Bone protection by estrens occurs through non-tissue-selective activation of the androgen receptor

A new study appearing in the September issue of the Journal of Clinical Investigation indicates that caution might be needed if a new group of drugs known as estrens are to be developed for the treatment of osteoporosis.

The researchers found that although estrens improved bone strength in mice with osteoporosis, they also had adverse effects on reproductive organs and human breast cancer cells.

Many individuals, in particular women who have gone through the menopause, suffer from osteoporosis -- a disease in which the bones become fragile and highly susceptible to fracture. Bone strength is naturally maintained by a group of hormones known as sex hormones (for example, estrogen). However, unnaturally high levels of these hormones cause cancer of the reproductive organs and breast tissue, meaning that they cannot be used to treat individuals with osteoporosis. So, researchers have long been searching for estrogen-like molecules that increase bone strength but do not cause cancer. Recently, a new set of molecules (known as estrens) said to have these properties were identified. However, the wisdom behind developing estrens for use in the clinic is questioned by Roland Baron and colleagues from Yale University. They showed that although mice with osteoporosis treated with estrens showed some improvement in bone strength, their reproductive organs increased in size. Furthermore, estrens induced the proliferation of human breast cancer cells. This study indicates that estrens might not be the sought after estrogen-like molecules that improve bone strength but do not cause cancer, and has important implications for their clinical development.

In an accompanying commentary, Ushma S. Neill from The Journal of Clinical Investigation discusses the evidence for and against the use of estrens to treat osteoporosis, and concludes that we will have to wait for the completion of clinical trials before we have a definitive answer.