Date of Award

2009

Document type

Thesis

Degree Name

PhD (Doctor of Philosophy)

First Supervisor

Professor T. Clive Lee

Keywords

Osteoporosis, Oestrogens.

Abstract

Population ageing is a pervasive global phenomenon. For the elderly person, maintaining autonomy and independence are key to ensuring quality of life. Osteoporosis is a systemic skeletal disease characterised by low bone density andmicroarchitectural deterioration in bone tissue with a consequent increase in bonefragility. Epidemiological studies have highlighted the burden of disease on patient, society and health service. Dermatoporosis, previously considered a cosmetic and trivial issue, with increasing life expectancy, is a significant cause of morbidity. Theoverall goal of this thesis was to determine the effects of estrogen deficiency and age on bone and skin parameters, and to explore the potential of skin fragility as a surrogate to bone fragility in the diagnosis of osteoporosis.

A successful ovine model of postmenopausal osteoporosis demonstrated significantly increased intracortical bone turnover, albeit in a seasonal manner, in response to estrogen deficiency. This was associated with a compensatory geometrical /structural adaptation of the distribution of bone mass. Estrogen deficiency is associated with a significantly increased intracortical porosity, however there is no adverse effect onbone compression strength at 31 months post ovariectomy. Zoledronic acid decreases bone turnover below that of controls and minimises geometrical /structural adaptation in response to estrogen deficiency.

Geometrical analysis in a human cadaveric cohort demonstrated the effects of age and estrogen deficiency on the adaptive mechanisms in bone, with a concomitant decline in form and function of skin and bone with age. Qualitatively our data indicate that at a tissue level there is minimal difference between the bone of male and female,however the material properties of skin in male and female are significantly different.

Geometrical analysis of the alterations in the periosteal and endosteal surfaces of cortical bone provide us with valuable information regarding the response and adaptation to sex steroid deficiency and age, however they alone do not give usgreater insight into fracture prediction. The relationship between BMD and BR demonstrates that despite the limitations of conventional BMD measurements, they do reflect, to an extent, the geometrical adaptation over time. Our study suggests that acritical balance between BMC and BR exists. Longitudinal analysis of BMD and geometrical changes, specifically buckling ratio and cortical thinning, will in the future provide for stratification of those at risk based on our understanding of howbone mass is redistributed over time.

Raman spectroscopic analysis of bone and skin in an aged human cohort and ovine model of osteoporosis demonstrated common molecular changes in skin and bone. In vivo Raman spectroscopy is a technique likely to develop into a powerful method for future applications. In order to employ the small but significant differencesbetween normal and pathological samples as a diagnostic tool, the present results warrant further investigation and confirmation, to ultimately compile a data bank containing normal and abnormal spectra, combined with appropriate diagnostic algorithms for acceptance into medical practice.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

File Size

23,530 KB

Comments

A thesis submitted to the National University of Ireland in partial fulfilment of the requirement for the degree of Doctor in Philosophy to the Royal College of Surgeons in Ireland, 2009.

Share

COinS