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Abstract Background  In patients with bone metastases, pain may be absent or moderate at rest, but may be exacerbated by different movements or positions. No study has evaluated separately pain at rest and on movement in patients with bone metastases undergoing treatment with zoledronic acid (ZA). Aim  The aim of this prospective observational study was to evaluate the reduction in intensity of pain at rest and in movement-related pain after treatment with up to six infusions of ZA 4 mg every 28 days in patients with painful bone metastases due to breast or prostate cancer cared for at the Oncological Units and Pain Therapy and Palliative Care Unit of the NCI of Milano. Materials and methods  Pain was assessed by a six-level verbal rating scale (0–5 score) at baseline and on each infusion as well as at follow-up visits (2 weeks after every infusion). The two main endpoints (estimated reduction in pain and movement-related pain) were defined as the difference between the baseline score and the average of all the post-treatment scores for each patient. To allow for the potential confounding effect of analgesic consumption, patients without any increase in analgesic consumption during zoledronic acid treatment were also analyzed as a separate subgroup. Results  Forty-eight patients with breast (34) or prostate cancer (14) were enrolled. At baseline, 100% of the patients had pain on movement, in 65% of them, the intensity ranged from moderate to very severe, in 61% of the patients, the intensity of pain on movement was higher than the intensity of pain at rest (average difference 0.89; 95% CI, 0.5–1.30). The estimated mean intensity reduction of pain at rest and on movement was: (a) 0.62 (95% CI, 0.28–0.98) and 0.79 (95% CI, 0.43–1.14), respectively, during the first 90 days of ZA treatment; (b) 0.59 (95% CI, 0.23–0.96) and 0.86 (95% CI, 0.49–1.23), respectively, during the entire treatment and follow-up period. Analgesic consumption decreased or was stable on average in 31 and 27%, respectively, of available follow-up data. In the 14 patients with decreased or stable analgesic consumption, pain reduction was 0.61 and 1.01, respectively. Conclusions  In this study, at baseline, all the patients with painful bone metastases experience movement-related pain, and during zoledronic acid treatment, a decrease for both pain at rest and on movement was obtained. [ABSTRACT FROM AUTHOR]