Lipid metabolism within the bone micro-environment is closely associated with bone metabolism in physiological and pathophysiological stages

Abstract

Recent advances in society have resulted in the emergence of both hyperlipidemia and obesity as life-threatening conditions in people with implications for various types of diseases, such as cardiovascular diseases and cancer. This is further complicated by a global rise in the aging population, especially menopausal women, who mostly suffer from overweight and bone loss simultaneously. Interestingly, clinical observations in these women suggest that osteoarthritis may be linked to a higher body mass index (BMI), which has led many to believe that there may be some degree of bone dysfunction associated with conditions such as obesity. It is also common practice in many outpatient settings to encourage patients to control their BMI and lose weight in an attempt to mitigate mechanical stress and thus reduce bone pain and joint dysfunction. Together, studies show that bone is not only a mechanical organ but also a critical component of metabolism, and various endocrine functions, such as calcium metabolism. Numerous studies have demonstrated a relationship between metabolic dysfunction in bone and abnormal lipid metabolism. Previous studies have also regarded obesity as a metabolic disorder. However, the relationship between lipid metabolism and bone metabolism has not been fully elucidated. In this narrative review, the data describing the close relationship between bone and lipid metabolism was summarized and the impact on both the normal physiology and pathophysiology of these tissues was discussed at both the molecular and cellular levels.

Do bisphosphonates and RANKL inhibitors alter the progression of coronary artery calcification? A systematic review and meta-analysis protocol

“…Their introduction to the pharmacological sphere has considerably reduced the incidence of pathological fractures and consequent rates of disability in patients with osteoporosis. Novel evidence suggests that there may be a role for their use in reducing the progression of CAD via their effects on atheroma formation 8 9. Bisphosphonates have been shown to inhibit the progression of ectopic calcification through inhibitory action on the crucial regulatory enzyme, farnesyl pyrophosphate synthase, in the mevalonic acid pathway, which is implicated in both bone and lipid metabolism 8 9.…”

“…Novel evidence suggests that there may be a role for their use in reducing the progression of CAD via their effects on atheroma formation 8 9. Bisphosphonates have been shown to inhibit the progression of ectopic calcification through inhibitory action on the crucial regulatory enzyme, farnesyl pyrophosphate synthase, in the mevalonic acid pathway, which is implicated in both bone and lipid metabolism 8 9. RANKL inhibitors interfere with the glycoprotein, osteoprotegerin (OPG) and other signalling pathways, again involved in lipid metabolism.…”

Bone Marrow Adiposity Alterations in Type 2 Diabetes Are Sex-Specific and Associated with Serum Lipid Levels

“…(28)(29)(30) Therefore, high cholesterol, in particular high LDL, can cause imbalance in the regulation of bone formation and resorption, resulting in bone quality decrease. (31,32) While no previous data exist on the relationship between serum lipid levels and marrow adiposity in humans with T2D, Slade et al reported a positive association between serum cholesterol level and marrow adiposity in humans with T1D. (22) This correlation has also been documented in people without diabetes.…”

Lipidomics Profiling of Patients with Low Bone Mineral Density (LBMD)

“…Some studies in the literature have examined the molecular mechanisms correlated with cholesterol-mediated bone deterioration (reviewed in [ 15 ]). High total cholesterol levels are negatively associated with BMD, while treatment with cholesterol-lowering drugs (statins) promotes bone production and thus enhances BMD [ 22 , 23 ]. Clinical studies investigating the changes in lipid metabolism and the levels of lipid molecules associated with LBMD in humans are limited.…”