Drug development remains a long and costly process with low success rates in clinical trials. While a majority of cell-based compound screenings are still based on 2D experiments, compelling evidence suggests that 3D culture technologies will accommodate for a better precision in drug discovery. On the other hand, such screening cultures are particularly challenging in terms of 3D visualization. In the BoneScreen project, we propose to develop a high content screening (HCS) platform capable of identifying drugs that alter the reaction of bone cells in terms of bone formation and/or resorption (called bone remodeling). Abnormal bone remodeling is the primary cause of bone diseases such as osteoporosis. Limitations in the development of effective therapeutics for bone remodeling disorders are that the interplay between the bone cells has been ignored, as well as their 3D environment. The micro-computed tomography based monitoring technology of the BoneScreen project is combined with an ex vivo 3D osteochondral system preserving the viability and interactions of tissue-specific cells and their environment. Drug effects are validated in this ex vivo platform by comparison with known drug effects on bone. This system will allow reducing the number of animal experiments needed in drug discovery for bone diseases, as promising leads can first be screened ex vivo before being investigated in vivo. Its experimental design is cost-effective and acceptable in terms of animal welfare and in accordance with the 3Rs. We aim to assess and demonstrate its commercial value to the pharmaceutical industry by building a strong knowledge transfer strategy and by further exploring the platform for potential other applications. In conclusion, the BoneScreen platform has a great fundamental and commercial potential in various fields such as drug discovery for bone diseases.