Drug development remains a long and costly process with low success rates in clinical trials. This is even more pronounced in bone diseases that can have various underlying causes and often develop slowly before they can even be diagnosed. On top of that, many cell-based drug screens are performed in 2D environments, whereas evidence suggests that particularly for bone, 3D culture technologies might provide better precision. Within the BoneScreen project, a drug screening platform based on porcine bone material was developed that can visualize the interplay between the bone cells within their native 3D environment into account. We show that we can both identify and follow bone formation and resorption in an ex vivo model system over a duration of 6 weeks qualitatively and quantitatively with non-destructive micro-computed tomography, confirmed by end-point biochemical measurements and histology. Its experimental design is cost-effective and acceptable in terms of animal welfare and in accordance with the 3Rs. Further research is needed to optimize the culture conditions representing both the physiological and the pathological and to proof that the model is predictive of the human situation before it can be commercialized.