The maintenance of the skeleton is tightly coupled with balanced bone formation and resorption processes that are mediated by osteoblasts and osteoclasts, respectively. Loss of this balance results in skeletal pathologies representing some of the most significant public health threats faced by the growing and ageing population. Tissue engineering investigates various health aspects such as drug development, fundamental research and regenerative medicine. State-of-the-art approaches are lacking to mimic one essential functional property of bone: to adapt its 3D morphology according to imposed mechanical loads. As most drugs for skeletal diseases act on this anabolic-catabolic balance, an engineered system serving as a human in vitro model for drug discovery/testing needs to be able to mimic this process. This proposal aims at combining real-time monitoring of mineralized extracellular matrix with bone tissue engineering culture standards in advanced bioreactors and will design a reliable 3D in vitro model system to mimic load induced remodeling of tissue-engineered human bone. The following particulars will be systematically addressed: i) Establishment of a co-culture of human bone-forming cells and human bone resorbing cells capable of mimicking bone remodeling; ii) Real-time monitoring platform in 3D in order to take the temporo-spatial development of the tissue into account and to allow specific adapted and controlled interventions depending on the actual environmental situation; iii) Quantitative simulation of morphological bone adaptation induced by mechanical load. The proposed research activity will have important implications in fields ranging from pharmacology and biotechnology to biomechanics and medicine. It will result in a ground-breaking platform that could be applied to screen initial bone drug effects and will improve our fundamental understanding of structure-function relationships in normal and diseased bone conditions.