HDL cholesterol and bone mineral density: Is there a genetic link?

Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases.This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism.

► Correlation studies have not resolved the relationship between HDL and BMD. ► Studies in mice have shown that genetic loci for BMD and HDL co-map. ► Transgenic mouse models suggest that a single gene can affect both HDL and BMD. ► HDL interacts with both osteoblasts and osteoclasts. ► No direct evidence links bone back to the regulation of HDL levels.