adapts to altered mechanical loading by modelling and remodelling. Microdamage is a stimulus for adaptation as shown by a sheep overload model. If microdamage accumulates it leads to fracture failure, notably in osteoporosis. Detection methods, based on chelating fluorochromes and radiopaque agents, will enable microdamage to be quantified and, along with bone mass, aid in fracture prediction and prevention. Mechanobiological principles can be utilised to create tissue engineered bone grafts in cases of bone loss due to trauma, malignancy or resorption.
Subject(s)
Adaptation, Physiological/physiology , Bone Remodeling/physiology , Bone and Bones/pathology , Fractures, Bone/etiology , Fractures, Stress/etiology , Osteoporosis/pathology , Weight-Bearing/physiology , Biomechanical Phenomena , Bone Density , Bone and Bones/injuries , Compressive Strength , Connective Tissue , Humans , Models, Biological , Stress, Mechanical , Tissue EngineeringABSTRACT
Fatigue-induced microdamage in bone contributes to stress and fragility fractures and acts as a stimulus for bone remodelling. Detecting such microdamage is difficult as pre-existing microdamage sustained in vivo must be differentiated from artefactual damage incurred during specimen preparation. This was addressed by bulk staining specimens in alcohol-soluble basic fuchsin dye, but cutting and grinding them in an aqueous medium. Nonetheless, some artefactual cracks are partially stained and careful observation under transmitted light, or epifluorescence microscopy, is required. Fuchsin lodges in cracks, but is not site-specific. Cracks are discontinuities in the calcium-rich bone matrix and chelating agents, which bind calcium, can selectively label them. Oxytetracycline, alizarin complexone, calcein, calcein blue and xylenol orange all selectively bind microcracks and, as they fluoresce at different wavelengths and colours, can be used in sequence to label microcrack growth. New agents that only fluoresce when involved in a chelate are currently being developed--fluorescent photoinduced electron transfer (PET) sensors. Such agents enable microdamage to be quantified and crack growth to be measured and are useful histological tools in providing data for modelling the material behaviour of bone. However, a non-invasive method is needed to measure microdamage in patients. Micro-CT is being studied and initial work with iodine dyes linked to a chelating group has shown some promise. In the long term, it is hoped that repeated measurements can be made at critical sites and microdamage accumulation monitored. Quantification of microdamage, together with bone mass measurements, will help in predicting and preventing bone fracture failure in patients with osteoporosis.
