In female individuals, oestradiol preserves bone mass. However, oestradiol levels drop during lactation, which is also a time when calcium is being removed from the maternal bone. How bone mass is maintained in lactating female individuals has been unclear. A study published in Nature has now identified a new mechanism for maintaining bone mass, which involves brain–bone crosstalk.

Next, the researchers conducted single-cell RNA sequencing on osteochondral skeletal stem cells from mutant female mice, which gave limited insights. The observation that a high-fat diet degraded the bone phenotype of the mutant mice enabled Muriel Babey, co-lead on this study, to narrow down the list of potential factors. Of these, CCN3 was found to be present near the third ventricle in female Esr1Nkx2-1-cre mice, but was absent in the wild-type mice. Furthermore, CCN3 expression correlated well with the appearance of the bone phenotype and was co-localized with KISS1 neurons in the female mutant mice.