Histologic bone analysis is the only method that provides reliable diagnostic information; it reveals the details of skeleton structural alterations and is, moreover, the gold standard to validate other non-invasive histologic methods. Its diagnostic value is unquestionable but its invasive nature limits its application.

Until 1960 bone samples were previously decalcified, making it impossible to differentiate between osteoid and mineralized bone. A significant advance in this field was the introduction of processing techniques without decalcification and the use of specific stains making it possible to differentiate mineralized from non-mineralized bone.