A long-standing mystery about breastfeeding may have been solved

A newly discovered hormone in mice may solve the long-standing mystery of how adult bones stay strong during the stress of breastfeeding. The finding could lead to new treatments for osteoporosis, a condition in which bones become weak and brittle.

For decades, it was unclear how bones maintain strength during breastfeeding, when the body strips calcium from bones to produce nutrient-rich milk. Breastfeeding also lowers levels of oestrogen, a hormone essential for skeletal health. Despite this, lactation only causes temporary dips in bone mass that are resolved between 6 and 12 months after breastfeeding ends.

While conducting research unrelated to this conundrum, Holly Ingraham at the University of California, San Francisco, and her colleagues found that inhibiting oestrogen production by targeting receptors in an area of the brain’s hypothalamus actually strengthened bones in female mice.

“It was a bit paradoxical because here we’re getting rid of oestrogen signalling, which you think of as being beneficial for bone, and creating females with these extremely dense bones,” says Ingraham.

To figure out why that was, she and her colleagues bred female mice that lacked these oestrogen receptors, which caused them to have unusually strong bones. They then surgically attached the animals to other female mice that had the receptors, connecting their circulatory systems.

After 17 weeks, bone volume increased by 152 per cent, on average, in the mice attached to those with strong bones. This suggested that a substance responsible for strengthening bones was circulating in the blood, so could pass from the mice without the receptors to those with them. Subsequent experiments revealed that this substance was a brain hormone called CCN3.

The researchers then measured CCN3 in the brains of female mice before they became pregnant and after they gave birth, revealing it is only produced during lactation. Moreover, blocking the hormone reduces bone mass in lactating mice, suggesting it may be the mystery molecule preventing bone loss in lactation. This finding also raises the possibility of using CCN3 to repair bone in other contexts.

To explore this further, the researchers applied a patch containing CCN3 to four male mice with bone fractures. An equal number of animals received a patch without the hormone. All of the rodents were 2 years old, roughly equal to 69 years of age in humans.

After three weeks, bone volume was 240 per cent higher, on average, in mice with the CCN3 patch than in those without it. This suggests CCN3 could help treat or even prevent osteoporosis, which affects more than 12 per cent of adults aged 50 or older in the US.

However, we don’t know whether these findings will translate to people, says Ingraham. She and her colleagues are developing a blood test for CCN3, which would enable them to see if the hormone increases in those who are breastfeeding.