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

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.

No description available.

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.

No description available.

Obesity is a worldwide epidemic increasing at an alarming rate among youth who are facing similar health problems as adults. Sleep Apnea Syndrome (SAS) is an underdiagnosed comorbidity of obesity, characterized by repetitive nocturnal interruptions in breathing. Obesity is associated with delayed skeletal maturation in overweight youth, but mechanisms contributing to this problem are unclear. Obesity and SAS both have been shown to disrupt regulatory hormones and cytokines that influence bone accretion during adolescence. PURPOSE: The purpose of this study was to assess the combined effects of excess body weight and SAS on bone mineral density (BMD) and content (BMC), bone turnover, and on the regulatory hormones leptin and IGF-1 known to potentially influence bone accretion during adolescence. METHODS: Men aged 18-28 years were assigned to groups as follows: normal weight controls (CON: AHI <3, n=8); overweight without SAS (OWT: BMI < 26 kg/m2 and AHI <3, n=9); and overweight with SAS (SAS: BMI >26 kg/m2 and AHI >5, n=8). The apnea/hypopnea index (AHI) expresses the score for disrupted nighttime breathing events/hr and was obtained in this study with results from a home sleep screening test. Health history and Epworth Sleepiness Scale (ESS) questionnaires also were administered. Bone mineral parameters and body composition variables were measured with dual-energy X-ray absorptiometry. Serum osteocalcin, leptin, IGF-1, and NTx-1 were measured, respectively, by radioimmunoassay and enzyme-linked immunoabsorbent assay. RESULTS: Fat-free mass, intra-abdominal fat, and fat mass were higher in the SAS and OWT groups (p<0.03). ESS scores revealed that SAS individuals were sleepier than CON and OWT groups (p<0.009). Total body and site-specific BMD and BMC values (lumbar spine, hip, and forearm) were similar between groups and did not relate to the estimated AHI score. Serum OC and NTx-1 did not differ between groups. Leptin levels were 30% higher in OWT and SAS than in the CON group (p<0.02), but did not correlate with the AHI score. Across all subjects (n=25), only lumbar spine BMC (p<0.005) was correlated to AHI (r=-.52; p<0.01). The preponderance of this relationship between AHI and lumbar spine BMC was attributable to the close inverse association of these two variables within the SAS group (r = -.81; p<0.001). CONCLUSION: The effects of SAS were not influenced by the amount of whole-body, intra-abdominal adiposity or lean body mass. Neither leptin nor IGF-1 predicted bone status across all groups. Daytime fatigue and sleepiness, a cardinal symptom of SAS, combined with overweight may contribute to lower lumbar BMC by chronically reducing weight-bearing physical activity and thereby reduce exposure time for mechanical loading of the spine in affected individuals. Further research is needed to explore the biochemical, physiological, and apparently the physical activity implications of SAS on skeletal status and turnover. / Master of Science

This thesis is based on studies of the ten-year community-based intervention programme entitled, the Vadstena Osteoporosis Prevention Project (VOPP). The specific aims of the research were to describe the effects of physical activity and training programmes on bone mass and balance performance in adults, to determine whether a fall risk prevention programme could motivate personal actions among the elderly, to ascertain whether the intervention programme could reduce the incidence of forearm and hip fractures. Two studies addressed training programmes for middle-aged and old people. First, VOPP participants who were aged 40–70 years and had low forearm bone mineral density (BMD) values were invited to take part in a one-year weight-bearing training study. Thirty of those individuals were included in the investigation. Additional bone mass measurements were performed at the hip and the lumbar spine, and balance and aerobic capacity were also tested. The training programme was performed twice a week (I). In the second study, healthy persons aged 70–75 years were invited to participate in a balance-training study. Fifteen persons joined an exercise group, and another fifteen were controls. The training programme comprised specific balance exercises and was carried out twice a week for nine weeks (II). The association between forearm BMD values and several lifestyle factors was explored in random samples of the population aged 20–72 years (n=880) in a cross-sectional study (III). Another study explored the association between calcaneal stiffness, forearm BMD, and lifestyle factors amongst participants aged 20–79 years (n=956) at the final registration of the VOPP (V). Effects of the VOPP interventions directed at environmental risk factors for falls and the promotion of physical activity were examined in people aged ≥ 65 years (IV). The incidence of forearm and hip fractures was studied amongst middle-aged and elderly individuals in the intervention and the control communities during the study period 1987–2001 (VI). The exercise group (n=15) in the weight-bearing training study showed increases in BMD at the greater trochanter (p&lt;0.01), one-leg stance balance with the eyes closed and coordination tests (p&lt;0.05), and aerobic capacity (p&lt;0.05). No significant difference was found when the groups were compared concerning changes in the different tests during the intervention period (I). In the balance-training study, the exercise group showed post-training improvement in the following tests: standing on the right leg with eyes closed (p&lt;0.01), standing on the right leg (p&lt;0.01) and on the left leg (p&lt;0.05) while turning the head, and walking 30 metres (p&lt;0.01). There were significant differences between the groups in these tests when changes were compared at the post-intervention test (II). Age (p&lt;0.0001) and body mass index (p≤.0001) were associated with forearm BMD in both sexes. Reported moderate physical activity levels in men were positively associated with forearm BMD (p&lt;0.05) (III). In both sexes, reported moderate (p&lt;0.05) and high (women p&lt;0.05 and men p&lt;0.001) physical activity levels were positively associated with calcaneal stiffness. The correlation coefficient between forearm BMD and calcaneal stiffness was 0.58 in women and 0.34 in men (V). Persons aged ≥ 65 years at the follow-up in 1994 reported more use of shoe/cane spikes and moderate physical activity levels compared to controls (IV). There was no change in the general incidence of forearm and hip fractures between the communities for the study period. However, there was a tendency towards decreasing incidence of forearm and trochanteric hip fracture in both sexes during the late intervention period in the intervention community (VI). A community-based intervention programme aimed at reducing the incidence of osteoporotic fractures must be regarded as a long-term project and should preferably be monitored over an extended post-intervention period. / On the day of the public defence the statuses of articles IV and V were Submitted and VI was Manuscript

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Le rôle de la microstructure trabéculaire et corticale dans la résistance osseuse et le risque de fracture est bien documenté mais son déterminisme génétique n’a pas encore été étudié. Pour savoir si la microarchitecture osseuse et le métabolisme osseux ont un déterminisme héréditaire, une étude épidémiologique transversale (étude MODAM) a été menée pour évaluer la ressemblance familiale de la microarchitecture osseuse chez les femmes ménopausées et leurs filles non ménopausées en utilisant la tomodensitométrie quantitative périphérique haute résolution (HR-pQCT). Nous avons constaté que les filles des femmes ayant subi une fracture ont une densité osseuse volumétrique totale (vBMD) plus faible, des corticales amincies, et une altération de la microarchitecture osseuse trabéculaire au niveau du radius distal et du tibia comparativement aux filles dont les mères n’ont pas eu de fracture. Une autre étude épidémiologique transversale (étude MINOS) a été menée pour évaluer la corrélation de la densité minérale osseuse (DMO), de la taille des os, des marqueurs du remodelage osseux (BTM) et des hormones de régulation du remodelage osseux dans des paires de frères et des paires d'hommes non apparentés, appariés pour l'âge, le poids et la taille. Nous avons constaté que la taille des os, la DMO à certains sites du squelette et la plupart des BTM étaient plus fortement corrélés chez les frères comparativement aux hommes non apparentés. Ces données suggèrent un déterminisme héréditaire substantiel des niveaux de BTM chez les hommes. En conclusion, nous développons et confirmons l'importance des facteurs familiaux dans la pathogénie de l'ostéoporose chez les femmes et les hommes / The role of trabecular and cortical microstructure in bone strength and fracture risk is well documented, but its genetic determinism has not yet been studied. To find whether the bone microarchitecture, and bone metabolism have a strong hereditary determinism, a crosssectional epidemiological study (MODAM study) was conducted, investigating the familial resemblance of bone microarchitecture in postmenopausal mothers and their premenopausal daughters using high-resolution peripheral quantitative computed tomography (HR-pQCT). We found that daughters of women with fracture have lower total volumetric bone mineral density (vBMD), thinner cortices, and impaired trabecular microarchitecture at the distal radius and tibia, compared with daughters of women without fracture. Another cross-sectional epidemiological study (MINOS study) was conducted to assess the correlation of bone mineral density (BMD), bone size, bone turnover markers (BTMs) and hormones regulating bone turnover in pairs of brothers and pairs of unrelated men, matched for age, weight and height. We found that bone size, BMD at some skeletal sites and most of the BTM levels correlated more strongly in the brothers than in the unrelated men. These data suggest a substantial hereditary determinism of the BTM levels in men. In conclusion, we expand and confirm the importance of familial factors in the pathogenesis of osteoporosis in both women and men