Abstract The current benchmark for the assessment of fracture risk is the status of osteoporosis based on the measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). However, DXA-based BMD has been shown to lack predictive ability for individual fracture risk. More than half of the hip fractures occur among people who are not classified as having osteoporosis. Osteoporosis (i.e. reduced bone mass) is only one risk factor for a fracture. In addition to bone mass, the mechanical strength of a bone is influenced by material and structural factors. However, we have limited information about the combined effects of BMD and bone structural properties in the evaluation of fracture risk, with regard to different types of hip fractures in particular. Therefore, this study investigated the radiograph-based structural factors of the upper femur for the assessment of bone mechanical competence and cervical and trochanteric hip fracture risk. The subjects of the clinical study comprised 74 postmenopausal women with non-pathologic cervical or trochanteric hip fracture and 40 age-matched controls. The impact of bone structure on the bone mechanical competence was studied using the experimental material of 140 cadaver femurs. The femora were mechanically tested in order to determine the failure load in a side impact configuration, simulating a sideways fall. In all study series, standard BMD measurements were performed, and the structural parameters of bone were determined from digitized plain radiographs. The present study showed that the large variation in the mechanical competence of bone is associated with the geometrical and architectural variation of bone. Moreover, the results strongly suggested that the etiopathology of different types of hip fractures significantly differs, and that fracture risk prediction should thus be performed separately for the cervical and trochanteric hip fractures. Furthermore, the study implied that the current clinical procedure can better be used for the assessment of the risk of trochanteric fracture, whereas cervical fracture is more strongly affected by the geometrical factors than by BMD. Finally, radiograph-based structural parameters of trabecular bone and bone geometry predicted in vitro failure loads of the proximal femur with a similar accuracy as DXA, when appropriate image analysis technology was used. Thus, the technology may be suitable for further development and application in clinical fracture risk assessment.

Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) is a systemic disorder which includes abnormal bone chemistry, vascular or soft tissue calcification, and abnormal bone formation. Many of the parameters of CKD-MBD have been associated with an increased mortality risk in renal patients. There were three main facets to this research project. The first aim of this research was to perform two different studies using the Chronic Renal Insufficiency Standards Implementation Study (CRISIS) data. This prospective epidemiological study is designed to identify factors associated with renal progression and survival in the pre-dialysis CKD population. We have shown that for each 0.323mmol/L (1mg/dL) increase in serum phosphate there was a significant stepwise increased risk of death. (HR1.3 (1.1, 1.5) P=0.01). The association of baseline phenotypic data against vascular stiffness measurements was also investigated. Augmentation index measured at the radial artery was associated with a raised systolic blood pressure but no association with biochemical abnormalities was found.We hypothesised that the phosphate effect on survival was related to the effects within the CKD-MBD spectrum and therefore control of secondary hyperparathyroidism would improve bone and cardiovascular parameters. Therefore for the second part of this research we performed a randomised controlled trial to examine the effects of cinacalcet with standard therapy compared to standard therapy alone on bone and cardiovascular parameters in haemodialysis patients with uncontrolled hyperparathyroidism. The change of biochemical parameters and cardiovascular markers were also further explored in secondary analyses alongside survival data. The primary end point of change in vascular calcification at 52 weeks showed no significant difference between arms. As equivalent control of phosphate and iPTH was achieved in both arms secondary analyses were performed. This showed a significant regression of left ventricular hypertrophy and carotid intima-media thickness associated with phosphate but not iPTH reduction. Patients whose phosphate reduced during the study had a survival advantage when followed for 5 years (HR=10.2 (1.1, 104.5) P=0.049). The third part of this research was to investigate iPTH assay variability. We explored the variation in iPTH assays across the North West and paired this with regional audit data. This study showed that despite there being significant variation among iPTH assays across the region the variation in clinical management was still accounting for some variation in achieving PTH targets.In conclusion, serum phosphate, within the normal laboratory range, is associated with an increased mortality in CKD patients. Haemodialysis patients may have improvement of cardiovascular outcomes with tight control of secondary hyperparathyroidism, by whichever therapeutic means. Intact PTH assays variation may alter our clinical management but variation in practice still affects guideline achievement.

Introduction: Multiple sclerosis (MS) is associated with impaired bone health in comparison to an equally healthy population, even already in patients at the onset of this disease. The main risk factors for development of osteoporosis in MS patients are known. The aim of the study was to find the relationship of the decrease in bone mineral density (BMD) to the administered cumulative dose of steroids and to other risk factors in MS, mainly to the degree of motor deficit. Further goal was to evaluate the occurence of the risk of low-trauma fractures in multiple sclerosis patients.. The BMD and muscle mass was compared in MS patients (women and men) and control subjects, to examine the effect of main ones - physical disability and long-term glucocorticoid (GC) therapy on BMD. Clinical values of bone remodeling markers were evaluated in assessment of rate of bone loss in patients with multiple sclerosis long term treated with low dose of GC. Patients and methods: We used dual -energy X-ray absorptiometry for a measurement of BMD in 591 MS patients (455 females and 136 males) in 2004 and in cross-sectional longitudinal study published in 2014 with 474 patients (353 women and 121 men). Out of the whole study group body composition was evaluated in 250 MS females, 104 males and 247 healthy controls (193...

Title: The influence of whole-body electromyostimulation on muscle strength and body composition in healthy individuals Objectives: The aim of the diploma thesis is to collect and give comprehensive theoretical information concerning the whole body electromyostimulation topic. Furthermore, find out what the effect of the whole body electromyostimulation method on body weight, fat-free mass, body fat and other parameters of body composition. The aim of this work is to verify whether it is possible to achieve changes in bone mineral density values by means of the WB-EMS method or to increase maximal isometric muscle strength in healthy individuals. Methods: The diploma thesis is an intragroup experiment. The method of qualitative research was used for data collection. Bioelectric impedance analysis was used to evaluate body composition. DXA (Dual Energy X-Ray Absorptiometry) was used to assess bone mineral density and body composition, and isometric muscle strength was evaluated using isometric dynamometry. The research group consisted of 10 young and healthy probands (average age 23.9 years). Probands completed 10 exercise units using the whole body electromyostimulation method. The frequency of exercise was once a week. Results: We have found that after ten weeks of using the whole-body...

Weißbüschelaffen sind häufig verwendete Tiermodelle in der Forschung. Jedoch gibt es zu wenige Untersuchungen zu ihrem Knochenaufbau und Knochenstoffwechsel, um sie auch als Modell auf dem Gebiet der Knochenkrankheiten einsetzen zu können. Somit war es das Ziel dieser Studie, Richtwerte der Knochendichte von Weißbüschelaffen aufzustellen, diese mit denen des Menschen und anderer nichtmenschlicher Primaten zu vergleichen, sowie bestimmte Einflussfaktoren, wie Gewicht, Alter oder hormonelle Umstellungen auf die Knochendichte abzuklären. Desweiteren sollte mittels einer histologischen Darstellung der Knochen, sowie mittels immunhistologischen Nachweisen verschiedener knochenspezifischer Antigene, Gemeinsamkeiten oder Unterschiede zum Menschen im Hinblick auf Veränderungen im Knochen aufgedeckt werden. Abschließend stellte sich dann noch die Frage, ob ein therapeutisches Eingreifen bei niedriger messbarer Knochendichte möglich ist, um die Lebenssituation wieder zu verbessern. Hierzu wurde von 58 C.j. mit Hilfe des Aloka®-CT knochenspezifische Parameter im Bereich des vierten Lendenwirbels (L4) gemessen. Zusätzlich wurde Ca, Pi, AP und Östrogen im Blut bestimmt. Knochenschnitte von L4, Femurkopf/Femurhals und Femurschaft von fünf euthanasierten C.j. (4 männliche, 1 weibliches) wurden histologisch, sowie immunhistologisch (Bestimmung von OPN, OC, RUNX 2, Kollagen Typ 1, Kollagen Typ 5) untersucht. Abschließend wurde bei 2 Tieren eine Therapie mittels Zufütterung von Ca und Vitamin D durchgeführt. Trotz Unterschieden in der Höhe des BMD zum Menschen, konnten Gemeinsamkeiten bei der Reaktion auf Gewichtsveränderungen und Alter festgestellt werden. Eine Zunahme des Gewichts führte zu einer signifikanten Zunahme des BMD. Männliche Weißbüschelaffen zeigten einen Anstieg des BMD bis zu einem Alter von 96 Monaten, was bei Menschen Knochenmassepeak genannt wird, und danach einen signifikanten Abfall. Das bedeutet, dass die Knochen im Alter, genau wie beim Menschen, eine größere Frakturneigung zeigen, als bei jungen Tieren. Desweiteren zeigten Tiere mit einem hohen BMD eine signifikant niedrigere AP, als Tiere mit einem niedrigen BMD. Somit konnte dargestellt werden, dass die AP auch beim C.j. einen Marker für die Osteopenie darstellt. Dies ist ebenfalls eine Gemeinsamkeit mit dem Menschen. Immunhistologisch konnten die Knochenformationsmarker OPN, OC und RUNX 2 nur in den stabilen, bruchfesten Knochen nachgewiesen werden. Kollagen Typ I und V wurden in allen Knochen detektiert. Eine Therapie mittels Ca und Vitamin D bei Tieren mit einem pathologisch niedrigem BMD und klinischen Symptomen, zeigte einen deutlichen Anstieg der Knochendichte nach einem halben Jahr, sowie ein Verschwinden der klinischen Symptome. Schlussfolgernd lässt sich sagen, dass der Weißbüschelaffe trotz unterschiedlicher Knochendichtewerte, ein sehr gutes Tiermodell darstellt zur Untersuchung von Erkrankungen, die sich im Knochen manifestieren (z.B. Osteoporose, Ostemalazie).:Inhaltsverzeichnis Abkürzungsverzeichnis 1 Einleitung 1 2 Literaturübersicht 4 2.1 Der Knochenstoffwechsel 4 2.2 Tiermodelle für Untersuchungen zu Veränderungen im Knochenstoffwechsel 5 2.3 Der Weißbüschelaffe 8 2.4 Computertomografie 9 3 Ergebnisse 3.1 paper 1: “Analysis of the bone metabolism by quantitative computer tomography and clinical chemistry in a primate model (Callithrix jacchus)” (veröffentlicht im Journal of medical primatology 2011) 11 3.2 paper 2: “The conclusiveness of less-invasive imaging techniques (computer tomography, X-ray) with regard to their identification of bone diseases in a primate model (Callithrix jacchus)” (veröffentlicht im Journal of medical primatology 2012) 22 4 Diskussion 4.1 Basiswerte zu computertomografischen Untersuchungen des Knochens des Callithrix jacchus und dessen Vergleichbarkeit mit anderen nichtmenschlichen Primaten sowie mit dem Menschen 31 4.2 Einflussfaktoren auf den Knochenstoffwechsel des Weißbüschelaffen 33 4.3 Beurteilung der Aussagekraft gering invasiver Untersuchungsmethoden anhand histologischer und immunhistologischer Darstellungen von Lendenwirbel und Oberschenkelknochen bei klinisch auffälligen Weißbüschelaffen 39 4.4 Therapie bei auffällig niedriger Knochendichte mit Beeinträchtigungen des Allgemeinverhaltens 44 5 Zusammenfassung 46 6 Summary 48 7 Literaturverzeichnis 50 8 Anhang 8.1 Abstrakt zu einem Poster, vorgestellt auf dem FELASA 2010 Congress vom 14.-17. Juni 2010 in Helsinki 8.2 Abstrakt zu einem Poster (Posterpreis erhalten), vorgestellt auf dem 9. Research Festival for Life Sciences am 17. Dezember 2010 in Leipzig Danksagung

The late second and early third decades of life are critical periods for bone health due to the attainment of peak bone mass during this time, yet little is known about relationships between lifestyle factors and bone health among young-adult females. Therefore, anthropometric, body composition, and nutritional variables were examined in relation to bone mineral density (BMD) and biochemical markers of bone turnover in a group of 60 healthy, young-adult females aged 18 to 25 years. Body weight, body mass index (BMI), fat-free soft tissue mass (FFST), and fat mass had statistically significant and positive associations with BMD. Mean daily dietary protein, magnesium, and iron intakes had statistically significant and negative associations with BMD. A second study compared dietary intake, BMD, and biochemical markers of bone turnover in young-adult females with chronic dieting habits to nondieters. Anthropometric and body composition variables between chronic dieters and nondieters were not statistically different; however, chronic dieters had statistically significantly lower average daily dietary intakes of energy, macronutrients, and selected micronutrients compared to nondieters. Chronic dieters had statistically significantly higher whole body (WB) BMD compared to nondieters. Moderate effects were observed for WB, lumbar spine, trochanter, and total proximal femur BMD such that chronic dieters possessed greater BMD compared to nondieters. It appears that among young-adult females, total body weight, particularly FFST mass, has an important association with BMD. Although nutritional inadequacies among young-adult females raise concerns, overconsumption of nutrients may increase the likelihood of nutrient-nutrient interactions that may have a less than optimal impact on BMD. Future investigations of dietary intake and BMD among young-adult females are warranted. / Master of Science

Selective Serotonin Reuptake Inhibitors and Bone mineral Density in a Population of U.S. Premenopausal Women May 2011 M.S., UNIVERSITY of Massachusetts Amherst Directed by: Professor Elizabeth R. Bertone-Johnson Low bone mineral density (BMD) in post-menopausal women is a risk factor for bone fractures and osteoporosis development. Prior studies in post-menopausal women have shown the use of antidepressant medications, specifically selective serotonin reuptake inhibitors (SSRIs) to be inversely related to BMD. However, the association has not been studied in pre-menopausal women. Current SSRI use is widespread with 8% of U.S. women age 18-44 reporting use. We evaluated the association between SSRIs and BMD and bone mineral content (BMC) cross-sectionally using data from the University of Massachusetts Vitamin D Status Study. SSRI use, diet, and lifestyle factors were assessed by questionnaire. BMD and BMC were measured using dual-energy x-ray absorptiometry (DEXA). The study included 256 women aged 18-30 (mean=21.6 years, SD=4.3 years). In this population, SSRI use was 5%, BMD values ranged from 0.97-1.38 g/cm2 (mean 1.16, SD 0.08), and BMC values ranged from 1833g to 3682g (mean 2541.5, SD=349.2). After adjustment for age, body mass index, and physical activity, mean BMD in the 13 users of SSRIs was 1.15g/cm2 (SD=0.06) compared to 1.16g/cm2 (SD=0.77) in the 243 non-users (p =0.66). After the same adjustments, mean BMC in the 13 users was 2467.1g (SD=285.0) compared to 2547.6g (SD=352.6) in the 243 non-users (p=0.94). Our findings do not support an inverse association between SSRI use and BMD or BMC. However, given the prevalence of SSRI use in young women and the potential for adverse effects on bone health, further study of this association is warranted.

Introduction Inflammatory bowel disease (IBD) and its complications have been well-established. The literature shows an association between IBD and decreased bone mineral density in the adult population. However, most studies have reported an association between IBD and osteoporosis, while the risk of fractures has not been well-studied. The aim of this meta-analysis is to summarize the best available evidence regarding IBS and osteoporotic fractures. Methods A review of the literature using the MEDLINE and EMBASE databases was performed during November 2017. We included cross-sectional and cohort studies that reported the relative risks, odds ratios, and hazard ratios comparing the risk of developing osteoporotic fractures among patients with IBD patients, both ulcerative colitis (UC) and Crohn's disease (CD), versus patients without IBD as controls. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using the generic inverse-variance method. Results After a review of the literature, seven studies fulfilled the eligibility criteria established during the analysis. A significant association was found between IBD and osteoporosis, with a pooled OR of 1.32 (95% CI, 1.2 - 1.4). Low heterogeneity among the studies was found, I=42.3. No publication bias was found using the Egger regression test p=0.18. Sensitivity analysis showed that the inclusion of data on children by Kappelman et al. (2007) did not change the results. Conclusion A significant association between IBD and the risk of developing osteoporotic fractures was observed in this study. There is a 32% increased risk, which is consistent with different cohort studies previously done.

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Objective: This study investigated the behaviors and characteristics of the adult female endurance runner and potential components of the female athlete triad (FAT). The FAT consists of three components that are interrelated: low energy availability, menstrual dysfunction, and low bone mineral density. Low energy availability may occur with or without disordered eating. Reproduction becomes non-essential leading to irregular menstrual cycles. A reduction in estrogen levels may contribute to low bone mineral density which may lead to stress fractures. Research investigating the FAT has primarily focused on adolescent and young adult females. Adult females training for endurance events may also be at risk for the FAT. Method: A survey was constructed and distributed to females in a local half-marathon and marathon training group in Central Florida. The data was collected at one point in time and no additional follow-up was required. The survey aimed to identify specific behaviors and characteristics related to components of the FAT and determine the potential prevalence in a small sample of female endurance athletes aged 18 and older. Results: 72 females with a mean age of 40.92(± 9.61) years completed the survey. Subjects had an average height of 163.60(±6.41) cm, weighed an average of 62.24(±10.05) kg and had 10 years of running experience. Conclusion: Adult female endurance runners demonstrate behaviors and characteristics that may be indicative of the FAT. Participants demonstrated signs of inadvertent or intentional low energy availability. These characteristics can be due to either body dissatisfaction or wanting to increase performance.