Rastelli AL, Taylor ME, Gao F et al.
Washington University School of Medicine, St Louis, MO, USA.
Breast Cancer Res Treat 2011;129:107–16.
Editor’s note: The etiology of the well-described association between aromatase inhibitors and musculoskeletal symptoms remains unclear, but this common side-effect is, as noted elsewhere in this issue of CML – Breast Cancer, underestimated in its frequency and a major cause of therapy discontinuation with this class of drug (Breast Cancer Res Treat 2011;128:553–61, p155). Observational studies have suggested that vitamin D supplementation may ameliorate some of these symptoms. Mechanistically, it is suggested that the estrogen deficiency induced by aromatase inhibitors reduces the activity of the enzyme responsible for the conversion of calcidiol to calcitriol. It is also suggested that aromatase inhibitor therapy may increase the requirement for vitamin D through competition with hepatic CYP450 enzymes. In addition, low vitamin D levels may lead to secondary hyperparathyroidism and deposition of collagen matrix may lead to expansion of sub-periostial tissue and associated discomfort.