Researchers at the Van Andel Institute have identified a significant factor contributing to low bone density, a discovery that holds the potential for enhanced treatments with fewer side effects for women suffering from osteoporosis.
The study, authored by VAI Associate Professors Connie M. Krawczyk, Ph.D., and Tao Yang, Ph.D., was published in Science Advances this month. Their research centers on the loss of an epigenetic modulator known as KDM5C, which has been found to preserve bone mass in mice.
KDM5C plays a crucial role by modifying epigenetic “marks,” akin to molecular “on” and “off” switches, which regulate when and where DNA instructions are executed.
Dr. Tao Yang stated, “Osteoporosis is a prevalent condition that can have severe consequences.
KDM5C emerges as a promising target for the treatment of low bone mass in women due to its high specificity. We are hopeful that our findings will contribute to the development of improved therapies.”
Osteoporosis affects nearly 19% of women aged 50 and older in the United States, primarily impacting the hips and lower spine.
This condition weakens bones, elevating the risk of fractures and posing substantial threats to overall health and quality of life.
While various medications are approved for osteoporosis treatment, concerns about rare and severe side effects often deter their use.
Hormone-based therapies involving estrogen are also an option, but they are typically recommended only for low-dose, short-term application due in part to concerns about an increased cancer risk.
It is well-established that women tend to have lower bone mass compared to men throughout their lives. This bone mass loss accelerates during menopause, significantly increasing the risk of osteoporosis and associated fractures as women age.
To unravel the underlying reasons for this gender-based discrepancy, Drs. Krawczyk, Yang, and their research teams examined the differences in bone regulation between male and female mice.
These mice serve as valuable models for studying human health and disease due to their physiological similarities to humans.
The researchers specifically focused on osteoclasts, specialized cells responsible for maintaining bone health by breaking down and recycling old bone tissue.
Their investigation revealed that reducing KDM5C levels disrupted the energy production process within osteoclasts, slowing down the bone recycling process and preserving bone mass.
Significantly, KDM5C is closely linked to X chromosomes, which means it is more active in females than in males.
Dr. Krawczyk explained, “Reducing KDM5C levels is akin to turning off an overly active recycling process. The result is an increase in bone mass, leading to stronger bones.
We are very enthusiastic about this discovery and anticipate further studies to refine our findings. Ultimately, we hope that these insights will make a meaningful difference in the lives of individuals with osteoporosis.”
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The research findings can be found in Science Advances.
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