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Trauma, osteoporosis (OP), degenerative joint disorders, spinal pathologies, and bone tumors impose a profound burden on patients' health and global healthcare. Conventional anatomical imaging modalities rely heavily on macroscopic structural alterations, which are often observed in a late stage of the disease. These limitations hinder early diagnosis and the timely assessment of therapeutic response. Over the past decades, molecular imaging probes have become powerful tools in clinical practice for the noninvasive visualization of biological and pathophysiological processes at the cellular and molecular levels. This is important for deepening understanding of the intrinsic pathogenesis of the corresponding disease, which can facilitate early diagnosis and treatment. This review evaluates the current status of targeted molecular imaging probes for skeletal diseases. On the basis of the clinical location and disease, we divide the molecular probes for bone diseases into five types: bone trauma and the dynamic repair process, OP, joint diseases, spinal disorders, and bone oncology. In addition, we discuss the frontiers of probe development, including the design of multimodal imaging platforms, the paradigm shift of bone‐targeted therapy, and the integration of artificial intelligence (AI) in accelerating probe discovery. The next generation of clinical probes, combining basic radiochemistry and clinical radiology, has great potential and can provide a reference for future orthopedic precision medicine.

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