Skeletons in the Closet of Cardiovascular Disease

Atherosclerotic calcification is an actively regulated process, not just passive mineral deposition over time. As osteogenesis and vascular calcification share similar molecular mechanisms, vascular cells play an active role in osteoid formation. That’s why low bone mass is often associated with advanced atherosclerosis and increased risk of stroke and cardiovascular-related death.

Taking those associations into account, pharmacological agents that inhibit bone loss could slow the progression of atherosclerosis and cardiovascular disease (CVD).

The idea that atherosclerosis and osteoporosis have remarkable similarities isn’t new. In fact, it originated in the 1500s when early pathologists Antonio Benivieni and Gabriele Fallopio described heart disease as the degeneration of arteries into bone. Pathologist Rudolph Virchow also believed vascular changes were closely related to ossification. Then, in 1906, biologist and physician C.H. Bunting demonstrated that a sclerotic aorta contained bone marrow.

A comprehensive review of this issue published in Clinical Medicine Insights: Endocrinology and Diabetes guides clinicians through current evidence supporting the role of bisphosphonates in CVD. That clinical evidence includes:

• Bisphosphonates, which have a high affinity for calcium and hydroxyapatite, effectively address osteoporosis by targeting the main hydroxyapatite source, which is the skeleton.
• Bisphosphonates are also useful in diseases associated with osteoclast-mediated bone resorption, such as Paget’s disease, multiple myeloma, and osteolytic tumor metastasis.
• After the bone matrix forms, osteoclasts ingest bisphosphonates, which in turn induces apoptosis and leads to decreased bone resorption.
• Bisphosphonates have been found in calcified atherosclerotic plaques, and researchers have found etidronate and pamidronate in high concentrations within healthy aortas and mammary arteries.

It’s this last point that may explain the pharmacological agents’ possible inhibition of atherosclerosis, as bisphosphonates may have similar actions in bone and plaque. Therefore, bisphosphonates or similar agents represent a potential intervention to address CVD.

Etidronate is the most studied bisphosphonate vascular calcification inhibitor, and it’s considered the most potent. However, human research in this area has some limitations, including the fact that many of the studies are small or short studies, have a short duration of follow-up, contain subjects with confounding comorbidities, and lack well-structured placebo-controlled trials. As the research in the area of bisphosphonates grows, clinicians will want to follow it closely, especially since baby boomers are aging in large numbers and CVD remains a leading cause of death among that population.