Abstract
Decades of research have revealed the profound impact of diabetes on skeletal health, yet the biological basis of diabetic bone fragility remains incompletely understood, and no existing in vitro or animal model has faithfully recapitulated these disease phenotypes. Organoid technologies are emerging as powerful tools for investigating human biology, modeling disease, and developing novel therapies. While organoids for many tissue types have been developed and continue to advance rapidly due to a growing regulatory shift toward human-relevant in vitro models, bone organoids remain underrepresented, with only a few models described to date. Bone organoids can be generated using cell-based self-assembly or scaffold-based guided approaches, each capable of reconstructing key features of native bone, including its multicellular composition, coordinated remodeling processes, and hierarchical extracellular matrix organization. In this review, we examine progress toward bone organoid development within the broader landscape of soft-tissue organoid innovation and then use diabetes-associated skeletal disorders as a representative case study to highlight the unmet needs and illustrate how next-generation bone organoids could advance the modeling and management of these complex diseases.