A conceptual model of a pathway from osteoporosis to atherosclerosis: A scoping review

To address the evidence for shared biologic mechanisms between atherosclerotic cardiovascular disease and osteoporosis.

A scoping review was carried out that scanned 6285 manuscripts from 2025 to 1990 in five databases, yielding 742 relevant papers, from which 64 provided mechanistic evidence supporting the existence of a direct relationship. Papers that discussed other aspects of cardiovascular disease were not included.

From these papers, clinical, animal, and in vitro studies, we constructed a conceptual model determined by conditions resulting from osteoporosis ultimately resulting in atherosclerotic calcifications and the reverse. We describe how estrogen deficiency leads to hyperlipidemia, consequent inflammation and oxidative stress, liberation of calcium and phosphate from resorbing bone with trapping of both minerals in the circulation, reinforcement by calcium and phosphate of the inflammatory process, and the consequent effect on arteries. We also examine the effect of vascular calcification on subsequent bone loss and the clinical implications of this conceptual model both for the current definition of osteoporosis and for methods of screening and prevention of incipient cardiovascular disease in patients with osteoporosis and for screening and treatment of patients with atherosclerotic cardiovascular disease who may have subclinical osteoporosis.

Evidence exists supporting biological pathways that can transition from osteoporotic bone loss to atherosclerotic vascular calcification. High bone resorption appears to be a factor in the development of atherosclerotic vascular calcification. These findings provide a conceptual framework to view both conditions. However, more work is needed to better define these pathways and their relative importance.