Osteoid Definition and Bone Formation

Bone formation begins with the establishment of a tissue called osteoid, traditionally described as unmineralized. Despite extensive research on bone, this primary tissue remains surprisingly understudied, as reflected by the very limited number of reviews dedicated to it. Current understanding largely relies on data from diverse experimental models, ranging from human bone to calcified chicken tendon, and spanning different stages of development (from embryo to adult), although bone structure and formation vary across these systems. At the crossroads of multiple disciplines, osteoid description also depends on the techniques used in a research field, such as histological stains or transmission electron microscopy, which probe very different length scales. Over time, findings have been combined and extrapolated, often without direct evidence in humans. This review emphasizes the importance of osteoid by critically evaluating the existing literature. It aims to integrate current knowledge of processes occurring in osteoid, from collagen fibrillogenesis to the mineralization front, and to provide a renewed perspective on a tissue whose structure and composition are crucial for establishing the scaffold for mature healthy bone. Revisiting osteoid tissue characteristics should deepen our understanding and inspire new approaches to bone diagnosis.