- Osteoid deposition
Osteoblasts lay down a collagen-I–rich matrix with non-collagenous proteins (e.g., osteocalcin, bone sialoprotein, DMP1). This forms an osteoid seam (typically ~10–20 µm thick in healthy bone). - Priming the front
Osteoblasts increase alkaline phosphatase, lower pyrophosphate (an inhibitor), and concentrate Ca²⁺ and PO₄³⁻ near the osteoid-bone boundary. This creates a narrow mineralization front. - Nucleation
Initial hydroxyapatite crystals nucleate on and within collagen fibrils (gap zones) aided by nucleators like bone sialoprotein; in early/woven settings, matrix vesicles can seed nodules that then fuse with the front. - Propagation (primary mineralization)
The front moves into the osteoid, rapidly raising mineral content to ~60–70% of mature levels over days–weeks. Histologically, the osteoid’s pale eosinophilia gives way to darker, more basophilic mineralized matrix. - Maturation (secondary mineralization)
Over weeks–months, crystal size/packing and mineral-to-matrix ratio continue to increase, stiffening the tissue.
