Background & Aim: Osteoporosis is an important clinical and public health problem through its association with age-related fractures. Compared to women, much less is known about what factors determine age-related bone loss in men. The aim of the work presented in this thesis was to examine the impact of the main steroid hormones, (sex hormones & vitamin D), lifestyle factors and prior fracture on bone health in middle age and elderly men in Europe. Methods: Data presented in this thesis was derived from two large multicentre observational studies: the European Male Ageing Study (EMAS) and the European Prospective Osteoporosis Study (EPOS). In EMAS 3,369 men aged between 40 and 79 years were recruited from 8 European centres for participation in a study of male ageing. They completed a postal questionnaire which included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, from which the parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were obtained, a questionnaire including measures of physical activity, assessment of physical performance and a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX), total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG), 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Dual energy x-ray absorptiometry (DXA) of the hip and lumbar spine and peripheral quantitative computed tomography (pQCT) of the radius at the distal (4%) and midshaft (50%) sites was performed in a subset of two centres. In EPOS, 6,656 men and 7,203 women aged 50 years and over were recruited from population registers in 32 centres. Subjects completed an interviewer administered questionnaire that included questions about previous fractures. Subjects were followed prospectively for a median of 4 years to determine the new occurrence of fractures. A subsample of subjects had bone mineral density measurements performed.Key Results: Based on data from EMAS, free T and both free and total E2 were positively related to the QUS parameters BUA and SOS, while SHBG concentrations were negatively associated. Total and free E2 were negatively associated with β-cTX though not P1NP while PTH was positively associated with both β-cTX and P1NP. Higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine. 25(OH)D was negatively while 1,25(OH)2D positively associated with bone parameters. Higher levels of physical activity and lower physical performance were associated with both higher BUA and SOS. Smoking was associated with lower QUS parameters, while there was a U shaped association with frequency of alcohol consumption. A recalled history of any childhood fracture or forearm fracture was not associated with either bone mass in later life or an increased risk of fracture in men as well as women.Conclusion: Steroid hormones, particularly oestrogen & vitamin D are associated with bone health in middle age and older men. Modification of lifestyle, including increasing physical activity and stopping smoking may help optimise bone strength and reduce the risk of fracture in men. In assessment of future fracture risk a history of childhood fracture does not appear to be important.
|Date of Award
|31 Dec 2014
- The University of Manchester
|Terence O'Neill (Supervisor) & Waquas Waheed (Supervisor)