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Osteoporosis, literally meaning 'porous bones', is a disease characterised by low bone mass and micro architectural deterioration of bone tissue. This leads to greater bone fragility with a consequent increase III fracture risk. Postmenopausal women are at greatest risk of this disease, due to the loss of oestrogen at menopause. The overall aim of this thesis was to investigate a multi-mineral supplement rich in calcium (Ca) derived from the red marine algae "Lithothamnion Calcareum" (Aquamin'") in combination with a short-chain fructooligosaccharide (scFOS) (Nutraflora"), on bone mineral density (BMD) and bone turnover markers (BTM) over a two year period in postmenopausal women. An additional aim was to investigate the role of diet in bone health by examining nutritional intake in terms of dietary patterns; and to explore potential lifestyle, dietary and anthropometric predictors ofBMD. To achieve this, a 24-month double-blind randomised controlled trial (RCT) was undertaken in postmenopausal women (n=300) to compare the effects of Aquamin and Nutraflora® combined (CaFOS), Ca alone and non-Ca on BTM and BMD. A total of 300 postmenopausal women were recruited, of which, 214 (71 %) completed the study, with statistical analysis performed on an Intent To Treat Last Observation Carried Forward (ITT-LOCF) dataset. BMD and body composition were measured at baseline and 24 months by dual energy X-ray absorptiometry (DXA); and BTM were measured at baseline, 12 and 24 months by enzyme-linked immunosorbent assays (ELISA). At baseline, health, lifestyle and dietary information were collected, together with anthropometrical measures. Correlation and multiple regression analyses were used to examine the relationship between dietary patterns and BMD; and to investigate potential predictors of BMD. Effects of a combination of Ca and scFOS on total body BMD were observed, compared to Ca alone. Supplementation with CaFOS maintained total body BMD, over 2 years, compared to the Ca alone group. Significantly less bone loss was also seen in women less than 6 years postmenopausal and those with osteopenia. It was also observed that CaFOS had a positive effect on bone turnover through a reduction in bone resorption. CaFOS supplementation appeared to slow the rate of total body bone loss. It was found that a healthy diet, rich in dairy products, fruit and vegetables, which provided high levels of calcium and fibre, may be beneficial for bone health in postmenopausal women. Fat free mass (FFM), which is primarily muscle mass, was found to be a positive predictor of bone health in postmenopausal women, supporting public health messages that advocate maintaining FFM through an active, healthy lifestyle. Overall, findings of this thesis could impact on public health messages which encourage individuals, in particular postmenopausal women, to follow a healthy lifestyle, particularly in relation to diet and exercise. These results provide evidence of the potential beneficial nature of scFOS on BMD in postmenopausal women, with significantly less total body bone loss observed in those taking CaFOS. Future research that examines scFOS independently in postmenopausal women, while accounting for Ca intake, would strengthen the evidence for beneficial effects of scFOS on BMD. Following a healthy diet and lifestyle, combined with scFOS supplementation may play a key role in the prevention of osteoporosis.

Vascular endothelial growth factor (VEGF) has a multifaceted role in bone remodelling influencing early osteoblastogenesis, promoting angiogenesis to aid bone repair and chemo-attraction of several cell types needed for bone formation. Consequently, VEGF is a good candidate for therapeutic strategies in bone healing and sue engineering. The aim of this study was to characterise osteoblast responsiveness to VEGT during osteogenesis.

The aim of this project was to develop and apply image analysis methods to assess the shape and trabecular structure of the femur and determine their relationship with osteoporotic hip fracture.  Changes in bone shape and structure caused by osteoarthritis (OA) were also examined. As osteoporosis (OP) progresses, bone is lost, the skeleton becomes progressively weaker and ultimately fractures.  Fracture risk is generally assessed clinically by bone mineral density (BMD), a measure of bone quantity.  However, the shape and trabecular structure of the bone are also important, but less well-characterised, factors This study applied quantitative measures of shape and structure to medical images of both high (histological sections) and lower resolution (radiographs).  Trabecular structure was analysed using the Fourier transform and was tested first on histological sections.  Principal component, discriminant and neural network analyses were used to generate classifiers that distinguish between control, OP-fracture and OA subjects.  A neural network achieved 84% accuracy, compared with 70% for the best discriminant analysis. Femoral morphology was analysed from radiographs using an active shape model and distinguished between fracture and control groups with an area under the receiver-operating curve (<i>A_z</i>) of 0.81.  Fourier analyses of different regions were compared and the best <i>A_z</i> was 0.93.  Neither shape nor structure measures were correlated with BMD, age or body-mass index (<i>P</i>>0.05).  When these were combined with BMD, <i>A_z</i> increased to 0.99. Further experiments and simulations showed that it might be possible to obtain both shape and texture measures from dual energy x-ray absorptiometry.  Combined with BMD, this would make an improved assessment of fracture risk available to clinicians without requiring additional equipment.