Clotting factor proteins may affect bone cell activity, study finds
Findings may explain prevalence of bone problems in hemophilia
Clotting proteins that are missing or are defective in hemophilia can directly affect the activity of cells responsible for maintaining bone health, a study found.
The findings shed new light on why bone problems are a common issue among people with hemophilia, researchers said.
The study, “Effects of coagulation factors on bone cells and consequences of their absence in haemophilia a patients,” was published in Scientific Reports.
Hemophilias are disorders in which certain blood clotting factors are either absent or dysfunctional, impairing blood clotting and increasing patients’ susceptibility to excessive and prolonged bleeding. Each type of hemophilia is associated with the lack of a specific clotting factor: factor VIII (FVIII) in the case of hemophilia A and factor IX (FIX) in hemophilia B.
It’s long been known that people with hemophilia often have bone health problems, such as unusually weak or fragile bones and high predisposition to fractures, in addition to bleeding symptoms. The biological mechanisms that lead to poor bone health in hemophilia patients are not completely understood.
Cells and bone health
Bone health is primarily controlled by two types of cells, osteoblasts and osteoclasts. Osteoblasts are responsible for making new bone tissue, whereas osteoclasts can break down the dense minerals that make up old or damaged bones. Normally, these two types of cells work in concert to control bone growth and remodeling, but when they get out of sync, problems may arise.
“The direct effects of FVIII and FIX deficiency on bone cells have not been deeply investigated,” the scientists wrote. In an effort to learn more, they conducted a battery of experiments on osteoclasts and osteoblasts derived from cells gathered from healthy donors and/or hemophilia A patients.
They found that in healthy donors, FVIII treatment decreased the formation of bone-destroying osteoclasts and reduced the activity of bone-making osteoblasts.
Consistent with those initial experiments, they found that in hemophilia A patients who are deficient for FVIII, there was an abnormally high production of osteoclasts. Effects on osteoblasts couldn’t be directly assessed in patients because that would require a bone biopsy, which is not required as part of the routine clinical management of hemophilia.
Collectively, the data suggest that the lack of FVIII may lead to irregular bone cell activity that ultimately results in weakened bones for people with hemophilia A. FIX, however, did not substantially affect the activity of osteoclasts or osteoblasts, leading researchers to argue that other mechanisms causing bone problems must be at play in hemophilia B patients.
“These results could be important to understand how coagulation factors deficiency influences bone remodeling activity in haemophilia,” the scientists wrote.
A limitation of this research is that most experiments used just one clotting factor at a time, but in the human body, these proteins are always interacting with each other and with many other proteins simultaneously. The researchers stressed the need for further investigation into how clotting factors affect bone cells, noting that better understanding these mechanisms may help find new ways to improve bone health in people with hemophilia.
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