High Cholesterol Deteriorates Bone Health: New Insights into Molecular Mechanisms

Abstract

Many epidemiological studies show a positive connection between cardiovascular diseases and risk of osteoporosis, suggesting a role of hyperlipidemia and/or hypercholesterolemia in regulating osteoporosis. The majority of the studies indicated a correlation between high cholesterol and high LDL-cholesterol level with low bone mineral density, a strong predictor of osteoporosis. Similarly, bone metastasis is a serious complication of cancer for patients. Several epidemiological and basic studies have established that high cholesterol is associated with increased cancer risk. Moreover, osteoporotic bone environment predisposes the cancer cells for metastatic growth in the bone microenvironment. This review focuses on how cholesterol and cholesterol-lowering drugs (statins) regulate the functions of bone residential osteoblast and osteoclast cells to augment or to prevent bone deterioration. Moreover, this study provides an insight into molecular mechanisms of cholesterol-mediated bone deterioration. It also proposes a potential mechanism by which cellular cholesterol boosts cancer-induced bone metastasis.

The Effect of Hypercholesterolemia on Cortical Bone Thickness of Wistar Rats (Rattus norvegicus)

“…On the other hand, hypercholesterolemia can induce cathepsin K of osteoclasts that are positively correlated with RANKL expression leading to increase osteoclastogenesis (Mandal 2015). Cathepsin K secreted by osteoclasts can resorb the bone and destruct the bone matrix which consists mostly of type 1 collagen (Now & Nandeesh 2012).…”

“…Besides, according to other studies, high cholesterol level can induce cathepsin K which directly increases RANKL production that subsequently binds to RANK receptor on the surface osteoclasts. Osteoclast activation induces osteoclastogenesis process which increases osteoclast production (Mandal 2015).…”

Preliminary evaluation of serum total cholesterol concentrations in dogs with osteosarcoma

“…2002, Luegmayr et al . 2004, Mandal 2015. Both LDL and HDL cholesterol concentrations have been correlated with bone mineral density values in post-menopausal women with osteoporosis (Yamaguchi et al .…”

“…2004 ). Numerous studies have been performed evaluating the role of both serum and cellular cholesterol concentrations on bone health via a variety of methodologies (cell culture cell lines, animal models as well as clinical samples) in human medicine (Mandal 2015 ). The findings of these studies revealed that: (1) elevated cholesterol concentrations may increase bone turnover (You et al .…”

“…2011 );and (3) the primary metabolite of cholesterol can result in increased bone resorption by decreasing osteoblast differentiation and enhancing osteoclastogenesis (Nelson et al . 2011, Mandal 2015. Research in cancer lipidomics is lacking in the veterinary field, with only a handful of papers describing preliminary evaluations in dogs with lymphoma and mammary tumours (Ogilvie et al .…”