The purpose of this study was to evaluate the efficacy of calcitonin on beta-endorphin levels in female patients experiencing back pain associated with postmenopausal osteoporosis. The secondary purpose was to assess the pain and quality of life in these patients. There were 30 patients with a mean age of 58.2 +/- 5.4 years in the treatment group and 26 patients with a mean age of 58.8 +/- 5.2 years in the placebo group in this randomized, placebo-controlled study. The patients subcutaneously received 100 IU salmon calcitonin or placebo injections and 1,000 mg elementary calcium for 2 weeks. Baseline plasma beta-endorphin levels were measured and repeated after 2 weeks. Patients' pain and quality of life (QOL) were evaluated by using the Visual Analogue Scale, Modified Face Scale, Beck Depression Index, and Nottingham Health Profile. Patients' global assessment of disease activity was also performed at baseline and at the end of the first and second week. We found that plasma beta-endorphin levels in the treatment group were significantly higher than the placebo group at the end of the second week (p < 0.001). Although pain and QOL scores were improved at the end of the second week in both groups (p < 0.05), the improvement in the treatment group was more significant when compared with the placebo group (p < 0.05). Therefore, calcitonin is an analgesic agent, as it increases the plasma beta-endorphin levels in patients with postmenopausal osteoporosis, which consequently improves QOL.