BACKGROUND AND AIMS: Osteoporotic fractures are a major public health problem notably affecting quality of life. The observational, multicenter study ICARO was designed to evaluate inadequate clinical response to antiresorptive drugs. The aim of the present study was to evaluate the impact of the clinical response to treatment on the health-related quality of life in women with postmenopausal osteoporosis. METHODS: 880 osteoporotic women (mean age 68.0+/-8 years; range 53-79) in treatment with antiresorptive drugs for at least one year were analyzed. All subjects had at least 50% compliance to treatment (i.e., patients took >50% of prescribed doses). The "inadequate clinical response" (ICR), as opposed to "adequate clinical response" (ACR), was defined as the Xrays revealing evident new vertebral or non-vertebral fragility fractures at least 6 months after initiation of antiresorptive therapy. The QUALEFFO- 41 questionnaire was used to evaluate changes in quality of life prospectively. RESULTS: 220 subjects (25%) had an ICR. Non-responders had a higher incidence of multiple vertebral fractures compared with responders. The quality of life data in the study subjects showed a significantly increased score (indicative of lower quality of life) in the total mean score (37.89+/-16.7 vs 45.84+/-18.2, p