ERR receptors as potential targets in osteoporosis

The bone fragility and increased fracture risk associated with osteoporosis in post-menopausal women is a major public health concern. Current treatments for osteoporosis relying on hormone replacement therapies are suspected to have an association with increased breast cancer risk, highlighting the need for identifying new potential targets in bone. Recent data suggest that the estrogen-related receptor (ERR)a, an orphan nuclear receptor, represses osteoblast differentiation, and that its deletion in knockout mouse models results in increased mineral density. Furthermore, modulation of ERR alpha activity reduces proliferation and tumorigenesis of breast cancer cells. These results indicated that inhibition of ERRa might provide a treatment for osteoporosis without displaying adverse effects in breast cancer. This review focuses on the role of the ERR receptors, and in particular ERRa, in the differentiation of bone precursor cells and its consequences on bone homeostasis, and discusses the possible grounds for the discrepancies reported in the literature.