Electron Microscopy and Synchrotron analysis of Heterotopic Ossification (HO) from blast-related amputees' has shown that HO is bone with a disorganised structure and altered remodelling. This research performs mechanical testing of HO to understand its biomechanical properties in an attempt to create an accurate model to predict its morphological appearance. The hypothesis of this work is that HO is mechanically mediated in its formation. Synchrotron mechanical analysis of HO samples was performed to measure Young's modulus, ultimate strength and density distribution. A novel algorithm based on Wolf's law was implemented in a Finite Element (FE) analysis model of HO to take into account the differing mechanical and biological properties measured and the presence of HO outside the skeletal system. An HO modeling factor, which considers boundary conditions, and regulates recruitment of the soft tissue into bone formation, results in a re-creatable formation of HO within the soft tissues, comparable to the appearance of HO seen in military amputees. The results and model demonstrates that certain types of HO are under the control of endogenous and exogenous mechanical stimulus. HO can thus be mechanically exploited in the casualty management and rehabilitation process to achieve better clinical outcomes.
Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls. Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression.Objectives
Methods
Heterotopic ossification (HO) is the formation of lamellar bone in extra-skeletal soft tissues. Its exact pathogenic mechanism remains elusive. Previous studies demonstrate observation only of HO at the microscopic scale. This study uses scanning electron microscopy (SEM), Back-scatter electron (BSE) imaging and mechanical testing to detail the organic and non-organic elements of HO, compared to normal bone, to guide stem cell and bio-modelling research into HO. Samples analysed were 5 military blast related HO patients, 5 control cadaveric samples (age and sex matched). Samples were imaged using SEM, BSE and the I13 beam Synchrotron x-ray diffraction scanner using validated quantitative and qualitative techniques of measurement. Appearances seen in HO compared to normal bone were characterised by the presence of a hyper-vascular network and high lacunae (osteocyte) counts, two distinct zones of bone mineral density distribution, with a tendency for hypermineralisation with kurtosis of the grey scale plots (mineral content as a weight percentage of Ca2+ was calibrated to atomic weight of C, Al and HA). Direction of dependence and collagen orientation in HO suggest isotropic properties. This research demonstrates that HO is bone, however its characteristics suggest a high metabolic turnover and disorganised ultra-structure consistent with an inflammatory origin.
