Researchers have identified a new hormone, CCN3, that significantly strengthens bones. This discovery, made while studying how breastfeeding women maintain bone density, could transform the treatment of osteoporosis and bone fractures.
Published in Nature, the new study reveals that CCN3 promotes bone formation and repair in both male and female mice, offering new hope for millions suffering from bone-related conditions.
About the Study
Researchers at University of California (UC) San Francisco (UCSF) and UC Davis collaborated to solve a long-standing medical mystery: how breastfeeding women maintain strong bones despite the significant loss of calcium needed for milk production.
In lactating mothers, the high demand for calcium needed for milk production can lead to significant bone loss. Normally, estrogen is protective for women, helping to counteract bone loss by promoting bone formation. However, its levels drop sharply during breastfeeding. Despite this drop, breastfeeding women seldom experience osteoporosis or bone fractures, suggesting another factor is at work to protect their bones.
Previous research published in Nature found that blocking a specific estrogen receptor in certain brain neurons of female mice led to significant increases in bone mass. Suspecting a hormone in the blood was responsible, the study researchers conducted an exhaustive search and identified a hormone called Cellular Communication Network Factor 3, or CCN3, as the bone-building factor in these mutant females.
Dubbed the “lactation-induced brain hormone,” CCN3 is found in the brains of lactating mice and plays a crucial role in maintaining bone strength during lactation.
“One of the remarkable things about these findings is that if we hadn’t been studying female mice, which unfortunately is the norm in biomedical research, then we could have completely missed out on this finding,” Holly Ingraham, senior author of the new study and professor of cellular molecular pharmacology at UCSF, said in a press release.
The researchers discovered that increased CCN3 levels in mice showed significant bone mass and strength improvements, even in older mice and those lacking estrogen. Tests demonstrated that mice with higher CCN3 levels had much stronger bones, as the CCN3 hormone stimulated skeletal stem cell activity. Without CCN3, these mice rapidly lost bone density, and their offspring also suffered.
Dr. Sundeep Khosla, a Mayo Clinic physician who runs the Osteoporosis and Bone Biology Laboratory, explained the significance of CCN3, known as the “maternal brain hormone” to The Epoch Times. “Anytime you identify a completely new pathway to regulate bone from the brain, that’s scientifically very interesting.”
Dr. Khosla noted that CCN3 prevents the skeleton from dissolving during lactation while stimulating bone formation for new calcium deposition. “It adds another piece to our understanding of what happens with lactation.”
Impact on Osteoporosis
Osteoporosis, a condition characterized by weakened bones and an increased risk of fractures, is a significant global health issue. According to the U.S. Department of Health and Human Services, an estimated 10 million Americans have osteoporosis, with women comprising 80 percent of those affected. Additionally, the Centers for Disease Control and Prevention reports that about 44 million people have low bone mass, putting them at increased risk for osteoporosis.
Globally, osteoporosis affects around 200 million people, leading to millions of fractures annually, primarily in the hip, spine, and wrist. These fractures can cause severe pain, disability, and increased mortality, underscoring the urgent need for effective treatments such as those potentially offered by CCN3.
The financial burden of osteoporosis, estimated to cost $25 billion annually in the United States, could be significantly alleviated by treatments derived from CCN3.
Dr. Khosla highlighted the potential of CCN3 in addressing osteoporosis, emphasizing its scientific promise and economic implications. While current drugs are effective when used correctly, they are often underutilized due to fears of side effects, he said. He stressed the need for better education for both physicians and patients to optimize the use of these cost-effective treatments.
“New drugs that may result from CCN3 could be particularly beneficial for those with osteoporosis” he stated. Depending on the cost of the drug, it could potentially reduce the substantial financial burden of osteoporosis.
Potential Benefits and Future Applications
The discovery of CCN3’s role in bone health extends beyond understanding lactation. This hormone could have significant implications for accelerating fracture repair and treating osteoporosis.
In a conversation with The Epoch Times, lead author Dr. Muriel Babey explained that researchers developed a hydrogel patch that slowly releases CCN3 at bone fracture sites, leading to faster and stronger healing in elderly mice. The treated fractures healed much quicker and were stronger than those without the hormone treatment.
“We’ve never been able to achieve this kind of mineralization and healing outcome with any other strategy,” said Dr. Thomas Ambrosi, a co-author of the study from UC Davis in the press release.
While the current study focuses on mice, the implications for human health are promising. The next steps include clinical trials to test CCN3’s effectiveness in humans and further exploration of its potential applications in bone health treatments.
Dr. Khosla highlighted the limitations of current osteoporosis treatments. While drugs like bisphosphonates can prevent bone loss, the ability to reverse osteoporosis is still limited.
“We need new approaches to build bone back up,” Dr. Khosla stated, noting that existing drugs often stop working over time. He expressed hope that CCN3 could offer more sustained and robust effects in stimulating bone formation, possibly in combination with other treatments.
Dr. Babey explained that bone loss affects not only post-menopausal women but also breast cancer survivors taking hormone blockers, younger elite female athletes, and older men, who have a lower survival rate after hip fractures compared to women. If CCN3 could increase bone mass in all these groups, it would be a significant breakthrough.
With clinical trials on the horizon, CCN3 holds promise for revolutionizing bone health treatment and improving the quality of life for millions worldwide.
