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dc.contributor.advisorWilliams, John H. H.
dc.contributor.authorBrown, Sharon J.*
dc.date.accessioned2009-06-23T09:00:07Z
dc.date.available2009-06-23T09:00:07Z
dc.date.issued2002-06
dc.identifieruk.bl.ethos.272689
dc.identifier.citationBrown, S.J., Worsfold, M., & Sharp, C.A. Microplate assay for the measurement of hydroxyproline in acid-hydrolyzed tissue samples. BioTechniques, 2001, 30(1), pp. 38-42
dc.identifier.citationBrown, S.J., Pollintine, P., Powell, D.E., Davie, M.W., & Sharp, C.A. Regional differences in mechanical and material properties of femoral head cancellous bone in health and osteoarthritis. Calcified Tissue International, 2002, 71, pp. 227-234
dc.identifier.urihttp://hdl.handle.net/10034/71237
dc.descriptionAppendix 2 is not included as it is two published journal articles
dc.description.abstractOsteoarthritis (OA) is a common musculoskeletal disability and represents a major health burden to society. Pathological changes are found in all tissues of the joint; however studies on bone are few. The aims of this thesis were to characterize some of the densitometric, mechanical and compositional properties of cancellous bone from the Superior (Sup) and Inferior (Inf) regions of human femoral heads, and to compare age-selected healthy bones with those from patients with end-stage OA. From coronal sections of the femoral head, bone cores were drilled out along the anterior-posterior axis and non-adherent fatty tissues removed. Measurements of apparent (PA), true (pj) and volumetric bone mineral density (BMDv) were made prior to determining the ultrasound-derived elastic modulus (Eu) and the compression-derived parameters, compressive modulus (Ec), yield strength (CTY) and yield energy (Wy). From aliquots of powdered bone, calcium and hydroxyproline were determined and a minerahcollagen ratio calculated, and osteocalcin, IGF-I, IGF-II and IGFBP-5 measured by RIA. Another aliquot was processed to remove soft tissue, demineralized in EDTA and the resulting collagen matrix digested with trypsin. From these crude tryptic digests (CTDs), divalently and trivalently (ICTP, IIINTP) crosslinked collagen telopeptides and procollagen propeptides of collagens type I and III were analysed by RIA. PA, BMDv, EC, ay, Wy and EU were systematically increased in cores from the Sup region of both Normal and OA groups (all/KO.05) and reflects differences in loading experienced by this region. In OA bone, PA, BMDv and EU were increased in the Inf region (all/KO.05) possibly as a result of adaptation of the bone to altered loading patterns at the hip. Furthermore, the relationship between EC and PA was different to those in Normals (p=0.019) indicating that other factors, such as architecture, may influence the stiffness of cancellous bone. Of the compositional measures, IGFBP-5 was systematically increased in both regions of OA bone (all /?<0.005) and may be the factor responsible for maintenance of bone mass in OA. The minerahcollagen ratio was decreased in the OA Sup region (p=0.008) indicating undermineralization of bone. In the mineralized matrix of OA bone, concentrations of ICTP:collagencTD and type III collagen antigens were increased in both Sup and Inf regions (all/><0.05) suggesting an increase in type I collagen trivalent crosslinking at the Qtelopeptide and an overall increase in type III collagen respectively. Of the relationships between the various properties, inverse correlations were found between mineral.'collagen and ICTPrcollagenciD ratios (rs= -0.36,/?<0.05) in the OA group indicating increased trivalent collagen crosslinking when bone is under mineralized. In the Normal group PA correlated inversely with IGFBP-5 (rs=-0.64 and -0.72, bothp<0.05) and OC (rs=-0.59,/7=0.056 and -0.71, p<0.05) at both Sup and Inf regions respectively, but were lost in the OA group suggesting loss of regulation at this level in OA. hi conclusion, the cancellous bone in OA femoral heads is denser, but not stiffer than that of Normal bone, and has an altered composition with respect to both structural (ICTP) and regulatory (IGFBP-5) factors which may affect the quality of the bone matrix.
dc.description.sponsorshipFunding support provided by Charles Salt Research Centre and Bone Disease Foundation.
dc.language.isoenen
dc.publisherUniversity of Liverpool (Chester College of Higher Education)
dc.subjectosteoarthritisen
dc.titleStudies in cancellous bone in osteoarthritisen
dc.typeThesis or dissertationen
dc.publisher.departmentCharles Salt Research Centre, Robert Jones & Agnes Hunt Hospital NHS Trust in Oswestryen
dc.type.qualificationnamePhDen
dc.type.qualificationlevelDoctoralen
html.description.abstractOsteoarthritis (OA) is a common musculoskeletal disability and represents a major health burden to society. Pathological changes are found in all tissues of the joint; however studies on bone are few. The aims of this thesis were to characterize some of the densitometric, mechanical and compositional properties of cancellous bone from the Superior (Sup) and Inferior (Inf) regions of human femoral heads, and to compare age-selected healthy bones with those from patients with end-stage OA. From coronal sections of the femoral head, bone cores were drilled out along the anterior-posterior axis and non-adherent fatty tissues removed. Measurements of apparent (PA), true (pj) and volumetric bone mineral density (BMDv) were made prior to determining the ultrasound-derived elastic modulus (Eu) and the compression-derived parameters, compressive modulus (Ec), yield strength (CTY) and yield energy (Wy). From aliquots of powdered bone, calcium and hydroxyproline were determined and a minerahcollagen ratio calculated, and osteocalcin, IGF-I, IGF-II and IGFBP-5 measured by RIA. Another aliquot was processed to remove soft tissue, demineralized in EDTA and the resulting collagen matrix digested with trypsin. From these crude tryptic digests (CTDs), divalently and trivalently (ICTP, IIINTP) crosslinked collagen telopeptides and procollagen propeptides of collagens type I and III were analysed by RIA. PA, BMDv, EC, ay, Wy and EU were systematically increased in cores from the Sup region of both Normal and OA groups (all/KO.05) and reflects differences in loading experienced by this region. In OA bone, PA, BMDv and EU were increased in the Inf region (all/KO.05) possibly as a result of adaptation of the bone to altered loading patterns at the hip. Furthermore, the relationship between EC and PA was different to those in Normals (p=0.019) indicating that other factors, such as architecture, may influence the stiffness of cancellous bone. Of the compositional measures, IGFBP-5 was systematically increased in both regions of OA bone (all /?<0.005) and may be the factor responsible for maintenance of bone mass in OA. The minerahcollagen ratio was decreased in the OA Sup region (p=0.008) indicating undermineralization of bone. In the mineralized matrix of OA bone, concentrations of ICTP:collagencTD and type III collagen antigens were increased in both Sup and Inf regions (all/><0.05) suggesting an increase in type I collagen trivalent crosslinking at the Qtelopeptide and an overall increase in type III collagen respectively. Of the relationships between the various properties, inverse correlations were found between mineral.'collagen and ICTPrcollagenciD ratios (rs= -0.36,/?<0.05) in the OA group indicating increased trivalent collagen crosslinking when bone is under mineralized. In the Normal group PA correlated inversely with IGFBP-5 (rs=-0.64 and -0.72, bothp<0.05) and OC (rs=-0.59,/7=0.056 and -0.71, p<0.05) at both Sup and Inf regions respectively, but were lost in the OA group suggesting loss of regulation at this level in OA. hi conclusion, the cancellous bone in OA femoral heads is denser, but not stiffer than that of Normal bone, and has an altered composition with respect to both structural (ICTP) and regulatory (IGFBP-5) factors which may affect the quality of the bone matrix.


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