Vitamin A Metabolism in Bone Health and Fracture Risk

Vitamin A is a fat‐soluble micronutrient obtained as retinyl esters from animal sources or as provitamin A carotenoids from plants. Following intestinal uptake, hepatic stores of retinol are mobilised and oxidised to all-trans-retinoic acid (ATRA), the bioactive ligand for nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In bone tissue, retinoid signalling modulates the balance between osteoblastic bone formation and osteoclastic bone resorption. Preclinical models consistently show that excess ATRA enhances periosteal bone resorption and suppresses cortical bone formation, whereas deficiency impairs early osteoblast differentiation. Clinically, both low and high serum retinol levels have been linked to diminished bone mineral density and elevated fracture risk in a U-shaped pattern, with effects modified by vitamin D status, age and hormonal milieu. Understanding this dual‐edged influence of vitamin A is critical for developing dietary recommendations and therapeutic strategies to preserve skeletal integrity in ageing and disease.

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Vitamin A Metabolism in Bone Health and Fracture Risk publication trend

The graph below shows the total number of articles in vitamin a metabolism in bone health and fracture risk across all publications each year (not limited to Nature Index journals).

Technical terms

All-trans-retinoic acid (ATRA): The active metabolite of vitamin A that binds nuclear retinoic acid receptors to regulate gene expression.

Retinoic acid receptors (RARs): A family of ligand-activated transcription factors that heterodimerise with RXRs to control retinoid-responsive genes.

Osteoclast: A multinucleated cell responsible for bone resorption, formed by fusion of monocyte-macrophage lineage precursors.

Osteoblast: A mesenchymal-derived cell that produces bone matrix and mediates mineralisation.

Periosteum: The fibrous membrane covering bone surfaces, rich in progenitor cells and osteoclast precursors.

Bone mineral density (BMD): A quantitative measure of mineral content in bone, indicative of strength and fracture risk.

References

1. Vitamin A – discovery, metabolism, receptor signaling and effects on bone mass and fracture susceptibility. Frontiers in Endocrinology (2024).
2. Vitamin A enhanced periosteal osteoclastogenesis is associated with increased number of tissue-derived macrophages/osteoclast progenitors. Journal of Biological Chemistry (2024).
3. The Effect of Vitamin A on Fracture Risk: A Meta-Analysis of Cohort Studies. International Journal of Environmental Research and Public Health (2017).
4. Vitamin A Intake, Serum Vitamin D and Bone Mineral Density: Analysis of the Korea National Health and Nutrition Examination Survey (KNHANES, 2008–2011). Nutrients (2015).