A clinical follow-up method was developed to investigate the behavior of a massive amount of bioactive glass S53P4 (BG) clinically used in frontal sinus obliteration. Two sizes of granules (0.63-0.8 mm or 0.8-1.0 mm) in 16 separate BG amounts, weight 25 g, were tested both in simulated body fluid (SBF) and in a buffer containing tris-hydroxymethyl aminomethane citric acid (TRIS-c.a) in standard conditions. The dissolution of silicon (Si) and phosphate (P) was detected with direct current plasma atom emission spectroscopy (DCP-AES) monthly up to 6 months. The BG masses were scanned both wet in the solutions and dried by computer tomography (CT), and the scans were analyzed by Region of Interest (ROI) technique. Calcium phosphate (CaP)- and silica (Si)-gel-layers were studied by scanning electron microscopy (SEM) at 1, 3, and 6 months. Cumulative loss of Si and P was stronger in TRIS-c.a than in SBF (p < 0.0001), and it was higher with smaller than with larger granules in both solutions (p < 0.0001). This was shown correspondingly by the decrease of Hounsfield units (HUs) in ROI analysis (p < 0.0001). The level of HUs was lower with dried than with wet BG (p < 0.0001). The results were compared for clinical ROI analysis of patients with obliterated frontal sinuses up to 48 months and they were parallel. The follow-up method seems to indirectly reveal the behavior of BG and the healing process in the obliterated cavity.