The influence of the substitution of calcium oxide for sodium oxide in the composition of silica-based glasses on the in vitro bioactivity is presented. Valuable information on the active Si-O groups present in the glasses is obtained by Fourier Transform Raman and Infrared spectroscopies. In vitro test analysis by Scanning Electron Microscopy and Energy Dispersive X-ray Analysis show a correlation between the network disruption induced by the modifier type and the bioactive process. It is demonstrated that glasses with high SiO2 content can be bioactive depending on the alkali/alkali-earth modifiers ratio included into the vitreous silica network.