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The present work focuses on the application of time-of-flight secondary ion mass spectrometry (ToF-SIMS) in osteoporotic bone research. In order to demonstrate the benefit, the authors present concrete application examples of ToF-SIMS in three different areas of bone research. ToF-SIMS as a mass spectrometric imaging technique allows simultaneous visualization of mineralized and nonmineralized bone tissue as well as implanted biomaterials and bone implant interphases. In the first example, the authors show that it is possible to study the incorporation and distribution of different components released from bone filler materials into bone with a single mass spectrometric measurement. This not only enables imaging of nonstained bone cross sections but also provides further insights beyond histologically obtained information. Furthermore, they successfully identified several mass fragments as markers for newly formed cartilage tissue and growth joint in bone. Different modes of ToF-SIMS as well as different SIMS instruments (IONTOF's TOF.SIMS 5 and M6 Hybrid SIMS, Ionoptika's J105) were used to identify these mass signals and highlight the high versatility of this method. In the third part, bone structure of cortical rat bone was investigated from bone sections embedded in technovit (polymethyl methacrylate, PMMA) and compared to cryosections. In cortical bone, they were able to image different morphological features, e.g., concentric arrangement of collagen fibers in so-called osteons as well as Haversian canals and osteocytes. In summary, the study provides examples of application and shows the strength of ToF-SIMS as a promising analytical method in the field of osteoporotic bone research.