Blocking estrogen signals in the brain could help treat osteoporosis

Osteoporosis is a condition in which the bones become so weak, even the simplest actions such as coughing can make a fracture. This fragility is caused by a disruption in the recycling process that healthy bone tissue goes through. More than 200 million people worldwide suffer from this condition; however, women are at a higher risk than men because of the declining level of the estrogen hormone during menopause.

Estrogen’s purpose of regulating reproduction in the female body is known, but the role it plays in the brain remains a mystery. According to LiveScience, estrogen also works with vitamin D and calcium to maintain the regulation of the cycle that breaks down and rebuilds bones. Naturally, as the levels of estrogen in the body decline with aging, so does the rate at which bones are rebuilt. As time progresses it becomes more and more difficult for the body to keep up with the deceleration of this process, and the body begins to break down more bones than it manufactures.

Bones like the femur normally become weak and porous in aging mice (71 weeks, left), but an experimental change in brain signaling led to much denser and stronger bones at the same age (right). Credit Candice Herber / UCSF Core Center for Musculoskeletal Biology & Medicine (CCMBM).

Curious about the effects of estrogen in the brain, colleagues at UCLA and UCSF conducted a study published in Nature Communications involving the blocking of estrogen receptors in the brain of female mice. This caused the mice to gain weight and become less active. To the team’s surprise, the weight gain was due to an 800 percent increase in bone mass. Aside from an increased density, the bones of the animals also had an increase in strength. This increased strength and density did not falter as the mice aged.

The conclusion that the researchers came to is that estrogen plays a different role in the blood than it does in the brain. In the blood, estrogen contributes to bone stability, while in the brain, estrogen seems to limit bone formation. When testing the deletion of estrogen receptors in the hypothalamus, they hypothesized “estrogen must normally signal these neurons to shift energy away from bone growth, but that deleting the estrogen receptors had reversed that shift”.

The scientists involved in the study found that they were able to reverse existing bone degeneration in the mice using the same method. The press release regarding this study states that this “fortuitous discovery may have uncovered a totally novel biological pathway by which the brain regulates bone density”. If this method is proven to be safe and successful, it could lead to a new way to treat osteoporosis in humans, with less side effects than estrogen replacement therapy.

If you are interested in studies related to bones or osteoporosis, you may be interested in our related reagents from academic laboratories worldwide, including: