Pathogenesis
Normal enamel formation (amelogenesis) involves: secretory stage (enamel matrix protein deposition) followed by the maturation stage where proteins are enzymatically removed and mineral content rises to 96%.
Fluoride at toxic levels inhibits matrix metalloproteinases (MMP-20 in secretory stage) and kallikrein-4 (KLK4 in maturation stage) — the enzymes responsible for degrading and removing amelogenin matrix proteins.
Retained matrix proteins prevent proper mineral crystal growth and packing, resulting in a hypomineralized, porous enamel subsurface that is softer and more opaque than normal.
The surface zone is relatively more mineralized (maintaining initial surface deposit), while the subsurface remains porous — explaining the characteristic whitish opacity (light scattering from pores) that, when combined with secondary extrinsic staining, appears brown.