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Investigation of femoral head osteonecrosis would benefit from an animal model whose natural history includes progression to bony collapse of a segmental necrotic lesion. The bipedal emu holds attraction for systematic organ-level study of collapse mechanopathology. One established method of experimentally inducing segmental lesions is liquid nitrogen cryoinsult. Four cryoinsult parameters-hold temperature, freeze duration, freeze/thaw repetition, and thaw duration-were investigated to determine their individual and combined effects on resulting necrotic lesion morphology. 3D distributions of histologically apparent osteocyte necrosis from 24 emus receiving varying cryoinsults were used to develop univariate and multivariate linear regression models relating resulting necrotic lesion morphology to particular cryoinsult input parameters. These models were then applied to predict lesion size in four additional emus receiving differing input cryoinsults. The best multivariate regression model predicted lesion volumes that were accurate to better than 8% of overall emu femoral head volume. The hold temperature during cryoinsult was by far the most influential cryoinsult input parameter. The utility of this information is to enhance the consistency and predictability of cryoinsult-induced segmental lesion size for the purposes of systematic laboratory studies at the whole-organ level. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:931-937 [ABSTRACT FROM AUTHOR]

Abstract: Cryoinsult-induced osteonecrosis (ON) in the emu femoral head provides a unique opportunity to systematically explore the pathogenesis of ON in an animal model that progresses to human-like femoral head collapse. Among the various characteristics of cryoinsult, the maximally cold temperature attained is one plausible determinant of tissue necrosis. To identify the critical isotherm required to induce development of ON in the cancellous bone of the emu femoral head, a thermal finite element (FE) model of intraoperative cryoinsults was developed. Thermal material property values of emu cancellous bone were estimated from FE simulations of cryoinsult to emu cadaver femora, by varying model properties until the FE-generated temperatures matched corresponding thermocouple measurements. The resulting FE model, with emu bone-specific thermal properties augmented to include blood flow effects, was then used to study intraoperatively performed in vivo cryoinsults. Comparisons of minimum temperatures attained at FE nodes corresponding to the three-dimensional histologically apparent boundary of the region of ON were made for six experimental cryoinsults. Series-wide, a critical isotherm of 3.5°C best corresponded to the boundary of the osteonecrotic lesions. [Copyright &y& Elsevier]

Systematic studies of treatment options for femoral head osteonecrosis have been hindered by the lack of an animal model that mimics the human event of femoral head collapse. The (bipedal) emu model of osteonecrosis has proven to progress to collapse following an external insult. Since osteonecrosis clinically has multiple etiologies, various alternatives are seemingly appropriate to initiate lesions for research purposes. This study compared osteonecrosis initiated by a local cryoinsult, to that initiated by a large systemic dose of steroid (methylprednisolone acetate), and by a combination of steroid and cryoinsult. One year post-insult, the animals were sacrificed and their femoral heads harvested. A custom-written computer program was used to expedite analysis of the global distribution of histologically apparent osteonecrosis, as determined by the Ficat scale. Following whole-head analysis, grade distributions were calculated, and a measure of spatial clustering of histologic abnormality was calculated using Moran's I statistic. Normal femoral heads showed very small amounts of histological abnormality, and no significant spatial clustering. Femoral heads receiving isolated cryoinsult had a greater incidence of high-grade abnormality, as well as statistically significant spatial clustering of that abnormality. Steroid-only animals had a higher percentage of diffuse, low-grade abnormality. The group receiving both steroid and cryoinsult showed the highest overall abnormality, with statistically significant clustering of that high-grade abnormality. Cryoinsult, both in isolation and in combination with a steroid regimen, appeared necessary to mimic the clinically typical focal lesions of osteonecrosis. [ABSTRACT FROM AUTHOR]