Bone problems are significant health issues affecting individuals' quality of life and overall health. Among these issues, osteoporosis stands out as a major challenge for bone health, especially in women, where the risk of developing it significantly increases after menopause. Osteoporosis is a condition characterized by reduced bone density and weakened structure, making bones more susceptible to fractures, even from minor injuries. This condition usually develops gradually without noticeable symptoms until a fracture or significant health issue occurs.
Understanding the relationship between hormones and bone health is key to effectively addressing osteoporosis, which is what a study published in *Nature* has revealed. Scientists have long wondered why mothers' bones do not shrink during pregnancy and breastfeeding, which deplete vitamins and calcium from the mother's body. Researchers at the University of California, San Francisco, seem to have found the answer. They discovered a completely new hormone in female mice that remarkably promotes the growth of strong and dense bones. Neuroscientists named this hormone the Maternal Brain Hormone (MBH); it works to build strong and healthy bones in mice of both sexes and all ages.
Most studies have focused on the effect of estrogen on bones. Estrogen is a sex hormone that plays a role in bone building and has widespread effects on the brain. While estrogen levels fluctuate throughout life, they decrease significantly after menopause, making older women more susceptible to the bone-weakening effects of osteoporosis. Estrogen levels also drop in breastfeeding mothers, which slows bone growth. Simultaneously, the mother's body absorbs calcium from her bones to continue nourishing her newborn, putting the bones at greater risk.
In 2019, the Ingraham lab at the University of California, San Francisco, was surprised to find that blocking estrogen in a specific part of a female mouse's brain actually improved the animal's bone strength significantly, raising questions about the existence of another bone-building hormone, which has since been discovered. The discovered hormone, or MBH, is a known protein called CCN3. It is secreted by nerve cells in a part of the brain called the arcuate nucleus and plays a role in reproduction and puberty. It was found that during lactation in mice, these nerve cells increase MBH production as estrogen decreases.
This hormone has been shown to stimulate stem cell activity in bone tissues in both mice and humans. Remarkably, elevated levels of this hormone in live mice of both sexes and all ages led to enhanced bone remodeling and accelerated fracture repair. Although estrogen levels return to normal once breastfeeding stops, both the mother and her offspring would not be in a healthy state without the protective nature of MBH. In experiments conducted on live mice, when MBH production was artificially inhibited, researchers found that the mother lost significantly more bone density than usual and her pups lost weight rapidly. In contrast, when researchers introduced additional amounts of the hormone to both young and old mice, male and female, the animals showed substantial increases in bone mass and strength within weeks. Even for older female mice with very low estrogen levels, treatment with MBH resulted in a more than doubling of their bone mass.
Thomas Ambrosi, a stem cell biologist from the University of California, Davis, remarked, "There are some cases where bones that are not overly mineralized can be weaker and break more easily, but when we tested these bones, they turned out to be much stronger than usual. We have never been able to achieve this level of mineralization and healing result with any other strategy."
There are also more positive outcomes. When researchers encapsulated the discovered hormone in a hydrogel patch and applied it directly to a broken bone in an older mouse, it promoted the growth of the fractured bone. However, further research is needed to determine how successful these results will be in humans. During breastfeeding, humans temporarily lose about 10% of their bone density, which is significantly lower than that seen in mice.
Ingraham explains, "Bone loss does not only occur in women after menopause; it often happens in breast cancer survivors taking certain hormone inhibitors; in young female athletes undergoing intensive training; and in older men who have lower relative survival rates than women after hip fractures."
