Biomedical subjects

David M L Cooper

Publications and source records attributed to David M L Cooper.

7 recordsLinked to original sources

PubMed2007

Age-dependent change in the 3D structure of cortical porosity at the human femoral midshaft.

Microstructural change associated with cortical bone remodeling has been extensively explored with 2D techniques. However, relatively little is known regarding the 3D dynamic microstructure of cortical bone. Therefore, we employed micro-CT imaging to investigate 3D remodeling-related change in the structure of cortical bone porosity across the human lifespan. Anterior femoral midshaft specimens (n=51 male, 28 female) spanning 18 to 92 years of age were scanned with 7 mum nominal isotropic resolution. Canal volume fraction (Ca.V/TV), mean diameter (Ca.Dm), mean separation (Ca.Sp), degree of anisotropy (DA), connectivity density (Ca.ConnD), and number (Ca.N) were calculated for subperiosteal cylindrical regions of interest. Ca.N was calculated in 2D (Ca.N(2D)) and 3D (Ca.N(3D)). Regression was used to examine the relation between the structural parameters and age. Additionally, the impact of sex, height, and weight were investigated collectively (MANCOVA) and individually (ANCOVA). For all analyses, Ca.V/TV and Ca.Dm were inverted (Ca.V/TV(-1), Ca.Dm(-1)) to establish normality and linear relations with age. Ca.N values (2D and 3D) were non-linearly (quadratic) related to age, increasing until the 6th decade then decreasing. This relation was only significant for the pooled sexes Ca.N(3D) values (p=0.012). Ca.ConnD was positively related to age (p<0.05), while all remaining 3D parameters, except DA for males (p=0.070), were negatively related (p<0.05). In all cases, the relation with age was strongest for females. MANCOVA revealed that age was the only significant (p<0.001) covariate overall. Univariate ANCOVA indicated significant differences between the sexes for Ca.V/TV(-1) and Ca.Dm(-1) (p=0.018 and 0.010, respectively). Relative to males, females had lower values for these parameters, translating into larger mean canal diameter and overall porosity. Body weight had a significant (p=0.043) positive relation with Ca.Dm(-1), indicating lower weight was also associated with increased mean canal diameter. Therefore, while age was the most important factor, sex and body size were found to play a role in parameters related to canal size and the overall level of porosity. This study is unique in that changes in cortical bone microstructure were examined across the adult human lifespan in three rather than two dimensions.

Adolescent↗

PubMed2006

Regional trabecular morphology assessed by micro-CT is correlated with failure of aged thoracic vertebrae under a posteroanterior load and may determine the site of fracture.

INTRODUCTION: Spinal mobilization is commonly used in the treatment of patients with back pain, including individuals with osteoporosis. Previous data indicated that traditional predictors of skeletal failure-lateral or anteroposterior bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) or geometry of the spinous process or vertebral body-do not predict failure load during posteroanterior spinal mobilization. Morphological differences and inhomogeneities in BMD may have important effects on vertebral strength but integral BMD values by DXA cannot reflect these potentially important differences. We investigated the determinants of spinal fracture using muCT. MATERIALS AND METHODS: We measured failure load and failure site in 11 T5-8 cadaveric specimens (mean age 78 years) when a posteroanterior load was applied at the spinous process of T6 using a servohydraulic material testing machine. Radiography and CT scan were used to verify failure site. We observed no damage to the adjacent T7 vertebrae following the T6 posteroanterior failure test. The T7 vertebrae were sectioned to produce regional samples of the spinous process, the lamina and a vertebral body core. Each sample was scanned with muCT to measure bone microarchitectural parameters. We segmented and analysed four trabecular regions (spinous process base and middle, central lamina and central vertebral body). We used one-way repeated measures ANOVA to compare regions and computed Pearson correlations to assess the relation between PA failure load of T6 and the morphological parameters of T7. RESULTS: The BV/TV at the base or middle of the T7 spinous process (fracture sites), Tb.N and Tb.Th at the base were significantly correlated with posteroanterior failure load of T6 (BV/TV base: r=0.74, p=0.01; BV/TV middle: r=0.73, p=0.01; Tb.N base: r=0.64, p=0.03; Tb.Th base: r=0.65, p=0.03). The Tb.Th of the lamina was significantly greater than Tb.Th of the spinous process base (p=0.002). CONCLUSIONS: Whereas previous data indicated that BMD by DXA was not a good predictor of posteroanterior failure load, regional BV/TV of the spinous process base and middle regions, the sites of fracture, are correlated with posteroanterior failure load. Trabecular thickness differed significantly between the base of the spinous process and the lamina, and may have influenced the site of fracture.

Aged↗

PubMed2006

Three-dimensional microcomputed tomography imaging of basic multicellular unit-related resorption spaces in human cortical bone.

This study employed microcomputed tomography (micro-CT) as a novel means for visualizing the morphology and quantifying the range (length) of basic multicellular unit (BMU)-related resorption spaces in human cortical bone. We tested the hypotheses that the density and range of spaces vary with age and sex. The sample included 82 human (18-92 years) anterior femoral midshaft samples. The morphology of the spaces (n = 99) was varied, including unidirectional, bidirectional, branched, and even highly clustered forms. The density of resorption spaces was negatively correlated with age for the combined sexes and females, with Spearman's rho values of -0.355 (P < 0.001) and -0.522 (P = 0.002), respectively. The density of spaces did not differ significantly between the sexes (P = 0.735). Mean range +/- SD for the combined sexes, females, and males was 2,706 +/- 1,177, 2,681 +/- 1,247, and 2,718 +/- 1,150 microm, respectively. Numerical simulation of the effect of the 7,000 microm scan field of view suggested that the actual mean range of the spaces for the pooled sample was actually on the order of 3,770 microm. Range did not correlate significantly with age for the combined sexes (P = 0.587) or females (P = 0.345) and males (P = 0.896) considered separately and was not significantly different (P = 0.883) between the sexes. These results suggest that the range of BMUs is not affected by age. The age-dependent decrease in resorption space density for the females and pooled sexes was most likely a consequence of cortical rarefaction, leading to difficulty detecting resorption spaces with micro-CT, rather than a decrease in overall remodeling activity.

Adolescent↗

PubMed2005

Degenerative knee joint disease in mice lacking 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (Papss2) activity: a putative model of human PAPSS2 deficiency-associated arthrosis.

OBJECTIVE: Murine brachymorphism (bm) results from an autosomal recessive mutation of the Papss2 gene that encodes 3'-phosphoadenosine 5'-phosphosulfate synthetase 2, one of the principal enzymes required for the sulfation of extracellular matrix molecules in cartilage and other tissues. A spondyloepimetaphyseal dysplasia has been identified in Pakistani kindred having a mutation of PAPSS2. In addition to skeletal malformations that include short stature evident at birth due to limb shortening, brachydactyly, and kyphoscoliosis, affected individuals demonstrate premature onset degenerative joint disease. We investigated whether loss of Papss2 activity would similarly lead to degenerative joint disease in mice. METHODS: Mice carrying the bm mutation on a C57BL/6 background were obtained from the Jackson Laboratory. Limbs were analyzed by micro-computed tomography (microCT) and histology. RESULTS: At 12 months of age both male and female bm mice exhibited severe degenerative knee joint disease, with cartilage damage being primarily evident in the patello-femoral and medial compartments. Control 12-14-month-old C57BL/6 mice, in contrast, only occasionally demonstrated minimal cartilage damage. muCT imaging of bm limbs revealed shortened diaphyses associated with flared metaphyses in the proximal elements of both fore and hind limbs. Additionally, the bm hind limbs demonstrated extensive structural alterations, characterized by distortion of the patello-femoral groove, and prominent bowing of both tibia and fibula. CONCLUSIONS: The bm mutant, which develops severe articular cartilage lesions of the knee joint by approximately 12 months of age, represents a novel example of murine degenerative joint disease, possibly representing a model of human PAPSS2 deficiency-associated arthrosis.

Animals↗

PubMed2004

Craniofacial variability and modularity in macaques and mice.

Evolutionary developmental biology of primates will be driven largely by the developmental biology of the house mouse. Inferences from how known developmental perturbations produce phenotypic effects in model organisms, such as mice, to how the same perturbations would affect craniofacial form in primates must be informed by comparisons of phenotypic variation and variability in mice and the primate species of interest. We use morphometric methods to compare patterns of cranial variability in homologous datasets obtained for two strains of laboratory mice and rhesus macaques. C57BL/6J represents a common genetic background for transgenic models. A/WySnJ mice exhibit altered facial morphology which results from reduction in the growth of the maxillary process during formation of the face. This is relevant to evolutionary changes in facial prognathism in nonhuman primate and human evolution. Rhesus macaques represent a nonhuman primate about which a great deal of phenotypic and genetic information is available. We find significant similarities in covariation patterns between the C57BL/6J mice and macaques. Among-trait variation in genetic and phenotypic variances are fairly concordant among the three groups, but among-trait variation in developmental stability is not. Finally, analysis of modularity based on phenotypic and genetic correlations did not reveal a consistent pattern in the three groups. We discuss the implications of these results for the study of evolutionary developmental biology of primates and outline a research strategy for integrating mouse genomics and developmental biology into this emerging field.

Animals↗

PubMed2004

Composition of the founding population of Iceland: biological distance and morphological variation in early historic Atlantic Europe.

We examined the composition of the founding population of Iceland through the study of morphological traits in skeletons from Iceland, Ireland, Norway, and Greenland. This is the first study to address this issue from the Settlement Period of Iceland and contemporary samples from Ireland. We pose the following questions: 1) Was the founding population of Iceland of mixed or homogeneous origin? 2) Is there evidence for a significant Irish cohort in the founding population, as suggested in medieval Icelandic literature? Analysis of biodistance revealed that both Settlement Age and later samples from Iceland showed a greater degree of phenetic similarity to contemporary Viking Age Norwegians than to samples obtained from early medieval Ireland. Analysis of among-individual morphological variation showed that the Settlement Age population of Iceland did not exhibit an increase in variation in comparison to other populations in the sample, suggesting a relatively homogenous origin. However, estimation of admixture between the Irish and Norwegian populations indicated that 66% of the Icelandic settlers were of Norwegian origin. Comparison of the Icelandic samples to hybrid samples produced by resampling the Viking Age Norwegian and early medieval Irish samples revealed that the Icelandic samples are much closer to the Norwegian samples than expected, based on a 66:34 mixture of Norwegian and Irish settlers. We conclude that the Settlement Age population of Iceland was predominantly (60-90%) of Norwegian origin. Although this population was relatively homogenous, our results do not preclude significant contributions from Ireland as well as other sources not represented in our analysis.

Bone and Bones↗

PubMed2003

Imaging skeletal pathology in mutant mice by microcomputed tomography.

OBJECTIVE: We describe the utility of microcomputed tomography ( micro CT) for imaging skeletal abnormalities in rodent model systems. For the purpose of illustration, the progressive ankylosis (ank) mutant was selected. ank mice develop prominent articular and periarticular calcifications at multiple anatomical sites, including paws, elbows, knees, and vertebrae. METHODS: Forelimbs, hindlimbs, and proximal tail vertebrae of 4-month-old female ank/ank mice were scanned at 15 micro m resolution using a SkyScan 1072 micro CT instrument and images were generated using Analyze 4.0 software. RESULTS: This technique was able to show, in 3-dimensional images, the abnormal calcification of ank/ank mice, which was readily observed within joint surfaces, on periosteal surfaces, sesamoid bones, menisci, and joint capsules, as well as other periarticular ligamentous structures. CONCLUSION: As illustrated by the example of the progressive ankylosis mutant, micro CT represents a powerful emerging tool for identifying and monitoring the progression of developmental or acquired skeletal abnormalities within rodent models.

Animals↗