The role of vitamin A and retinoic acid receptor signaling in post-natal maintenance of bone

• Retinoids regulate post-natal bone.
• Retinoids regulate bone by direct and indirect actions.
• The effect of retinoids on bone in vivo is highly site- and dose-specific.
• Targeting retinoid signaling has therapeutic potential in bone diseases.

Vitamin A and retinoid derivatives are recognized as morphogens that govern body patterning and skeletogenesis, producing profound defects when in excess. In post-natal bone, both high and low levels of vitamin A are associated with poor bone heath and elevated risk of fractures. Despite this, the precise mechanism of how retinoids induce post-natal bone changes remains elusive. Numerous studies have been performed to discover how retinoids induce these changes, revealing a complex morphogenic regulation of bone through interplay of different cell types. This review will discuss the direct and indirect effects of retinoids on mediators of bone turnover focusing on differentiation and activity of osteoblasts and osteoclasts and explains why some discrepancies in this field have arisen. Importantly, the overall effect of retinoids on the skeleton is highly site-specific, likely due to differential regulation of osteoblasts and osteoclasts at trabecular vs. cortical periosteal and endosteal bone surfaces. Further investigation is required to discover the direct gene targets of retinoic acid receptors (RARs) and molecular mechanisms through which these changes occur. A clear role for RARs in regulating bone is now accepted and the therapeutic potential of retinoids in treating bone diseases has been established.