April 28, 2011 -- An early report of a new study shows that the first-generation bisphosphonate, Didronel, in combination with the cholesterol drug Lipitor reduced abdominal aortic plaques by about 12% in people with high cholesterol, compared to 1% in people on Lipitor alone.
Those in the combination-therapy group also had fewer serious heart events over two years, like heart attacks, procedures to open clogged arteries, hospital admissions, and deaths from heart disease, than those who took Lipitor alone.
Didronel is FDA-approved to treat osteoporosis and Paget’s disease, which causes bones to form abnormally, making them enlarged and brittle.
Didronel is “a first-generation bisphosphonate, and it has weaker therapeutic ability in inhibiting bone resorption, but stronger ability in preventing vascular calcification, than that of newer generation bisphosphonates,” says study researcher Tetsuya Kawahara, MD, of the University of Calgary in Alberta, Canada.
The research was presented at the American Heart Association’s 2011 Arteriosclerosis, Thrombosis and Vascular Biology Scientific Sessions in Chicago. Experts say it adds to a growing body of research suggesting that bisphosphonate drugs, particularly the older, non-nitrogen containing bisphosphonates, may also help treat heart disease.
“There have been some other, smaller studies done that have looked at carotid artery thickness in response to bisphosphonates, and it was shown that bisphosphonates reduce the thickness of the carotid artery,” says Ravi Dave, MD, a cardiologist and associate professor of medicine at the University of California, Los Angeles.
“Now, with the aging of the population that is at risk for having all these plaques, we need to put them on Lipitor and they’re also on bisphosphonates, it’s an added sort of benefit for these patients,” says Dave, who was not involved in the research.
But other experts caution that the research is too preliminary to act on, saying that larger, better-controlled studies are needed before bisphosphonates can be considered a valid treatment for heart disease.
Some studies have also suggested that bisphosphonates may be linked to atrial fibrillation, or disturbance of the heart’s pumping rhythm.
Bone Drugs and Atherosclerosis
The study followed 251 people who had high cholesterol with no other symptoms.
Participants were randomly assigned to take either 20 milligrams of Lipitor each day or to take Lipitor with 400 milligrams of Didronel.
Both groups had similar reductions in cholesterol: 44% in the combination-therapy group and 45% in the Lipitor group.
And they had similar reductions in the size of plaques in the thoracic aorta, the part of the artery that sits inside the chest, which were reduced by 13% in the Lipitor group compared to 15% in the combination therapy group.
Changes to plaques in the abdominal aorta, the part that travels near the stomach and past the kidneys, however, were substantially different, with a 1% reduction in the Lipitor-only group compared to a 12% reduction in the combination therapy group.
So what might account for changes in plaques to one part of the artery but not the other?
“The reason for this discrepancy may be the difference in plaque constituents between the thoracic and abdominal aorta,” Kawahara says. “In the thoracic aorta, fatty streaks are common, while in the abdominal aorta, fibroblasts and calcified plaques are frequently observed.”
Experts think bisphosphonates may slow the formation of plaques because they block enzymes important to making cholesterol, and they appear to suppress white blood cells that are a key part of plaque formation.
The researchers agreed, however, that studies are needed to repeat the findings and clarify the drugs’ mechanism of action in heart disease before bisphosphonates can be considered to treat heart disease.