Vitamin B12 as a Regulator of Bone Health

In the early 1920s, the anti-anaemic effect of liver-rich diet had been recognized. The anti-anaemic substance from the liver was isolated by 1950 and called ‘vitamin B₁₂’ (hereafter B₁₂). It took another 20 years to structurally define and chemically synthesize B₁₂ in its pure form. Since then, it has been recognized that B₁₂ modulates a variety of biological systems, from immune system to bone homeostasis. Recent clinical studies have shown that B₁₂ deficiency is likely to be an important etiological factor in the pathogenesis of bone degeneration. In this regard, either observational studies that aimed to verify an association between low B₁₂ level and bone mass, or clinical trials on the effect of B₁₂ as a supplementary treatment in low bone mass patients have been presented in the emerging clinical literature. Recently, we created a mouse genetic model of B₁₂ deficiency to elucidate its mode of action by genetic deletion of gastric intrinsic factor, a protein essential for the absorption of B₁₂ from the gut. This has led to the identification of a novel gut–liver-bone axis that has the potential to be pharmacologically targeted for treating low bone mass diseases in humans. In this review, we revisit the history of B₁₂ from its discovery in the early 20th century to the elucidation of its mode of action in the bone till date.