Background: Reduced bone mineral density (BMD) is an established complication of anorexia nervosa (AN). There is inconclusive evidence as to whether this reduction in bone mass is permanent or can be reversed with recovery from AN. The objectives of this study were to: i. determine the extent of reversal of skeletal deficits with recovery from AN, and the duration of recovery required for complete reversal, if this occurred; and, ii. evaluate the effect of key illness characteristics on BMD. Methods: Women (aged 17-40 years) who had previously received inpatient treatment for AN at one of two hospital-based programs were selected for this cross-sectional study; 514 healthy premenopausal women recruited from the community served as a control group. A detailed lifetime illness history was obtained by a Life History Calendar interview. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the spine, hip and total body. Low BMD was defined as a weight and age-matched standard deviation (Z-score) of ≤ -1.5 at one or more skeletal sites. Participants were considered recovered if they had maintained a body mass index ≥ 18.5 kg/m2 and resumed regular menstruation for ≥ 1 year. Results: Of 190 AN participants, 77 were considered recovered and 113 were ill. The prevalence of low BMD was 11.7% in the recovered group, 47.3% in the ill group and 6.8% in the control group. The odds of low BMD in the recovered participants was significantly lower than in the ill participants (odds ratio [OR] = 0.17, 95% CI 0.07, 0.36, p<0.0001) and was not significantly different from the controls (OR = 1.81, 95% CI 0.79, 3.78, p=0.15). Duration of illness was associated with low BMD (OR = 1.16, 95% CI 1.08, 1.25, p<0.0001) and was negatively associated with the odds of AN recovery. Normal mean BMD values at each skeletal site were observed in women recovered ≥ 3 years. Conclusion: The results emphasize the importance of early and sustained AN recovery for the prevention and treatment of low bone mass in this population and may offer motivation for AN patients to make positive behavioural changes leading to successful, long-term recovery.

Non-invasive estimates of bone quality are of great interest as they could potentially improve the diagnosis and treatments for bone disorders, such as osteoporosis, and could aid in preoperative planning of surgical interventions, improving patient outcomes in orthopaedic trauma. Quantitative computed tomography (QCT) is currently being investigated as a method of estimating structural bone mineral content (sBMC) and, thus, bone quality. However, the reported correlations between QCT and sBMC have been variable and the relationships reported between sBMC and the apparent elastic modulus (E*) of bone have been even more variable. A series of investigations are presented, relating QCT, sBMC, apparent density and the E* of bone. These studies were performed with the ultimate objective of determining the appropriateness of QCT as a predictor of the E* of bone and whether the E* of bone could be predicted from information regarding the sBMC and apparent density. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2008-01-31 22:00:08.77 / This work was funded by the Canadian Institutes of Health Research.

The main focus of bone loss and Osteoporosis (OP) research has been limited almost entirely to women, but OP has become increasingly common in older men and the impact of hip fracture on mortality may actually be greater in men. OP is a major cause of morbidity and mortality in developed countries, at a cost that currently exceeds $10 billion per year in the United States (US) alone. Osteoporotic fractures affect 50 % of women and 20-30% of white men and 4% of black men over the age of 50 years. These statistics may even increase because of increasing life expectancy. Few studies focusing on Blacks have been published to date and very little is known regarding the bone health and the aetiology and prevalence of OP and fractures among older South African blacks. From the above information it is clear that OP is of considerable clinical and economic importance. Without information on the patterns and determinants of bone loss, the formulation of rational prevention and treatment strategies in these groups is not possible. The aim of the study described in this thesis was to investigate the influence of the dietary factors (iron, vitamin C, and protein) and lifestyle factors (alcohol and tobacco smoking) on osteoporotic fractures and bone mineral density in older South African black men using a case-control study design. Sixteen black male patients with fractures of the proximal femur, the proximal humerus or the distal radius and who conformed to the inclusion and exclusion criteria were included in the study. An equal amount of age-matched (K? years), apparently healthy black men with no previous fracture (of the proximal femur and humerus and distal radius), were recruited as a control group. Dual energy X-ray absorptiometry (DEXA) was used for the measurement of the lumbar vertebrae and the proximal femur (hip). Questionnaires were used to gather demographic and medical information, data on physical activity and dietary intakes. Anthropometric measurements and blood samples were taken. Appropriate biochemical analyses were done with standard methods. Both the cases and controls were osteoporotic according to the mean lumbar spine BMD determined in both groups. The BMD was only marginally lower in the cases than in the controls and therefore not statistically significant. The mean tobacco pack years of the cases (13.29) [95% CI: 4.44; 22.141 were almost double that of the controls (7.43) [1.83; 13.031 but it was not statistically significant (p=0.55). Tobacco pack years were negatively associated with BMD of the lumbar spine (p=0.008) even after controlling for possible confounding SUMMARY factors (p=0.001). Malnutrition, as indicated by the low dietary intakes of energy, protein, vitamin C, iron and low BMI, could play a role in the lower bone mineral density (BMD) observed in the cases. The mean protein intakes of the cases (56.1 19) [46.49; 65.741 were very low compared to the recommended 639 per day. This low protein intake was also significantly less compared to the controls (739) [58.28; 88.311. lron intake tended to be lower in the cases compared to the controls (p=0.09). lron intake was not associated with BMD, however, in the stepwise regression analysis; iron intake came out as a possible predictor of BMD of both the lumbar spine and hip, although it was not statistically significant. The BMI was c 19 kg/m2 in 50% of the cases and the controls. S-GGT, a marker of alcohol intake, was significantly increased in the cases with a mean value of 65.88ulL opposed to the 36.33UIL in the control group. S-GGT was the most important predictor of BMD in both the hip and the lumbar spine. There was a significant statistical correlation between lumbar spine BMD (p=0.04); hip BMD (p=0.02) and s-GGT. In conclusion it can be said that malnutrition played a vital role in the low BMD aggravated by the use of tobacco from a young age and alcohol in excessive amounts over weekends. From the results of this study it can be recommended that any intervention programme should focus on alcohol abuse, tobacco smoking and improvement in nutritional status. Children should be encouraged not to smoke and be educated on the detrimental effects of alcohol. It is important to address dietary risk factors associated with OP, namely to increase the overall nutrition of the South African black male with low cost protein and calcium products. Vitamin C enhances iron absorption and may be beneficial for bone collagen. The increased intake thereof by using seasonal fruit can therefore be recommended. / Thesis (M.Sc. (Dietetics))--North-West University, Potchefstroom Campus, 2004.

Bone turnover has important impacts on bone health. The process modifies weak primary woven bone into the strong lamellar bone, repairs damage in bone, and maintains appropriate calcium homeostasis. The process relies heavily on controlled osteoclastic resorption by dissolution of mineral in the area undergoing remodelling. Bone degenerative diseases occur when the balance between bone resorption and deposition of new bone in the turnover process is altered. Bone is a nanocomposite material composed of a mineral phase (calcium phosphate) deposited within an organic matrix. In spite of the intensive research on the subject, the precise molecular structure of the bone mineral is still an open question. The incorporation of citrate within the mineral structure introduced by Davies et al has provide a more comprehensive structural model that could explain many observations in terms of the mineral structure. Based on this new structural model, a hypothesis has been proposed: that other metabolites similar to citrate can be incorporated into the mineral structure, and differences in metabolite incorporation cause fundamental differences in the physical properties of bone mineral. Thus understanding the effect of metabolite incorporation on the physical properties of bone mineral will lead to insight into the molecular mechanisms of bone degenerative diseases and provide a link between bone quality and bone cell function that is currently missing. Chapter 1 provides overview of the bone composite and formation, and changes in its properties during ageing. The development of the mineral structural model is described and the shortcoming of existing models are assessed. Chapter 2 introduces the theoretical foundations of solid-state NMR spectroscopy, which is the primary analytical method employed in this study, followed by specific experimental techniques that have been used in this work. Chapter 3 described the characterisation of seven different OCP-metabolite composites that have been synthesized in this work, and proposes possible structural model for these composites based on an NMR crystallography approach to determine a structural model for one of the synthetic OCP-metabolite compounds, OCP-SUC. In Chapter 4, the dissolution rate of OCP-metabolites is measured in acidic solution to mimic the resorption process by osteoclasts and assess the possible effects of different incorporated metabolites on the solubility of bone mineral. Finally, Chapter 5 summarises the conclusions from the work and suggests the next steps that arise from this work to uncover the complete molecular structure of bone mineral and its variability in disease.

Osteoporosis is a common health problem and it is increasing in prevalence due to the increase in the aging population. The interest to treat osteoporosis has increased in recent years, due to availability of screening modalities, advances in medications that may prevent osteoporotic fractures. Many studies have showed the high medical and economic burden of the disease on the patients, their caregivers and on the health system. Clinical practice guidelines for management of osteoporosis varied nationally and internationally, and the adherence of physicians to guidelines were always reported as suboptimal, though most studies were for after fragility fracture care gap and vert few looked at the primary screening to identify patients at risk before the occurrence of fractures. This thesis is composed of two manuscripts research project assessing the development and impact of screening for osteoporosis guidelines. The first chapter is an overview of osteoporosis, definition, risk factors, diagnosis and treatment. A follow up discussion of the literature on adherence of physicians to the osteoporosis guidelines, which ends up with the rational for this thesis. The first paper is a systematic review to identify guidelines for screening for osteoporosis from 2002-2016 (Chapter 2). We assessed the quality of these guidelines using the AGREE II and IOM standards, compared between the two tools, and assessed if the quality has changed over time. We extracted recommendations in key areas with summary of the systems that were used to assign the level of evidence and strength of recommendations. We found that the quality of guidelines has varied greatly between different countries with no significant change over time. The recommendations and systems for level of evidence were variable and all this may create confusion to clinicians. In the second paper, we used an interrupted time series design to assess the effect of three clinical practice guidelines for screening for osteoporosis in Ontario on the baseline bone mineral density (BMD) testing for older adults 65 years of age and above using administrative data by ICES from 1998-2006. All three guidelines recommend baseline BMD testing for this age population. In addition, we analyzed the pattern of repeated testing in accordance with the latest guideline. We have found low rates of baseline BMD testing with a decreasing pattern of testing. The last guideline in 2010 had gradually increased the trend of BMD testing, though it was a very small change. Stratified analyses by sex showed that the decrease in the total BMD testing is due to decrease in the testing for female population while there is an increasing trend of BMD testing in male population. CPG by Osteoporosis Canada in 2010 caused an immediate reduction in the BMD testing for female, yet, over a period of time, the guideline increased the BMD testing. For male population; the 2002 CPG had immediately increased the BMD testing, while over time this trend has decreased. Despite the low baseline BMD testing by physicians, there is an over use of repeated BMD testing in the low risk population, especially the annual and the 2 yearly BMD repeats. In conclusion: This research project found a varied quality of guideline development and reporting of guidelines for osteoporosis screening, and no improvement in the quality over time (2002-2016). Several systems were used to assign the level of evidence and strength of recommendations with conflicting recommendations between different health organizations in the same country such as in Canada. Many tools are available to appraise the quality of guidelines, however, comparing between two tools (AGREE II & IOM standards) showed that they may give conflicting results for guidelines quality. There is no effect of guidelines for screening for osteoporosis on the ordering of BMD testing to screen adults 65 years and above living in Ontario between 1998- 2016. A small increase the rate of baseline BMD testing followed the release of the 2010 guideline. For male population the 2002 guideline showed an evident immediate and gradual effect over time on the rate of baseline BMD testing ordering for male population. Despite the low baseline BMD testing rates for adults 65 years and above, there is an unnecessary repeated BMD testing for low risk population in Ontario between 2011-2016 which is not in compliance to the latest guideline for screening for osteoporosis.

Recent evidence suggests that declining bone mineral density (BMD) in males is related to declining circulating estrogens. The majority of endogenous plasma estrogens in males result from peripheral aromatization of plasma androgens. Thus, it was hypothesized that dietary supplementation with an aromatizable androgen (androstenedione) may stimulate increases in BMD. BMD (measured by dual energy x-ray absorptiometry) and biochemical markers of bone turnover (1, 25 OH2 Vitamin D, calcitonin, deoxypyrodinoline, and parathyroid hormone) were assessed before and after 12 weeks of dietary androstenedione supplementation (200 mg/d). Twenty-four volunteers were randomized into either an androstenedione supplementation or placebo groups. Study volunteers also performed high intensity resistance training (RT) during the treatment period. Androstenedione supplementation significantly increased plasma estradiol-17β levels by 82%. However, the increase in estradiol-17β did not impact bone turnover. The RT regimen did stimulate significant, local increases in BMD. Spine BMD was significantly increased by 6% for both treatment groups.

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