Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein or lipoprotein (a) and bone health: a systematic review of observational studies and Mendelian randomization
Bibliographic record
Abstract
Cardiovascular calcification has been associated with osteoporosis and observational studies have linked lipids with bone and vascular mineralization suggesting a possible common link. However, the evidence that lipids associate with bone health is conflicting and the causal nature of this association remains unclear. Accordingly, we sought to (1) summarize the epidemiologic evidence for the association between total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG) or lipoprotein (a) (Lp(a)) with bone mineral density (BMD), osteoporosis or osteoporotic fractures by performing a systematic review of the literature; and (2) to provide evidence for a causal association, by performing a Mendelian randomization (MR) study of lipid-associated single nucleotide polymorphisms (SNPs) and BMD. We searched the Cochrane Library, Medline, and Embase from inception until December 15, 2014 for studies that assessed the association of lipids (LDL-C, T-C, HDL-C and Lp(a)) on bone mineral density, osteoporosis and osteoporotic fractures. We included observational studies; cohort, case-control and cross-sectional studies which included adults (age > 20 years). For Mendelian randomization (MR) analyses, we used summary level statistics from the GEFOS consortium, a large-scale genome-wide association of bone mineral density (BMD), to evaluate the effect of lipid SNPs on BMD. In our systematic review, we included 18 observational studies, comprising 29,326 participants (58% women; women mean age 59 years, men mean age 57 years). Among eligible studies, 11 studies reported an association between increasing T-C or LDL-C with reduced BMD whereas 7 studies reported no association or a protective relationship with higher T-C or LDL-C. The evidence for other lipids and BMD were even less consistent. We found that the quality of observational studies was highly variable with marked clinical and methodological heterogeneity which precluded quantitative meta-analysis. In MR analyses, genetic risk scores for LDL-C, HDL-C, TG and Lp(a) did not demonstrate a statistically significant association with BMD. In summary, the evidence from several observational studies for an association between cholesterol indices and bone mineral density/osteoporosis is inconsistent. Furthermore, our genetic analyses do not support a causal association and suggest that confounding and/or other biases may explain the conflicting observational results. Our work strongly suggests that lipids do not have a major impact in bone health.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.072 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.009 |
| Bibliometrics | 0.011 | 0.014 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".