Researchers have discovered a new hormone that could be a breakthrough in the treatment of osteoporosis, a debilitating disease that results in brittle bones.

Over 200 million people worldwide suffer from osteoporosis, a condition that weakens bones and causes frequent fractures. Women are particularly at risk after menopause due to lower estrogen levels, which help form bones. Interestingly, despite low estrogen levels during breastfeeding, the bones of breastfeeding women stay strong even as they lose calcium to milk, indicating that another factor may promote bone growth.

The researchers at UCSF and UC Davis who investigated the mystery discovered during a mice study that a maternal brain hormone (CCN3) increases bone density and strength in female mice. The results of the study were published in the journal Nature.

The researchers had earlier found that blocking a specific estrogen receptor in certain brain neurons led to a significant increase in bone mass in female mice. Suspecting a blood hormone was responsible, researchers searched and identified CCN3 as the key factor.

Although CCN3 did not seem like a typical neuron-secreted hormone, its presence in the brains of lactating female mice confirmed its role. The researchers noted that without CCN3, lactating mice lost bone, and their babies lost weight. The researchers now call CCN3 the Maternal Brain Hormone (MBH).

"One of the remarkable things about these findings is that if we had not been studying female mice, which unfortunately is the norm in biomedical research, then we could have completely missed out on this finding. It underscores just how important it is to look at both male and female animals across the lifespan to get a full understanding of biology," Holly Ingraham, senior author of the study, said in a news release.

When researchers increased CCN3 levels in young adult and older mice, their bone mass and strength grew significantly within weeks. In some female mice without estrogen or those very old, CCN3 more than doubled their bone mass.

"There are some situations where highly mineralized bones are not better; they can be weaker and actually break more easily. But when we tested these bones, they turned out to be much stronger than usual," said Thomas Ambrosi, a scientific collaborator of the study.

The researchers also observed that the bone stem cells were more prone to generate new bone cells when exposed to CCN3. To see if CCN3 could aid bone healing, researchers developed a hydrogel patch that would slowly release CCN3 at the site of a bone fracture. Normally, fractures are hard to heal in elderly mice, but the CCN3 patch promoted new bone growth at the fracture site, leading to a more youthful healing process.

"We've never been able to achieve this kind of mineralization and healing outcome with any other strategy. We're really excited to follow it up and potentially apply CCN3 in the context of other problems, such as regrowing cartilage," Ambrosi said.

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