Skin problems and Osteoporosis may be related via Vitamin D, Microbiota, and Epigenetics - Dec 2024

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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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3 of the 9,330 items containing skin osteoporosis microbiome "vitamin D" as of Jan 2025

Google Scholar

• A view on the skin–bone axis: unraveling similarities and potential of crosstalk - March 2024 FREE PDF
• Gut Microbiome and Osteoporosis - 2020 Mar 9 FREE PDF
• The Interplay between Immune System and Microbiota in Osteoporosis - Feb 2020 FREE PDF
• The Association between Vitamin D and Gut Microbiota: A Systematic Review of Human Studies - Sept 2021 FREE PDF

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VitaminDWiki – Overview Osteoporosis and vitamin D contains

• FACT: Bones need Calcium (this has been known for a very long time)
• FACT: Vitamin D improves Calcium bioavailability (3X ?)
• FACT: Should not take > 750 mg of Calcium if taking lots of vitamin D (Calcium becomes too bio-available)
• FACT: Adding vitamin D via Sun, UV, or supplements increased vitamin D in the blood
• FACT: Vitamin D supplements are very low cost
• FACT: Many trials, studies. reviews, and meta-analysis agree: adding vitamin D reduces osteoporosis
• FACT: Toxic level of vitamin D is about 4X higher than the amount needed to reduce osteoporosis
• FACT: Co-factors help build bones.
• FACT: Vitamin D Receptor can restrict Vitamin D from getting to many tissues, such as bones
• It appears that to TREAT Osteoporosis:
•        Calcium OR vitamin D is ok
•        Calcium + vitamin D is good
•        Calcium + vitamin D + other co-factors is great
•        Low-cost Vitamin D Receptor activators sometimes may be helpful
• CONCLUSION: To PREVENT many diseases, including Osteoporosis, as well as TREAT Osteoporosis
• Category Osteoporosis has 223 items
• Category Bone Health has 315 items

Note: Osteoporosis causes bones to become fragile and prone to fracture
  Osteoarthritis is a disease where damage occurs to the joints at the end of the bones

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VitaminDWiki – Osteoporosis category contains

• 223 items in category - see also Overview Osteoporosis and vitamin D
• Overview Fractures and vitamin D
• Bone - Health 315 items
• VitaminDWiki pages with BONE MINERAL DENSITY or BMD in title 29+ pages
• Search VitaminDWiki for OSTEOPENIA 1740 items as of July 2020
• 13 articles are in both Osteroporosis and Vitamin D Receptor categories
• 10 articles are in both Osteroporosis and Meta-analysis categories
• 20X increase in vitamin D sold and 36 percent decrease in osteoporosis business in Australia – Nov 2013

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VitaminDWiki - Skin category contains

123 items below    see also Overview Skin and vitamin D    Psoriasis    Acne   Atopic Dermatitis and Eczema   Chronic Hives
Cancer - Skin category listing has 121 items

Overview Dark Skin and Vitamin D
Overview Suntan, melanoma and vitamin D
Burns, ulcers, and wounds healed by Vitamin D - many studies
Vitiligo (spotty skin) and Vitamin D, UVB - many studies
Warts removed by vitamin D injection - many studies
Skin Aging and Vitamin D - many studies
Vitamin D benefits your skin in 7 ways

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VitaminDwiki – Microbiome contains

Some of the 44 Microbiome articles

• Nutrients, Microbiome, and Chronic Diseases - April 2023
• Fecal transplants - many studies
• Healthy microbiota might reduce COVID-19 – several studies
• Poor absorption of Vitamin D is strongly related to type of gut bacteria – Dec 2020
• Vitamin D and the Host-Gut Microbiome: A Brief Overview– June 2020
• Parkinson's Disease and gut microbiome - several studies
• Vitamin D levels change Gut Microbiota – 25 study review Sept 2021
• Gut Microbiota: improved by Vitamin D – narrative review – July 2021
• Gut microbiome massively changed by weekly vitamin D – July 2015
• Also: Google Scholar on Microbiome includes:The cancer microbiome - June 2019, The Healthy Microbiome—What Is the Definition of a Healthy Gut Microbiome? - Jan 2021, The gut microbiome in neurological disorders - Feb 2020, Understanding the role of the gut microbiome in gastrointestinal cancer: A review -Jan 2023, The human microbiome and COVID-19: A systematic review - June 2021, *Interaction between drugs and the gut microbiome - July 2020