Hypercholesterolaemia increases the risk of high‑turnover osteoporosis in men

Abstract

As the incidence of osteoporosis (OP) and hypercholesterolaemia in men has increased, male OP has drawn more attention from clinicians worldwide. The present study sought to investigate the effects of cholesterol on male bone. Between July 2015 and October 2015, 216 men (aged ≥18 years) were recruited for this cross-sectional study. To test our clinical hypothesis, we designed two male animal models: Exogenous hypercholesterolaemia induced by a high-cholesterol diet (HCD) and endogenous hypercholesterolaemia induced by apolipoprotein E (ApoE) knockout. Finally, the direct effects of cholesterol on osteoblasts were observed in cell experiments. In our clinical studies, men with hypercholesterolaemia displayed a lower bone mineral density (BMD) and increased beta collagen cross-linking (beta-CTX) and type I anterior collagen amino terminal peptide (PINP) levels compared to those of the control subjects. Serum cholesterol levels were a significant independent predictor of BMD, beta-CTX and PINP and were negatively correlated with BMD and positively correlated with beta-CTX and PINP levels. Our animal experimental results validated our clinical results, as they also indicated that hypercholesterolaemia damages bone microstructure and reduces bone strength. Cholesterol directly increased osteoblast functional gene expression in vitro . Hypercholesterolaemia increases the risk of high-turnover osteoporosis in men at least in part by excessively promoting the activity of the remodelling pathway. In addition, hypercholesterolaemia damages the bone microstructure, resulting in osteopenia or OP and reduced bone strength, leading to a higher risk of fracture in men. We emphasize the importance of preventing and treating hypercholesterolaemia as well as monitoring bone metabolic markers and BMD in men with hypercholesterolemia for the effective prevention of bone loss and subsequent fracture. In addition, our findings provide a theoretical basis for the development of treatments for high cholesterol-induced osteoporosis in men.

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis

“…A retrospective study has been shown that dyslipidemia in postmenopausal women is positively associated with OP progression [ 5 ]. Furthermore, hypercholesterolemia or high-cholesterol diets have been reported to reduce bone strength and enhance the potential risks of bone fracture and OP [ 6 ]. Excessive cholesterol in the body may cause OP [ 7 ].…”

Recent perspectives on the association between osteonecrosis and bone mineral density decline in childhood acute lymphoblastic leukemia

“…In addition, especially PEG-asparaginase leads to hyperlipidemia, which is associated with osteonecrosis in children with ALL 29 . The association between hyperlipidemia and low BMD has not been established in this population, but, interestingly, studies in the general adult population do show such an adverse effect 30 , 31 . High-dose methotrexate may additionally modify the risk of osteonecrosis and BMD decline due to inhibition of bone formation and mineralization 6 , 32 , 33 , although it has not been identified as an independent risk factor for either toxicity in children with cancer.…”

Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway

“… 2018 ), and BGP maintains a normal rate of bone calcification and inhibits the rate of cartilage mineralisation, which is an indicator of osteoblast activity (Zhou et al. 2019 ). In the current study, AU treatment increased the serum concentrations of BMP-2, BGP, BMPR-2 and COL I in OP mice and increased the expression levels of OPG, OCN and COL I in RANKL-exposed RAW264.7 cells.…”