The most frequently used instruments for health-related quality of life (HRQL) in patients with osteoporosis are the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) and the Osteoporosis Assessment Questionnaire (OPAQ 2.0 and OPAQ SV). Since HRQL- and International Classification of Functioning, Disability and Health (ICF)-based approaches have both strengths and weaknesses, it is expected that they will be used simultaneously in clinical practice and research. Therefore, we investigated the relationship between osteoporosis-targeted instruments and the ICF. All three selected instruments cover body functions, including pain in back and emotional functions. Sleep functions and energy are represented in the QUALEFFO-41 and OPAQ 2.0 but not in the OPAQ SV. Body structures and environmental factors are covered only by the OPAQ 2.0 and OPAQ SV. The ICF provides an excellent framework when comparing the content of osteoporosis-targeted HRQL instruments and may be useful when selecting health status instruments for clinical studies.