The prevalence of bone-related disorders, such as osteoarthritis (OA), osteoporosis (OP), bone abnormalities, and lumbar disc herniation, has experienced a significant surge due to the global phenomenon of aging [1], [2], [3], [4]. These diseases have a significant impact on individuals' well-being and overall quality of life, while also placing a substantial financial strain on both families and society as a whole [5], [6], [7]. The global prevalence of OA is estimated to be over 250 million individuals, with projections indicating a further rise in incidence [8]. According to statistics, the expenses associated with treating osteoarthritis in certain wealthy nations can amount to 1–2.5 percent of the gross domestic product [9]. At present, the primary modalities employed in the management of OA encompass pharmaceutical therapy and surgical intervention [10], [11]. Nevertheless, analgesics and anti-inflammatory medications frequently employed in pharmacological interventions can solely alleviate pain and not provide a complete cure. Furthermore, while surgery is a viable treatment for severe osteoarthritis, it often comes with several complications. Currently, there is no efficacious remedy available to reverse the advancement of OA [12], [13], [14], [15]. The global prevalence of OP exceeds 200 million individuals [16]. The annual cost of fractures associated with OP is estimated to be over $1.79 billion in the United States and £4 billion in the United Kingdom [17]. Furthermore, 21–30 % of hip fractures induced by OP lead to the patient's demise within a span of 1 year [18]. Regrettably, the treatment of OP typically necessitates a substantial duration, often spanning a lifetime, and is accompanied by numerous adverse consequences [19], [20]. Approximately 20,000 new cases of osteonecrosis are diagnosed annually in the United States, resulting in a cumulative total of 300,000 to 600,000 people affected by the condition [21]. Japan has reported approximately 12,000–24,000 new cases of osteonecrosis in recent years. Korea estimates the average annual incidence of new cases to be 14,103 [22]. According to epidemiological research in China, the total number of patients with non-traumatic osteonecrosis is estimated at 8.12 million [23], [24]. The incidence of osteosarcoma in the general population is 2–3/million/year, accounting for 15 % of all extracranial solid tumours in this age range [25], [26]. Both autologous and allogeneic bone grafts have been extensively utilised to cure bone abnormalities; nevertheless, there are still several drawbacks to these approaches, including immunological rejection, restricted availability of autologous bone, and inflammation [27], [28], [29], [30]. The current management of orthopaedic illnesses relies on surgical intervention, radiation, and chemotherapy. However, these approaches frequently result in unfavourable prognosis, therapeutic ineffectiveness, and frequent recurrence, significantly impacting patients' quality of life and perhaps leading to mortality [31], [32]. Stem cell therapy has emerged as a leading approach in bone regenerative medicine in recent years [33], [34]. However, its chemical mechanism is yet unknown, and it has drawbacks such as a high cost and a limited donor base. Thus, different and unique therapeutic techniques are urgently required to satisfy the clinical needs of bone diseases. In recent decades, cell-free therapy has emerged as one of the most promising techniques for improving the current status quo [35]. Therefore, we recommend the use of exosomes generated from various cells as a therapeutic technique for illness treatment through ferroptosis regulation.

Exosomes, which have a diameter ranging from 30 to 150 nm, are minute intercellular vesicles responsible for the transportation of proteins, nucleic acids, bioactive lipids, and various other bioactive compounds across cellular boundaries [36]. Cytokinesis is the mechanism by which they are released from cells into the extracellular microenvironment. Upon interaction with receptor cells, these molecules initiate molecular release or signal transduction cascades, which eventually result in alterations in cellular activity or function [37]. Currently, there is significant evidence that MSCs exert their biological effects through the production of paracrine mediators, specifically exosomes [38]. Exosomes, being a significant conduit for intercellular communication, assume a pivotal function in the diagnosis and treatment of diseases through their intricate regulation of inflammatory responses, angiogenesis, and cytoprotection subsequent to injury [39], [40].

Ferroptosis represents a distinctive form of cell death intricately tied to iron dependency, setting it apart distinctly from apoptosis, necrosis, and autophagy [41]. The crux of ferroptosis lies in the depletion of glutathione, the diminution of glutathione peroxidase (GPX4) activity, the incapacity of lipid oxides to undergo metabolism via the GPX4-catalyzed glutathione reductase reaction, and the ensuing lipid oxidation facilitated by divalent iron ions, resulting in the generation of reactive oxygen species, thereby precipitating ferroptotic cascades [42]. Related research has demonstrated that ferroptosis plays a significant role in orthopaedic illnesses [43], [44], [45], [46], [47]. Considering the strong correlation between ferroptosis and the initiation and advancement of numerous diseases, it is imperative to devise novel approaches to combat ferroptosis.

Recently, the mechanisms underlying the role of exosomes and ferroptosis in disease have become progressively clearer, and exosomes, as intercellular information transfer pathways, have been shown to be important in the regulation of ferroptosis processes. The study of engineered exosomes that regulate ferroptosis can address the shortcomings of adverse reactions, drug resistance, and complications that occur in traditional therapeutic approaches, and is gradually becoming a research hotspot with potential clinical applications. Some studies have confirmed the involvement of exosomes in disease progression by regulating ferroptosis [48]. This review will focus on the application of ferroptosis as a target of exosome regulation in related diseases. Notably, exosome-regulated ferroptosis is a “double-edged sword,” suggesting the importance of exosomes in regulating disease progression by rationally inducing or inhibiting ferroptosis.