 Cancer is the leading cause of death worldwide. Cancer patients die from metastasis at distant locations such as bone. Bone metastasis cause fractures, pain, poor quality of life and poor survival. A cancer primarily affecting the bone marrow in which blood cells are produced is called multiple myeloma. In multiple myeloma, tumor cells secrete abundant amounts of immunoglobulins and either diffusely infiltrate the bone marrow or grow as multiple focal lesions. Eighty percent of patients with multiple myeloma suffer from severe bone destruction since myeloma cells in the bone marrow destroy the surrounding bone tissue. Current pharmacological treatment strategies have not succeeded in either healing bone lesions or regenerating bone tissue even in the absence of signs of active disease. Therefore, novel treatment options are urgently needed to regenerate bone tissue and to reduce fracture risk in patients with multiple myeloma. In healthy individuals, it is known that physical stimuli in form of physical activity increase bone mass and have therefore an anabolic effect. For example, in athletes such as professional tennis players, the playing arm compared to the non-playing arm have a bigger bone mass. So my research question finally is whether and how in patients with multiple myeloma or with the precursor condition monoclonal gamopathy of undetermined significance, physical activity or physical stimuli might affect bone mass in tumor infiltrated bones. To address the research question, we anoculated tumor cells into the tibiae of mice. Tumor cells locally grew for two weeks. After two weeks, one half of the mice received physical stimuli, the other half did not. For physical stimulation, we used a technique which is called axial compressive mechanical loading. This technique, the tumor inoculated tibiae were clamped into a stamp field and cyclic compressive loading was applied for three weeks. We continuously measured bone structural changes through use of micro CT, micro computed tomography in living mice under anesthesia. CTs use X-rays for visualization of bone structural changes. We further monitored local and even distant tumor growth through use of bioluminescence analysis. Bioluminescence is based on the fluorescence of tumor cells, of labelled tumor cells, which are detected by a camera. In a second approach, we used the knowledge gained from our preclinical results and transferred this knowledge to a clinical study with patients with monoclonal gamopathy of undetermined significance. It is known that these patients have compromised bone structures and that they also have an increased fracture risk. We applied whole body vibration exercise to these patients with monoclonal gamopathy. In whole body vibration exercise, patients either stand or sit on a vibration platform. This machine, if patients stand there, transduce energy to muscles which contract and relax alternately. And by that, the underlying skeleton is stimulated. So these two setups, both in animals and in humans, were used to answer the question, how physical stimulation might affect bone structures. Let me just summarize the findings of our mouse study and then comment on the clinical results. Labelled tumor cells in inoculated tibia grow for two weeks. Afterwards, tumor cells heavily disseminated throughout the skeleton of tumor-infiltrated mice. Micro-CT analysis revealed that tumor cells destroyed the inner trabecular as well as the outer cortical part of the bone. Three-dimensional renderings of these micro-CTs even showed that tumor cells caused small holes in the cortex and that the trabecular structures were complete lost. In contrast, in mice which received mechanical stimulation over time, we showed a conserved bone structure and we could even demonstrate that cortical bone formation took place. Interestingly, the local mechanical stimulation even led to a diminished local as well as disseminated tumor growth. We observed similar effects in our clinical study with respect to physical stimulation. Whole body vibration in patients with monoclonal gamopathy led to a highly significant increase of physical performance. Improvement of physical performance has been demonstrated by a reduction in time to rise a chair or to walk a distance in six minutes. So the tests we had done clearly demonstrated that we had an improve in physical performance which is based on improvements in musculoskeletal functions. And these functional improvements are a prerequisite for changes in the underlying bone structures. Accordingly, our patients, our female patients in the study showed an improvement in bone mineral density on basis of whole body vibration over time in the clinical study. So both the animal study as well as the human study clearly demonstrated that physical stimuli in form of physical activity influence bone structures in tumor infiltrated bones. Let me just give you the relevance of our findings both of the preclinical mouse study as well as of the clinical study with patients with monoclonal gamopathy. We provide first time evidence in our mouse model of myeloma bone disease that local physical stimuli are able to work anabolic in two more infiltrated bones. In bones where aggressively growing litically active tumor cells were inoculated. At the same time, we could demonstrate that physical stimuli, local physical stimuli are able to have anti-tumor effects for local as well as disseminated tumor growth. Similarly, our clinical study provided evidence in patients with monoclonal gamopathy that physical stimuli have an improved effect on physical performance as well as bone turnover. This means that we could use physical activity as a non-pharmacological adjuvant approach in patients with cancers with bone involvement. Our studies therefore provide the scientific basis for a targeted use of sports against bone cancer. I give you the outlook for our mouse experiments. We could demonstrate that physical stimuli are both anabolic and have an anti-tumor effect in myeloma bone disease. We are now interested in how physical stimuli might change the tumor microenvironment to transduce these effects. And to answer this open question, we like to set up experiments where we use physical stimulation and afterwards analyze gene expression changes in those cells of the bones called cortical osteocytes, which are influenced both by the tumor as well as by the physical activation. And through these experiments, we try to answer the question how physical stimuli have their effects on bone. In patients, we would like to set up a follow-up study where we analyze in multiple myeloma patients with a more advanced disease, patients who already have lytic lesions in their skeleton, how physical activity might influence bone structure, bone turnover and even bone mineral density. This follow-up study, we will use whole body vibration in combination with even more bone effective treatment, which is called impact training.