In vitro osteoclastogenesis in autoimmune diseases – Strengths and pitfalls of a tool for studying pathological bone resorption and other disease characteristics

Osteoclasts play a critical role in bone pathology frequently associated with autoimmune diseases. Studying the etiopathogenesis of these diseases and their clinical manifestations can involve in vitro osteoclastogenesis, an experimental technique that utilizes osteoclast precursors that are relatively easily accessible from peripheral blood or synovial fluid. However, the increasing number of methodical options to study osteoclastogenesis in vitro poses challenges in translating findings to clinical research and practice. This review compares and critically evaluates previous research work based on in vitro differentiation of human osteoclast precursors originating from patients, which aimed to explain autoimmune pathology in rheumatic and enteropathic diseases. The discussion focuses primarily on methodical differences between the studies, including the origin of osteoclast precursors, culture conditions, and methods for identifying osteoclasts and assessing their activity. Additionally, the review examines the clinical significance of the three most commonly used in vitro approaches: induced osteoclastogenesis, spontaneous osteoclastogenesis, and cell co-culture. By analyzing and integrating the gathered information, this review proposes general connections between different studies, even in cases where their results are seemingly contradictory. The derived conclusions and future directions aim to enhance our understanding of a potential and limitations of in vitro osteoclastogenesis and provide a foundation for discussing novel methods (such as osteoclastogenesis dynamic) and standardized approaches (such as spontaneous osteoclastogenesis) for future use in autoimmune disease research.