Skin problems and Osteoporosis may be related via Vitamin D, Microbiota, and Epigenetics
Skin Disorders and Osteoporosis: Unraveling the Interplay Between Vitamin D, Microbiota, and Epigenetics Within the Skin-Bone Axis
Ini. J. Mol. Sci. 2025, 26, 179. https://doi.org/10.3390/ ijms26010179
Vincenzo Papa 1,+, Federica Li Pomi 2,+ , Paola Lucia Minciullo 2'*, Francesco Borgia 3 and Sebastiano Gangemi1
Growing scientific evidence suggests a strong interconnection between inflammatory skin diseases and osteoporosis (OP), a systemic condition characterized by decreased bone density and structural fragility. These conditions seem to share common pathophysiological mechanisms, including immune dysregulation, chronic inflammation, and vitamin D deficiency, which play a crucial role in both skin and bone health. Additionally, the roles of gut microbiota (GM) and epigenetic regulation via microRNAs (miRNAs) emerge as key elements influencing the progression of both conditions. This review aims to examine the skin-bone axis, exploring how factors such as vitamin D, GM, and miRNAs interact in a subtle pathophysiological interplay driving skin inflammation and immune-metabolic bone alterations. Recent research suggests that combined therapeutic approaches—including vitamin D supplementation, targeted microbiota interventions, and miRNA-based therapies— could be promising strategies for managing comorbid inflammatory skin diseases and OP. This perspective highlights the need for multidisciplinary approaches in the clinical management of conditions related to the skin-bone axis.
Conclusions and Perspectives (start of)
From the discussion so far, it is clear that skin and bone should be considered distinct organs only from an anatomical perspective. Functionally, however, they share immunoendocrine mechanisms that act as a balancing point between health and disease in both organs. Clinically, this bidirectional immunoendocrine communication is most evident in the well-documented association between OP (which can be regarded as an inflammatory condition) and major chronic autoimmune/inflammatory diseases or skin fragility disorders. Therefore, within the context of the recognized skin-bone axis, the skin reflects the health status of the bone and, conversely, the bone mirrors the health status of the skin. The etiopathogenetic bidirectionality of this axis is governed by pro-inflammatory pathophysiological mechanisms involving various cytomolecular players, including skin-derived cytokines and bone-derived cytokines (osteokines). In such a bidirectional framework, aging and the associated low-grade chronic inflammation (inflammaging) are well-established influencing factors. Additionally, an emerging etiopathogenetic role can be attributed to the pathophysiological interplay involving gut dysbiosis, vitamin D deficiency, and miRNA dysregulation, which can be considered the three common denominators of both skin and bone inflammatory responses. This interplay affects two crucial physiological mechanisms: redox balance and immune homeostasis. The resulting imbalance leads to increased ROS production and organ-specific inflammation, which reciprocally influence each other. The influence of the discussed pathophysiological interplay on the dysregulation of two key biological mechanisms becomes particularly evident in vitiligo. Here, vitamin D deficiency, through the downregulation of antioxidant pathways, leads to increased ROS production. This process is further supported by a specific state of gut dysbiosis, characterized by reduced Bacteroidetes and Lachnospiraceae, and by the upregulation of specific miRNAs (miR-25, miR ...
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