“…Mentioning only the most important ones, they comprise wide (Engfeldt et al, 1985) and small (Fratzl et al, 1991) angle X-ray diffraction and synchrotron radiation (Ascenzi et al, 1985); selected area electron diffraction (shown in Figure 2, inset; Landis and Glimcher 1978;Arnold et al, 1999); neutron diffraction (Wenk and Heidelbach 1999;Girardin et al, 2000); electron spin resonance spectrometry (Ostrowski et al, 1972;Roufosse et al, 1976;Ascenzi et al, 1977); energy dispersive X-ray elemental analysis, otherwise known as electron-probe analysis (Lewinson and Silbermann 1990); energyfiltering electron microscopy (Egerton 2003;Leapman 2003); infrared spectroscopy (Paschalis et al 1996;Pleshko et al, 1991); and atomic force microscopy (Reich et al, 2001;Santos and Castanho 2004), besides other biophysical techniques. Taken together, these methods have produced an impressive corpus of data which, together with those obtained using histochemical (Brighton and Hunt 1976;Appleton and Morris 1979;Morris and Appleton 1980;Lewinson and Silbermann 1990) and autoradiographic (Lacroix 1960;Nagai and Frank 1974) procedures that aim to determine the movements of calcium and phosphate ions within, and their binding to, the organic matrix, have contributed a great deal to knowledge of the physiopathology of bone and other calcified tissues. The fine structure and composition of the earliest inorganic particles are, however, still uncertain and so far even the availability of techniques as sophisticated as these has failed to produce a definitive explanation of the way inorganic substance is actually deposited in the matrix.…”