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To address this, a live mitochondrial delivery system composed of CXCR4\u2010engineered macrophages loaded with nanozyme\u2010functionalized mitochondria (CM\u2010MTBM). This system integrates bone\u2010targeted migration, reactive oxygen species scavenging, and communication\u2010mediated mitochondrial transfer. CM\u2010MTBM restores mitochondrial respiration, enhances osteogenic differentiation, and alleviates oxidative apoptosis in BMSCs, thereby promoting metabolic recovery and redox balance. In osteoporotic mice, CM\u2010MTBM treatment markedly improved the trabecular bone microarchitecture and promoted osteogenic repair. Single\u2010cell transcriptomic analysis further revealed the enrichment of osteogenic BMSC subpopulations and functional reprogramming of the bone marrow immune\u2013metabolic microenvironment. Mechanistically, CM\u2010MTBM activated mitochondrial oxidative metabolism while suppressing inflammation and senescence\u2010associated signaling, achieving coordinated metabolic and osteogenic activation. Collectively, this work established a communication\u2010driven mitochondrial transfer paradigm that reframes mitochondrial therapy from passive structural supplementation to communication\u2010driven metabolic reprogramming, establishing a conceptual and technological framework for precision treatment of metabolic bone disorders.<\/jats:p>","DOI":"10.1002\/adma.202521645","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T09:07:13Z","timestamp":1770455233000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Intercellular Communication\u2010Driven Mitochondrial Transfer via CXCR4\u2010Engineered Macrophages Reprograms Bone Marrow Metabolism for Osteoporosis Therapy"],"prefix":"10.1002","volume":"38","author":[{"given":"Di","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine the Second Affiliated Hospital Jiangxi Medical College Nanchang University  Nanchang P. 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