Modelling Osteoporosis in Pre-Clinical Research—Challenges, Trends and New Approaches

Abstract

Highlights: What are the main findings? A comprehensive comparative analysis of current approaches to model osteoporosis, including in vivo, in vitro, and in silico systems. Identification of key limitations of current animal models and the emerging potential of advanced human-derived in vitro platforms. What are the implications of the main findings? Advanced in vitro and organ-on-a-chip technologies are useful tools for bridging the translational gap between experimental research and clinical application. Integrating human-based and computational models may accelerate the development of more predictive, mechanism-driven therapeutic strategies. Osteoporosis is a bone disease characterized by low bone mass and changes in bone architecture, often leading to fractures and thereby decreased functional status in affected patients. About 200 million people worldwide suffer from osteoporosis, with women being affected earlier in life and more often than men. Various factors, such as genetic background, comorbidities, alcohol abuse, and medications such as glucocorticoids, are known to contribute to the development of osteoporosis. Due to the changing demographics, osteoporosis is becoming increasingly prevalent, and with this, the rate of fractures is expected to increase in the coming years. To investigate therapeutic options for treatment and to elucidate disease-causing mechanisms, various in vivo and in vitro osteoporosis models have been developed. In vivo models, in particular small animal models, remain the gold standard for osteoporosis research and the most used model to illustrate osteoporosis is the ovariectomized mouse. While in vivo models largely reflect the systemic and biological conditions, the transferability of findings to human patients is low and ethical concerns for laboratory animals must be considered. Thanks to tremendous technological improvements, such as on-a-chip platforms and high-end bioreactor systems, sophisticated in vitro models are of growing interest. These models offer the possibility of using complex cell systems, human cells from single donors, and 3D models, thus bridging the transferability gap, providing a platform for the introduction of personalized precision medicine, and ultimately replacing animal testing. Here, we summarize and discuss recent in vivo, in vitro, and in silico osteoporosis research approaches.