We used the Egger’s test to quantitatively evaluate publication bias. All P-values were > 0.05, indicating that there was no publication bias. The quality of the included literature was evaluated by the NOS score, which were all above median level, indicating that the quality of the included literature was acceptable, and the results of the meta-analysis were relatively credible.
This meta-analysis involved 12 studies and a total of 12,395 subjects. The studies included two events (osteopenia and OP) and four indicators (TC, TG, HDL-C, and LDL-C). The larger number of subjects strived for a stable result. Some results in this meta-analysis were heterogeneous, so we performed subgroup analyses based on two factors. The first factor was the characteristics of the subjects, which may be due to the actions of hormone. Postmenopausal women are more prone to OP because of lack of estrogen protection. The other factor was whether or not take lipid-lowering drugs, because it affects blood lipid levels. Even if subgroup analyses were conducted, some sources of heterogeneity were still not found, and we considered the possible reason was mixed effects of multiple confounding factors.
Trimpou et al. observed the necrosis of the femoral head under an electron microscope and found that the number and size of fat cells were significantly increased, suggesting that hypercholesterolemia is an independent risk factor for osteoporotic fractures. A recent meta-analysis, including 33 studies (16 cohort studies, 7 case-control studies, and 10 randomized controlled trials) showed that statins reduced the risk of total and hip fractures. The use of statins has been associated with an increase in total hip BMD and lumbar spine and was found to increase the expression of bone formation markers, such as osteocalcin.
The pathophysiological relationship between blood lipid levels and BMD remains unclear. Most studies report that eating a high-fat diet reduces bone strength, changes the microstructure of the cancellous bone compartment, and changes the bone marrow environment, and low-level inflammation may play a role in these processes. TC and its metabolites have been reported to affect the functional activity of osteoblasts in vitro and in vivo. Elevated serum lipids may cause bone blood vessels to accumulate in the subendothelial matrix and may inhibit the differentiation and mineralization of bone cells.
This study has some limitations. First, the overall heterogeneity of the meta-analysis results obtained in this study was large, and the source of heterogeneity according to subject characteristics or lipid-lowering drugs was not identified in some studies. Considering the number of included studies, the sources of heterogeneity may involve many aspects. Second, most of the participants included in this meta-analysis were postmenopausal women because there are limited studies on men. However, the male population is a group that needs our attention. We look forward to more individual studies on male OP to perform a future meta-analysis. Third, we included case-control studies with weaker levels of evidence. Long-term cohort studies are needed to determine the effects of elevated blood lipids on osteopenia, OP, and fractures.