New research suggests the liver plays a previously unrecognized role in bone health, but only in males.
A McGill University-led study published in Matrix Biology found that a protein made in the liver helps regulate bone growth in male mice, but not in females. The findings may help explain why men with liver disease are more likely to experience bone loss.
The protein, known as plasma fibronectin, is naturally present in blood at higher levels in men than in women, declines when the liver is damaged and builds up in bone to modulate bone formation. This suggests men rely more heavily on the protein to maintain bone strength than do women.
“About 60 per cent of osteoporosis cases in men are secondary to other underlying health conditions,” said senior author Mari Tuulia Kaartinen , Associate Professor in McGill’s Faculty of Dental Medicine and Oral Health Sciences. “Our findings suggest this protein may be one of the biological links connecting liver disease to bone loss.”
Osteoporosis has traditionally been viewed as a disease driven by aging and processes within the bone itself, and it has been more commonly associated with women. At least one in three women and one in five men will break a bone due to osteoporosis in their lifetime.
“We know women lose bone mass largely because of hormonal changes at menopause, but men lose bone too, especially after age 50, but the reasons have been less understood,” said Kaartinen.
In lab experiments, the researchers selectively turned off the fibronectin gene in the liver, preventing the protein from releasing into the bloodstream. Only male mice were less able to build strong bone when the protein was missing.
“This is another example of how diseases can develop differently between the sexes,” said Kaartinen. “Better accounting for biological differences in medical research is essential for developing more precise approaches to prevention and care.”
More broadly, the findings add to a growing awareness of osteoporosis as a whole-body condition rather than one that originates in bone alone, she added.
“ Liver-derived, circulating plasma fibronectin regulates trabecular bone mass and bone formation in adult male mice and its levels in sera associates with bone density in aging men ” by Mahdokht Mahmoodi and Mari T. Kaartinen et al. was published in Matrix Biology. Funding was provided by the Canadian Institutes of Health Research.
Matrix Biology
Experimental study
Animals
Liver-derived, circulating plasma fibronectin regulates trabecular bone mass and bone formation in adult male mice and its levels in sera associates with bone density in aging men
7-Dec-2025