Osteoporosis–cardiovascular disease link explained
MedWire News: T-lymphocyte stimulation by oxidized lipids may explain the link between osteoporosis and cardiovascular disease, say US scientists.
"We've known that osteoporosis patients have higher cholesterol levels, more severe clogging of the heart arteries and increased risk for stroke. We also knew that drugs that lower cholesterol reduce bone fractures, too," explained author Rita Effros, from the University of California in Los Angeles. "What we didn't understand was why,” she said.
Receptor activator of NFκB ligand (RANKL) is produced by activated T-lymphocytes and has been shown to stimulate maturation and activation of bone-resorbing osteoclasts, the team explains.
Recognizing that oxidized lipids alter T lymphocyte function, the researchers examined whether short-term exposure of human T lymphocytes from healthy donors with normal lipid levels to minimally oxidized low density lipoprotein (LDL) would significantly increase RANKL production compared with native LDL.
As reported in the journal Clinical Immunology, RANKL concentration was significantly higher in the supernatant of activated T lymphocytes in the presence of oxidized LDL than native LDL or buffer alone. Unexpectedly, a similar pattern also occurred with inactive T lymphocytes.
These findings were confirmed in an experiment in mice, which showed that animals fed a high-fat diet had significantly lower femoral bone mineral content than mice fed a standard diet. T lymphocytes from the high-fat diet animals had significantly higher levels of RANKL messenger RNA and RANKL protein.
“The in vitro data on human T lymphocytes, and the murine in vivo model of hyperlipidemia-induced bone loss indicate that exposure to oxidized lipids enhances T lymphocyte RANKL production,” the researchers write.
They conclude: “These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.”
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By Lynda Williams