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.

Background As the incidence of secretory osteoporosis has increased, bone loss, osteoporosis and their relationships with thyroid-stimulating hormone (TSH) have received increased attention. In this study, the role of TSH in bone metabolism and its possible underlying mechanisms were investigated. Methods We analyzed the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH and the bone mineral density (BMD) levels of 114 men with normal thyroid function. In addition, osteoblasts from rat calvarial samples were treated with different doses of TSH for different lengths of time. The related gene and protein expression levels were investigated. Results A comparison of the BMD between the high-level and low-level serum TSH groups showed that the TSH serum concentration was positively correlated with BMD. TSH at concentrations of 10 mU/mL and 100 mU/mL significantly increased the mRNA levels of ALP, COI1 and Runx2 compared with those of the control (P < 0.05, P < 0.01). Bone morphogenetic protein (BMP)2 activity was enhanced with both increased TSH concentration and increased time. The protein levels of Runx2 and osterix were increased in a dose-dependent manner. Conclusions The circulating concentrations of TSH and BMD were positively correlated with normal thyroid function in males. TSH promoted osteoblast proliferation and differentiation in rat primary osteoblasts.

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