The researchers discovered that mice lacking a key estrogen-regulating protein were unable to grow enough bone cells. The finding could lead to new therapies to treat osteoporosis in post-menopausal women.
Osteoporosis affects 10 million Americans, mostly women, limiting their mobility and leading to more than 1.5 million fractures a year, sometimes with deadly consequences.
Bone cells grow and bone density is maintained according to a complex recipe of calcium, vitamin D, growth factors and hormones. As people age, their risk for the bone-thinning disease increases, especially as estrogen levels decline.
Researchers at the Royal Veterinary College in London studied female mice that were bred both with and without a protein called estrogen receptor alpha, or ER-alpha. The hormone estrogen circulates in the bloodstream and binds to certain cells via estrogen receptors, protein molecules that regulate the level of estrogen. In humans, varying amounts of the receptors are present in almost every cell in the body.
Researchers surgically implanted gauges in the shaft of the mice's front legs and measured their response to the strain exerted from bearing a load over two weeks. Normally, when a bone undergoes physical stress, the body forms new bone cells to offset the pressure.
Researchers discovered that mice with active ER-alpha receptors formed three times more new bone than mice without the receptors.
"It explains why estrogen withdrawal results in bone loss," said the study's lead author, Lance Lanyon. The number of estrogen receptors is reduced by lower estrogen levels and diminishes the ability of bone cells to adequately respond.
The study appears in Thursday's issue of the journal Nature.
Lanyon said there is no current osteoporosis therapy involving ER-alpha, but it offers a promising target for new trials for drugs that would stimulate ER-alpha receptors or replace their function in cells.
Other researchers who did not participate in the British study said it demonstrates a possible role ER-alpha may play in menopausal osteoporosis. Dr. Margery Gass, director of the University Hospital Menopause and Osteoporosis Center in Cincinnati, said more research is needed to understand how the number of estrogen receptors relates to bone density in humans.
To help combat bone loss, doctors advise eating calcium-rich diets like green vegetables and milk products, special exercises and often calcium supplements.
Some menopausal women also use estrogen and combination estrogen-progestin therapy. Last summer, a study was published linking estrogen-progestin supplements with heart attacks, strokes and breast cancer. A study is still in progress on the use of estrogen alone.
By Alicia Chang