The aim of this study was radiographically to monitor the effect of disodium pamidronate on metastatic bone disease, using image-processing techniques. Eighteen patients with osteolytic metastases from breast cancer received an intravenous infusion of 180 mg disodium pamidronate every 4 weeks for a period of 6 months. The first session of intravenous infusions was given concurrently with external beam radiotherapy with a 6 MV linear accelerator (total dose 30 Gy in 10 fractions). Radiographs of osteolytic lesions were obtained at every session of the treatment, retaining the same settings for each modality. The analysis of the attributes of the images was based on measuring the first-order statistics of the gray-level histogram in terms of mean value (MVGLH) and energy (EGLH). The measurements showed significant differences for MVGLH and EGLH values (p < 0.05, Wilcoxon test). Analytically, there was an 11.08% (95% CI = 10.21, 11.93) mean reduction of EGLH and an 11.63% (95% CI = 10.96, 12.29) mean increase of MVGLH of the x-ray images, before and after the combined treatment protocol. The changes in the image-processing indices were also highly correlated with the reduction of the patient's pain score. These findings indicate an important increase in bone mass and bone formation, which the radiologists found difficult to identify visually.