Introduction:
Osteoporosis and cardiovascular disease (CVD) are associated with a high rate of morbidity, death, and disability. Earlier, these conditions were thought to be unrelated, and the occurrence of these conditions was ascribed to different age-related processes. However, growing biological and epidemiological data points to a connection between the two disorders that goes beyond simple aging. Epidemiologic research on the relationship between bone density and cardiovascular morbidity, mortality, and subclinical atherosclerosis is being conducted worldwide. Further, various pathways that link these two conditions are being studied.
What Is the Association Between Osteoporosis and Cardiovascular Disease (CVD)?
Globally, osteoporosis is a significant health issue that is linked to a higher risk of fractures and death. It has been proved that an independent risk factor for both cardiovascular disease (CVD) and mortality is vascular calcification. Significant progress in comprehending the pathophysiology of vascular calcification and osteoporosis suggests that these two processes have similar pathogenetic pathways.
Many factors are involved in bone and vascular metabolism, showing how these seemingly unrelated conditions interact. These factors include proteins (such as osteoprotegerin, matrix Gla protein, receptor activator of nuclear factor κB ligand, and cathepsins), parathyroid hormone, phosphate, oxidized lipids, and vitamins D and K.
Numerous clinical investigations have now validated the association between vascular calcification and osteoporosis and the heightened risk of cardiovascular disease in individuals with osteoporosis. The molecular similarities between vascular calcification and osteoporosis also indicate that there is an association between these disorders.
Osteoporosis and cardiovascular disease (CVD) are prevalent age-related ailments. Growing epidemiological and biological data points to a connection between the two illnesses. In both cross-sectional and longitudinal epidemiologic research, low bone mineral density (BMD) has been associated with higher cardiovascular morbidity, cardiovascular mortality, and subclinical markers of atherosclerosis.
What Are the Similarities Between Bone Mineralization and Atherosclerotic Calcification?
There are various interesting similarities between bone mineralization and atherosclerotic calcification. It is now understood that the calcification of artery tissue is a highly structured process governed by mechanisms akin to those engaged in bone mineralization rather than just a passive process of calcium phosphate precipitation or adsorption in end-stage atherosclerosis.
The mineral in atherosclerotic plaque calcium deposits is chemically extremely similar to hydroxyapatite crystals, which comprise the inorganic bone matrix. Similar to "extracellular matrix vesicles," which are secreted from chondrocytes and osteoblasts and are involved in initial bone mineralization, calcifiable vesicles were recovered from human atherosclerotic aortas, indicating that these may be involved in mineral deposition.
Numerous bone matrix proteins, including type I collagen, gla (gamma carboxyglutamate)-containing proteins like osteocalcin (bone-gla protein) and matrix-gla protein, bone morphogenetic protein (BMP)-2 and -4, osteopontin, osteonectin, and bone sialoprotein, were also demonstrated to be expressed in calcified plaques. In atherosclerotic plaques, osteogenic cells have been identified as calcifying vascular cells (CVCs). These are recognized as vascular smooth muscle cells (VSMC) capable of differentiating into osteoblasts.
These cells express osteoblast genes, which are required for the creation of bones when they are activated by BMP-2 and BMP-4, such as:
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Alkaline phosphatase.
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Collagen I.
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Osteocalcin.
Plaques also revealed the presence of other cells related to bone metabolism, like hematopoietic bone marrow cells, chondrocyte-like cells, and osteoclast-like cells.
What Are the Common Risk Factors?
A theory suggests that the co-occurrence of osteoporosis and cardiovascular disease (CVD) results from common etiological factors such as physical activity, smoking, alcohol consumption, menopause, and hypertension. These factors can act together to either help or inhibit atherosclerosis and bone demineralization. This can explain some of the correlation between the two conditions. Even after adjusting for some of these risk factors, the association between osteoporosis and CVD was observed in numerous epidemiologic studies.
What Are the Common Genetic Factors?
The atherogenesis and bone loss processes have been linked to the genes for osteoprotegerin, matrix-gla protein, and apolipoprotein E (ApoE). It was discovered that mice deficient in the osteoprotegerin gene experienced early-onset osteoporosis and aortic and renal artery calcification. Similarly, animals deficient in the matrix gla protein gene showed osteopenia, fractures, and vascular calcification. The ApoE genotype was linked to atherosclerosis in patients with end-stage renal disease. Further, the ApoE4 gene has been linked to lower bone mineral density and an increased risk of fractures.
The link between osteoporosis and CVD needs to be confirmed by longer-term research. More research is essential to determine whether racial disparities exist in this connection. It is important to enquire about the relationship between bone loss and the development of vascular calcification. Early and prompt identification of patients at high risk of developing CVD and osteoporosis can be possible through a subclinical assessment of the condition and vice versa. Clarifying the shared processes underlying the relationship between osteoporosis and CVD is essential for future research. Once these pathways are understood, it will be possible to use shared preventive and treatment approaches focused on both illnesses.
Two of the leading causes of morbidity, death, and disability are CVD and osteoporosis. With age, both diseases worsen. These two situations were once considered unconnected, and their coexistence was attributed to separate age-related processes. Apart from age and common risk factors, a growing corpus of molecular and epidemiological research has recently supported an association between these two diseases.
Their pathogenesis is believed to be related to shared molecular, cellular, and biochemical pathways. Understanding the relationship between the two disorders and the mechanisms underlying their advancement might lead to the development of new paradigms for the prevention and treatment of osteoporosis and cardiovascular disease. Comprehending the biological connections could pave the way for dual-purpose preventative and therapeutic approaches to diminishing bone loss and its advancement.
Conclusion:
The RANKL–RANK–OPG pathway, MGP, vitamin K, and bone morphogenetic proteins are among the pathogenetic pathways that osteoporosis and vascular calcification have in common. Vascular calcification is more prevalent in osteoporosis patients than in people with average bone mineral density. Clinical data indicates that vascular calcification is linked to an elevated risk of fracture, and osteoporosis is linked to cardiovascular events and higher mortality. Cardiovascular and/or cardiac calcification in individuals with osteoporosis can be readily identified with basic screening procedures like thoracic and abdominal radiography or cardiac and carotid artery ultrasound.
