Every year, millions of people worldwide suffer from bone tissue damage caused by bone trauma and surgical operations, as well as diseases such as osteoporosis, osteoarthritis, osteomyelitis, and periodontitis. Bone defect repair is one of the major challenges in the field of regenerative medicine. Although bone grafts are the gold standard for treating bone defects, factors such as donor sources and immune responses limit their application. Functionalized nanomaterials have become an effective means of treating bone diseases due to their good biocompatibility and osteoinductivity, anti-inflammatory, and antibacterial properties. Metal–organic frameworks (MOFs) are porous coordination polymers composed of metal ions and organic ligands, featuring unique physical properties, including a high surface area–volume ratio and porosity. In regenerative medicine, MOFs function as the functions of drug carriers, metal ion donors, nanozymes, and photosensitizers. When combined with other functional materials, they regulate cellular reactive oxygen species, macrophage phenotypic transformation, bone resorption, osteogenesis, and mineralization, providing a new paradigm for bone tissue engineering. This study reviews the classification of functionalized MOF composites in biomedicine and the application of their synthesis techniques in bone diseases. The unique in vivo and in vitro applications of MOFs in bone diseases, including osteoarthritis, osteoporosis, bone tumors, osteomyelitis, and periodontitis, are explored. Their properties include excellent drug loading and sustained release abilities, high antibacterial activity, and bone induction abilities. This review enables readers to better understand the cutting-edge progress of MOFs in bone regeneration applications, which is crucial for the design of and functional research on MOF-related nanomaterials.
