abstract: The gold standard for bone measurement is DXA (dual energy X-ray absorptiometry). Typically, to observe changes in bone by DXA, a minimum of a 4-month intervention is required. Serum osteocalcin (OST) (a bone formation marker) and quantitative ultrasound (QUS) of the calcaneus can be used as indicators of bone change but the sensitivity and time course of these indices to short term interventions are unknown. The purpose of this study was twofold: to compare monthly changes in OST and QUS in response to jump training and to evaluate the relationship between DXA, OST and QUS. Young women with QUS t-scores less than 1.0 were randomized into a jump training (J) (n=16) or control (C) (n=16). J consisted of a progressive routine of 1 and 2-footed jumping performed 3 days per week for 4 months. Body composition, QUS and OST were measured at baseline, and monthly for 4 months. DXA and 24-hour dietary recalls were completed at baseline and 4 months. Low attrition rate (12.5%) and high compliance (98%) with the exercise intervention was recorded. No significant correlations between QUS and OST existed. No significant differences were observed between groups at baseline in body composition or bone variables. Monthly increases in OST were observed but there were no significant differences over time between groups in any bone variables. OST and QUS may be indicative of short term bone changes but these variables were not specifically sensitive to the jumping intervention in this population of women. / Dissertation/Thesis / Ph.D. Physical Activity, Nutrition and Wellness 2011

Osteoporose und gestörte Heilungsverläufe von Knochenbrüchen verursachen immer noch beachtliche klinische Komplikationen. Ein vielversprechender Ansatz für die nichtinvasive und nichtionisierende Abschätzung des Frakturrisikos und der Bildgebung von Frakturheilung ist quantitativer Ultraschall (QUS). Dennoch liegt die derzeitige Akzeptanz für die Knochenqualitätsabschätzung noch weit hinter herkömmlichen röntgenbasierten Anwendungen. Es wurden akustische Mikroskopie und Synchrotronstrahlen-Mikrotomographie für die Anatomie und altersabhängige Erfassung von strukturellen und elastischen Variationen auf der mikroskopischen Ebene von humanen Femora verwendet. Die gewonnenen Daten dienten als Grundlage für die Erstellung mikromechanischer Modelle von Knochen für numerische Simulationen der Schallausbreitung im humanen Femurhals. Dabei wurde der Aufbau eines US-basierten Femur-Scanners in transversaler Transmission (TT) nachempfunden. Im letzten Abschnitt der Arbeit wurde QUS in TT in in vitro Experimenten am Rattenfrakturmodell auf eine Anwendung für die Bildgebung der Frakturheilung getestet. Die Studien konnten zeigen, dass ein Großteil der adaptiven Fähigkeiten von Knochen auf mikroskopischer Ebene auf eine Kombination von extrazellulärer Matrixelastizität und Gewebeporosität zurückzuführen ist. Die Simulationen des zweiten Teils konnten die Existenz von geführten Wellen im humanen Femurhals bestätigen. Die sensitive Abhängigkeit von US-parametern von frakturrelevanten Knocheneigenschaften zeigt das hohe Potential von QUS für die Frakturrisikoabschätzung. Der zweite Teil der Arbeit konnte erfolgreich die Möglichkeit von QUS in TT zur Diskriminierung von zeitigen Heilungsstadien demonstrieren. Zusammenfassend bestätigt die Studie das hohe Potential von QUS für die Frakturrisikoabschätzung und die Bildgebung der Frakturheilung. / Osteoporosis and impaired bone healing are of high relevance. A promising non-invasive, non-ionizing candidate for fracture risk prediction and monitoring fracture healing is quantitative ultrasound (QUS). However, the acceptance of QUS for bone quality assessment is still not comparable to X-ray based methods. Scanning acoustic microscopy (SAM) and Synchrotron Radiation micro-computer tomography (SRµCT) has been used to investigate anatomical and age dependent variations of micro elastic, structural and mineralization parameters at the tissue level of human femoral bone. Femoral neck models were created based on these data for numerical sound propagation simulations emulating a transverse transmission (TT) setup of an in vivo QUS prototype. In the last part of the project the TT approach has been tested in ex vivo experiments in a rat healing model. The power of QUS, to discriminate two early healing stages has been compared to µCT measurements at the same specimens. It was found that the major contributor to bone adaptation is related to a combination of extracellular matrix elasticity and tissue porosity. It is hypothesized that these parameters are likely to have a considerable impact on the reliability of in silico models. The simulations of the second part confirmed the existence of guided wave propagation in the cortical shell and a high dependency of US parameters on fracture relevant bone properties. The results demonstrate the high potential for bone fracture risk prediction at the femoral neck using QUS. Finally, it was successfully demonstrated that early healing stage discrimination of QUS in TT was superior compared to µCT. In summary these investigations not only show the importance for a precise estimation of micro mechanical properties for numerical modelling but also demonstrate the feasibility and high potential of QUS for bone quality assessment and monitoring of fracture healing.