Both osteoporosis and cardiovascular disease (CVD) are major public health problems leading to an increased morbidity and mortality rate. Impaired mineral metabolism appears to be associated with bone disease and also with vascular calcification. Many traditional biochemical markers of bone remodeling retain significance for atherosclerosis, CV risk, and vascular calcification. This chapter highlights the available literature on pathophysiological similarities between osteoporosis and CVD and presents an overview of the available evidence that supports the interaction between these conditions. Many common pathogenic factors have been proposed to promote atherogenesis and osteoporosis by acting on both vascular and bone cells. Cathepsin K (CatK) initially considered to be selectively expressed in bone, is the major protease of osteoclasts, responsible for bone resorption, with proteolytic activities against several ECM components. Tartrate‐resistant acid phosphatase 5b (TRACP5b) is a proteolytically processed isoform produced by osteoclasts, and represents a sensitive marker of bone resorption.