Breastfeeding can put stress on your bones. Brain hormones may protect your bones.

“This study has uncovered a new direct link between the hypothalamus and bone, which is completely unexpected,” says Sundeep Khosla, a bone researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study.

In a new study, scientists set out to find out why blocking estrogen receptors in the hypothalamus produces female mice with particularly high bone density. Compared to normal mice, the mutant mice had “a huge increase in the number of bone stem cells,” says Thomas Ambrosi, a stem cell biologist at the University of California, Davis.

Since the hypothalamus also plays a role in appetite, the researchers looked at diet to see how it affected bone density and the hormones it produces. A key piece of the puzzle fell into place when the team found that mutant mice fed a high-fat diet had normal bone density. By analyzing which bone-strengthening factors were reduced in those mice, Muriel Baby, an endocrinologist at the University of California, San Francisco, says the team was able to narrow the list of potential candidates from hundreds to a handful.

The scientists then added the substance to mouse stem cells in petri dishes, and found that when treated with CCN3, bone fragments formed. The team also found that CCN3 levels in female mice spiked during lactation, suggesting that CCN3 plays a role in maintaining maternal bone strength during lactation, when estrogen levels drop.

Next, Ambrosi’s team tested CCN3 in older mice with bone fractures that normally do not heal well. Applying a hydrogel patch containing the hormone to the injured area stimulated bone formation, leading to faster recovery. If the hormone acts on human skeletal stem cells in a similar way, it could lead to new treatments for osteoporosis (Serial Number: September 20, 2018).

While there are many drugs that prevent bone loss, Khosla says, “We’re still limited in what we can do to stimulate bone formation, especially in a sustained manner—over years rather than months.” Because of CCN3’s tissue-forming properties, future drugs based on the hormone could potentially increase bone regeneration.

The study “highlights how much biology and physiology is happening during the reproductive life cycle,” said co-author William Kraus, a pharmacologist at UC San Francisco. “There’s likely a lot of biology that’s still to be unraveled.”