Two types of estrogen receptors including ER-α and ER-β are known, and they exist in bone mesenchymal stem cells (MSCs), osteoblasts, osteoclasts and also in precursor cells of both types.22 The normal level of estrogen in the body is vital and consuming large amounts of estradiol (for the treatment of osteoporosis) in the long term can cause serious complications in other tissues. This evidence concerns the gene ESR1 and osteoporosis.