ORLANDO, Fla. — An age-independent correlation of osteoporosis and aortic calcification, identified in several studies, may have implications for decisions about treatment of postmenopausal women.

“We are losing mineral from the skeleton and gaining mineral in our arteries,” said Linda Demer, MD, PhD. “The rate of progression of aortic calcification correlates with the progression of osteoporosis, independently of age.”

Speaking at the recent American Heart Association Scientific Sessions 2003, Demer said there is “cross talk” between treatment of osteoporosis and treatment of atherosclerosis. “When we use drugs to prevent osteoclastic resorption, we may also be affecting the artery wall. There is growing evidence that there are resorptive cells in the artery walls that are resorbing the mineral. They have all the same markers as the osteoclasts that are present in bone.”

Demer is the Guthman Professor of Medicine and Physiology and vice chair of the department of medicine/cardiology at UCLA.


Increases with age

Vascular calcification has clinical significance, Demer said, although she said that theory is somewhat controversial. The survival rate in coronary calcification is significantly reduced independently of age, with its severity being predictive of cardiac death.

Studies of tissues in carotid endarterectomy and cardiac valves have found that approximately 80% of those tissues are calcified where there is plaque. About 13% to 15% of those tissues actually have bone.

Demer said that there are transitional stages that indicate “amorphous calcified matrix — what you see in 80% of cases — is always closely related to bone. The bone is forming on top of the calcified matrix through transitional states that are basically identical to embryonic bone formation, a process of endochondral ossification.” At the molecular level, there are identical features between artery wall calcification and bone, she said.


Calcification and hyperlipidemia

There is also a close correlation between vascular calcification and hyperlipidemia. People who are hyperlipidemic tend to have more calcification independently of age. “We studied this in in vitro models and found that, indeed, markers of bone in the master cells build up when the cells are treated with lipids.

“To our surprise, we also found that bone cells treated with the same atherogenic lipids had decreased markers of differentiation. The immature bone cells that are responsible for the mineralization and bone formation located in the subendothelial space is precisely where lipids are deposited.”

Bisphosphonates, indicated for treatment of osteoporosis, can affect artery wall calcification, Demer said. Bisphosphonates inhibit both calcification and resorption in bone and also inhibit calcification in artery walls. While they appear to reduce progression of calcification in the artery wall, they may inhibit resorption in the artery wall, Demer said.

Vitamin D both increases resorption and decreases calcification in bone, but it increases calcification in the artery wall. Researchers are unsure, however, whether the calcium in calcium supplements that are given to postmenopausal women is going to the bone or to the artery wall.


Action of estrogen

The action of estrogen seems to have a paradoxical response, with researchers having questions about whether it promotes vascular calcification. “These questions need to be answered; we need to make sure that we are not doing harm,” she said.

A possible explanation for this apparent opposite effect in the artery wall and bone is that the process could be an ultimate immune defense to a perceived infectious process. “In chronic infection or in chronic inflammation, induced by inflammatory lipids, the body turns on responses to infection that are developed through evolution. The response is to switch identity.”

As a defensive process, the soft tissues build a wall of mineral or bone around an unresolved infection. “We end up with hardening of soft tissues and softening of our hard tissues due to a chronic inflammatory response to perceived infection,” Demer said.


           For more information:

• Demer L. Special session VII: Cardiovascular disease in women: basic science, imaging and outcomes. Vascular calcification in women: imaging as predictors of disease. Presented at the American Heart Association Scientific Sessions 2003. Nov. 9-12, 2003. Orlando, Fla.