Millions of women could benefit from improved osteoporosis treatments after scientists discovery of a key driver of low bone density.
Around 200 million women worldwide are believed to be affected by osteoporosis, a potentially serious health condition that weakens bones, making them more fragile and therefore likely to break.
While men can develop the bone disease, 80% of sufferers are women, mainly as a result of falling oestrogen hormone levels during the menopause. Oestrogen is essential for healthy bones. But as levels of the hormone drop, women undergo rapid bone loss over several years.
Osteoporosis’ prevalence increases with age, with 49% of women 50-plus affected by it.
In the worst cases something as simple as coughing or having a minor bump can result in a broken bone. Fractures can cause long-term health problems and even threaten life. A significant number of sufferers who break their hip die within one year of the injury.
But now a team at Van Andel Institute in Grand Rapids in the United States say they have pinpointed a gene that could help preserve bone mass.
The research described in a study published in Science Advances reveals that loss of an epigenetic modulator, KDM5C, protects bone mass in mice. KDM5C works by altering epigenetic marks, which are akin to ‘on’ and ‘off’ switches that ensure instructions written in DNA are used at the right time and place.
Van Andel Institute (VAI) associate professor, Tao Yang, PhD, one of the report’s authors, said: “Osteoporosis is a common disease that can have debilitating outcomes. KDM5C is a promising target to treat low bone mass in women because it is highly specific. We’re hopeful that our findings will contribute to improved therapies.”
Several medications are approved to treat osteoporosis, but the study team say fears of rare, severe side effects are often a barrier for their use.
Treatments that can leverage oestrogen are also available, but are only recommended for low dose, short-term use due in part to associations with a cancer risk.
It has long been known that women experience disproportionately lower bone mass than men throughout their lives, a situation that is accelerated with menopause, increasing the risk of osteoporosis and associated fractures.
Dr Connie Krawczyk. Credit: Van Andel Institute
To figure out why this happens, Dr Yang, fellow VAI associate professor, Connie Krawczyk, and their teams looked at the differences in the ways bone is regulated in male and female mice, which share many similarities with humans and are important models for studying health and disease.
They focused on specialised cells called osteoclasts, which help maintain bone health by breaking down and recycling old bone.
The researchers found reducing KDM5C disrupted cellular energy production in osteoclasts, which slowed down the recycling process and preserved bone mass. Importantly, KDM5C is linked to X chromosomes, which means it is more active in females than in males.
Dr Krawczyk said: “Lowering KDM5C levels is like flipping a switch to stop an overactive recycling process. The result is more bone mass, which ultimately means stronger bones.
“We’re very excited about this work and look forward to carrying out future studies to refine our findings. At the end of the day, we hope these insights make a difference for people with osteoporosis.”