Laura S. Gregory

Evaluation of the Suchey-Brooks method of age estimation in an Australian subpopulation using computed tomography of the pubic symphyseal surface.

Despite the prominent use of the Suchey-Brooks (S-B) method of age estimation in forensic anthropological practice, it is subject to intrinsic limitations, with reports of differential interpopulation error rates between geographical locations. This study assessed the accuracy of the S-B method to a contemporary adult population in Queensland, Australia and provides robust age parameters calibrated for our population. Three-dimensional surface reconstructions were generated from computed tomography scans of the pubic symphysis of male and female Caucasian individuals aged 15-70 years (n = 195) in Amira and Rapidform. Error was analyzed on the basis of bias, inaccuracy and percentage correct classification for left and right symphyseal surfaces. Application of transition analysis and Chi-square statistics demonstrated 63.9 and 69.7% correct age classification associated with the left symphyseal surface of Australian males and females, respectively, using the S-B method. Using Bayesian statistics, probability density distributions for each S-B phase were calculated, providing refined age parameters for our population. Mean inaccuracies of 6.77 (±2.76) and 8.28 (±4.41) years were reported for the left surfaces of males and females, respectively; with positive biases for younger individuals (<55 years) and negative biases in older individuals. Significant sexual dimorphism in the application of the S-B method was observed; and asymmetry in phase classification of the pubic symphysis was a frequent phenomenon. These results recommend that the S-B method should be applied with caution in medico-legal death investigations of Queensland skeletal remains and warrant further investigation of reliable age estimation techniques.

Bone and prostate cancer cell interactions in metastatic prostate cancer

The interplay in prostate cancer bone metastases between the ‘seed’ (the prostate cancer cells) and the ‘soil’ (the bone microenvironment) has been increasingly recognized as integral to the remarkable tropism for bone shown by prostate cancer. Increasing research into this area is elucidating the mechanisms involved in this complex ‘cross‐talk’. Recent developments, including the use of bisphosphonates in metastatic disease, highlight the important role of bone cells in the development and progression of metastatic prostate cancer. We review the current reports emphasising these possible mechanisms and indicating possible factors for future treatment directions.

Ontogeny of the spheno-occipital synchondrosis in a modern Queensland, Australian population using computed tomography.

Due to disparity regarding the age at which skeletal maturation of the spheno-occipital synchondrosis occurs in forensic and biological literature, this study provides recalibrated multislice computed tomography (MSCT) age standards for the Australian (Queensland) population, using a Bayesian statistical approach. The sample comprises retrospective cranial/cervical MSCT scans obtained from 448 males and 416 females aged birth to 20 years from the Skeletal Biology and Forensic Anthropology Research Osteological Database. Fusion status of the synchondrosis was scored using a modified six-stage scoring tier on an MSCT platform, with negligible observer error (κ = 0.911 ± 0.04, intraclass correlation coefficient = 0.994). Bayesian transition analysis indicates that females are most likely to transition to complete fusion at 13.1 years and males at 15.6 years. Posterior densities were derived for each morphological stage, with complete fusion of the synchondrosis attained in all Queensland males over 16.3 years of age and females aged 13.8 years and older. The results demonstrate significant sexual dimorphism in synchondrosis fusion and are suggestive of intrapopulation variation between major geographic regions in Australia. This study contributes to the growing repository of contemporary anthropological standards calibrated for the Queensland milieu to improve the efficacy of the coronial process for medicolegal death investigation. As a stand-alone age indicator, the basicranial synchondrosis may be consulted as an exclusion criterion when determining the age of majority that constitutes 17 years in Queensland forensic practice.

Breast Cancer Cells Induce Osteolytic Bone Lesions In vivo through a Reduction in Osteoblast Activity in Mice

Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer patients.

Cyclooxygenase-2 Inhibition Delays the Attainment of Peak Woven Bone Formation following Four-Point Bending in the Rat

Fracture healing is retarded in the presence of cyclooxygenase-2 (COX-2) inhibitors, demonstrating an important role of COX-2 in trauma-induced woven bone adaptation. The aim of this experiment was to determine the influence of COX-2 inhibition on the remodeling and consolidation of nontraumatic woven bone produced by mechanical loading. A periosteal woven bone callus was initiated in the right tibia of female Wistar rats following a single bout of four-point bending, applied as a haversine wave for 300 cycles at a frequency of 2 Hz and a magnitude of 65 N. Daily injections of vehicle (VEH, polyethylene glycol) or the COX-2 inhibitor 5,5-dimethyl-3-3(3 fluorophenyl)-4-(4-methylsulfonal)phenyl-2(5H)-furanone (DFU, 2.0 mg · kg−1 and 0.02 mg · kg−1 i.p.), commenced 7 days postloading, and tibiae were examined 2, 3, 4, and 5 weeks postloading. Tibiae were dissected, embedded in polymethylmethacrylate, and sectioned for histomorphometric analysis of periosteal woven bone. No significant difference in peak woven bone area was observed between DFU-treated and VEH rats. However, treatment with DFU resulted in a temporal defect in woven bone formation, where the achievement of peak woven bone area was delayed by 1 week. Woven bone remodeling was observed in DFU-treated rats at 21 days postloading, demonstrating that remodeling of the periosteal callus is not prevented in the presence of a COX-2 inhibitor in the rat. We conclude that COX-2 inhibition does not significantly disrupt the mechanism of woven bone remodeling but alters its timing.

Influence of internal fixator flexibility on murine fracture healing as characterized by mechanical testing and microCT imaging

Mechanically well‐defined stabilization systems have only recently become available, providing standardized conditions for studying the role of the mechanical environment on mouse bone fracture healing. The aim of this study was to characterize the time course of strength recovery and callus development of mouse femoral osteotomies stabilized with either low or high flexibility (in bending and torsion) internal fixation plates. Animals were euthanized and femora excised at 14, 21, and 28 days post‐osteotomy for microCT analysis and torsional strength testing. While a larger mineralized callus was observed in osteotomies under more flexible conditions at all time points, the earlier bridging of the mineralized callus under less flexible conditions by 1 week resulted in an earlier recovery of torsional strength in mice stabilized with low flexibility fixation. Ultimate torque values for these bones were significantly higher at 14 and 21 days post‐osteotomy compared to bones with the more flexible stabilization. Our study confirms the high reproducibility of the results that are achieved with this new implant system, therefore making it ideal for studying the influence of the mechanical environment on murine fracture healing under highly standardized conditions.

Effect of Head Position on Facial Soft Tissue Depth Measurements Obtained Using Computed Tomography.

Facial soft tissue depth (FSTD) studies employing clinical computed tomography (CT) data frequently rely on depth measurements from raw 2D orthoslices. However, the position of each patients head was not standardized in this method, potentially decreasing measurement reliability and accuracy. This study measured FSTDs along the original orthoslice plane and compared these measurements to those standardized by the Frankfurt horizontal (FH). Subadult cranial CT scans (n = 115) were used to measure FSTDs at 18 landmarks. Significant differences were observed between the methods at eight of these landmarks (p < 0.05), demonstrating that high‐quality data are not generated simply by employing modern imaging modalities such as CT. Proper technique is crucial to useful results, and maintaining control over head position during FSTD data collection is important. This is easily and most readily achieved in CT techniques by rotating the head to the FH plane after constructing a 3D rendering of the data.

Introducing Computed Tomography Standards for Age Estimation of Modern Australian Subadults Using Postnatal Ossification Timings of Select Cranial and Cervical Sites

Contemporary, population‐specific ossification timings of the cranium are lacking in current literature due to challenges in obtaining large repositories of documented subadult material, forcing Australian practitioners to rely on North American, arguably antiquated reference standards for age estimation. This study assessed the temporal pattern of ossification of the cranium and provides recalibrated probabilistic information for age estimation of modern Australian children. Fusion status of the occipital and frontal bones, atlas, and axis was scored using a modified two‐ to four‐tier system from cranial/cervical DICOM datasets of 585 children aged birth to 10 years. Transition analysis was applied to elucidate maximum‐likelihood estimates between consecutive fusion stages, in conjunction with Bayesian statistics to calculate credible intervals for age estimation. Results demonstrate significant sex differences in skeletal maturation (p < 0.05) and earlier timings in comparison with major literary sources, underscoring the requisite of updated standards for age estimation of modern individuals.

Morphometric modelling of ageing in the human pubic symphysis: Sexual dimorphism in an Australian population

Despite the prominent use of the pubic symphysis for age estimation in forensic anthropology, little has been documented regarding the quantitative morphological and micro-architectural changes of this surface. Specifically, utilising post-mortem computed tomography data from a large, contemporary Australian adult population, this study aimed to evaluate sexual dimorphism in the morphology and bone composition of the symphyseal surface; and temporal characterisation of the pubic symphysis in individuals of advancing age. The sample consisted of multi-slice computed tomography (MSCT) scans of the pubic symphysis (slice thickness: 0.5mm, overlap: 0.1mm) of 200 individuals of Caucasian ancestry aged 15-70 years, obtained in 2011. Surface rendering reconstruction of the symphyseal surface was conducted in OsiriX(®) (v.4.1) and quantitative analyses in Rapidform XOS™ and Osteomeasure™. Morphometric variables including inter-pubic distance, surface area, circumference, maximum height and width of the symphyseal surface and micro-architectural assessment of cortical and trabecular bone compositions were quantified using novel automated engineering software capabilities. The major results of this study are correlated with the macroscopic ossification and degeneration pattern of the symphyseal surface, demonstrating significant age-related changes in the morphometric and bone tissue variables between 15 and 70 years. Regardless of sex, the overall dimensions of the symphyseal surface increased with age, coupled with a decrease in bone mass in the trabecular and cortical bone compartments. Significant differences between the ventral, dorsal and medial cortical surfaces were observed, which may be correlated to bone formation activity dependent on muscle activity and ligamentous attachments. Our study demonstrates significant sexual dimorphism at this site, with males exhibiting greater surface dimensions than females. These baseline results provide a detailed insight into the changes in the structure of the pubic symphysis with ageing and sexually dimorphic features associated with the cortical and trabecular bone profiles.

Apophyseal ossification of the iliac crest in forensic age estimation: computed tomography standards for modern Australian subadults

This study contrasts the ontogeny of the iliac crest apophysis using conventional radiography and multislice computed tomography (MSCT), providing probabilistic information for age estimation of modern Australian subadults. Retrospective abdominopelvic MSCT data acquired from 524 Australian individuals aged 7–25 and surveillance radiographs of adolescent idiopathic scoliosis patients included in the Paediatric Spine Research Group Progression Study (n = 531) were assessed. Ossification scoring of pseudo‐radiographs and three‐dimensional (3D) volume‐rendered reconstructions using Risser (1958) quantitative descriptors indicate discrepancies in age estimates, stage allocation, and conflicting morphological progression. To mitigate visualization limitations associated with two‐dimensional radiographs, we provide and validate a modified 3D‐MSCT scoring tier of ossification, demonstrating complete fusion between 17.3–19.2 and 17.1–20.1 years in males and females. Legal demarcation for doli incapax presumption and age of majority (18 years) can be achieved using probability estimates from a fitted cumulative probit model for apophyseal fusion using the recalibrated standards.