Detecting microdamage in bone

Abstract

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 calciumrich 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.

Detection of trabecular bone microdamage by micro-computed tomography

“…The use of thin sections results in loss of information regarding the surrounding trabecular structure, limiting the ability to assess the effects of architecture on microdamage formation. Recently, an iodine-based, calcium-chelating contrast agent was used to image a scratch on the surface of a bone sample using micro-computed tomography (micro-CT) (Lee, et al, 2003;Parkesh, et al, 2006). Synchrotron radiation sources can provide very high-resolution images that allow direct visualization of microcracks (Thurner, et al, 2006).…”

Analysis of plastic deformation in cortical bone after insertion of coated and non-coated self-tapping orthopaedic screws

“…Although the methodology for preparing the thin slices for optical microscopy is well-known and documented [21,23,25], there is always the risk of introducing artefacts during the cutting and grinding of thin sections, which is clearly shown in the SEM images. Despite this, by far the most popular method of microcrack detection is transmitted light microscopy [1].…”

“…Local frailty due to stress in a bone may lead to extended healing times or even worse, total failure. The quantification of the extent of microdamage when combined with bone mass measurements can help to predict, and thus prevent, bone failures in patients with osteoporosis [1].…”

“…Microdamage in bone can stimulate bone remodelling by initiating resorption by osteoclasts and new bone formation by osteoblasts [1][2][3][4][5][6][7]. However, extensive bone damage may result in the weakening of internal fixation leading to implant loosening and in some cases total failure.…”

Modern Imaging Technologies in Toxicologic Pathology: An Overview

“…X-ray Imaging and Micro CT: X-ray imaging and micro CT can be useful for visualizing and measuring pathologic alterations of lung and bone micro-architectures (Ritman, 2002;Lee et al, 2003;Barck et al, 2004;Langheinrich et al, 2004a), organ vasculature (Langheinrich et al, 2004b;Ritman, 2005), and morphologic quantification of tumors (De Clerck et al, 2004;Gasser et al, 2005). For instance, as a traditional utilization of X-ray imaging, micro CT is a key approach for evaluation of lung pathology changes such as emphysema in mice (Postnov et al, 2005).…”