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HDL cholesterol and bone mineral density: is there a genetic link?
1The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. cheryl.ackertb@jax.org
Insights
Researchers explored the link between cardiovascular disease and osteoporosis, finding that high-density lipoprotein cholesterol (HDL) and bone mineral density (BMD) may share underlying genetic causes. This discovery could lead to new treatments for both conditions.
Area of Science:
- Biomedical research
- Gerontology
- Metabolic and bone diseases
Background:
- Cardiovascular disease (CVD) and osteoporosis are prevalent in the elderly.
- Low high-density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are independent risk factors for CVD and osteoporosis, respectively.
- Existing correlation studies on HDL and BMD are limited by confounding variables.
Purpose of the Study:
- To investigate the potential shared genetic underpinnings of cardiovascular disease and osteoporosis.
- To clarify the relationship between serum HDL and BMD.
Main Methods:
- Review of existing correlation studies.
- Analysis of genetic loci mapping in mice.
- Examination of transgenic mouse models.
- In vitro studies on HDL interaction with osteoblasts and osteoclasts.
Main Results:
- Genetic loci for BMD and HDL levels co-map in mice.
- Transgenic mouse models show single genes can influence both HDL and BMD.
- HDL directly interacts with bone cells (osteoblasts and osteoclasts).
Conclusions:
- A genetic link likely exists between HDL regulation and BMD.
- Understanding this genetic relationship is crucial for managing the clinical link between CVD and osteoporosis.
- Further research is needed to explore bone's role in regulating HDL levels.
Abstract:
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.
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