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Article: Positive effects of low LDL-C and statins on bone mineral density: an integrated epidemiological observation analysis and Mendelian Randomization study
Title | Positive effects of low LDL-C and statins on bone mineral density: an integrated epidemiological observation analysis and Mendelian Randomization study |
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Authors | |
Keywords | LDL-C statins bone mineral density fracture coronary artery disease |
Issue Date | 2020 |
Publisher | Oxford University Press. The Journal's web site is located at http://ije.oxfordjournals.org/ |
Citation | International Journal of Epidemiology, 2020, v. 49 n. 4, p. 1221-1235 How to Cite? |
Abstract | BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is suggested to play a role in osteoporosis but its association with bone metabolism remains unclear. Effects of LDL-C-lowering drugs on bone are also controversial. We aim to determine whether LDL-C is linked causally to bone mineral density (BMD) and assess the effects of LDL-C-lowering drugs on BMD. METHODS: Association between blood lipid levels and BMD was examined by epidemiological observation analyses in a US representative cohort NHANES III (n = 3638) and the Hong Kong Osteoporosis Study (HKOS; n = 1128). Two-sample Mendelian randomization (MR), employing genetic data from a large-scale genome-wide association study (GWAS) of blood lipids (n = 188 577), total body BMD (TB-BMD) (n = 66 628) and estimated BMD (eBMD) (n= 142 487), was performed to infer causality between LDL-C and BMD. Genetic proxies for LDL-C-lowering drugs were used to examine the drugs' effects on BMD. RESULTS: In the NHANES III cohort, each standard deviation (SD) decrease in LDL-C was associated with a 0.045 SD increase in femoral neck BMD (95% CI: 0.009 - 0.081; P = 0.015). A similar increase in BMD was observed in the HKOS at femoral neck and lumbar spine. In MR analysis, a decrease in genetically predicted LDL-C was associated with an increase in TB-BMD {estimate per SD decrease, 0.038 [95% confidence interval (CI): 0.002 - 0.074]; P = 0.038} and eBMD [0.076 (0.042 - 0.111); P = 1.20x10-5]. Reduction in TB-BMD was causally associated with increased LDL-C [0.035 (0.033 - 0.066); P = 0.034]. Statins' LDL-C-lowering proxies were associated with increased TB-BMD [0.18 (0.044 - 0.316); P = 9.600x10-3] and eBMD [0.143 (0.062 - 0.223); P = 5.165x10-4]. CONCLUSIONS: Negative causal association exists between LDL-C level and BMD. Statins' LDL-C-lowering effect increases BMD, suggesting their protective effect on bone. |
Persistent Identifier | http://hdl.handle.net/10722/275099 |
ISSN | 2023 Impact Factor: 6.4 2023 SCImago Journal Rankings: 2.663 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Li, GHY | - |
dc.contributor.author | Cheung, CL | - |
dc.contributor.author | Au, PCM | - |
dc.contributor.author | Tan, KCB | - |
dc.contributor.author | Wong, ICK | - |
dc.contributor.author | Sham, PC | - |
dc.date.accessioned | 2019-09-10T02:35:27Z | - |
dc.date.available | 2019-09-10T02:35:27Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | International Journal of Epidemiology, 2020, v. 49 n. 4, p. 1221-1235 | - |
dc.identifier.issn | 0300-5771 | - |
dc.identifier.uri | http://hdl.handle.net/10722/275099 | - |
dc.description.abstract | BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is suggested to play a role in osteoporosis but its association with bone metabolism remains unclear. Effects of LDL-C-lowering drugs on bone are also controversial. We aim to determine whether LDL-C is linked causally to bone mineral density (BMD) and assess the effects of LDL-C-lowering drugs on BMD. METHODS: Association between blood lipid levels and BMD was examined by epidemiological observation analyses in a US representative cohort NHANES III (n = 3638) and the Hong Kong Osteoporosis Study (HKOS; n = 1128). Two-sample Mendelian randomization (MR), employing genetic data from a large-scale genome-wide association study (GWAS) of blood lipids (n = 188 577), total body BMD (TB-BMD) (n = 66 628) and estimated BMD (eBMD) (n= 142 487), was performed to infer causality between LDL-C and BMD. Genetic proxies for LDL-C-lowering drugs were used to examine the drugs' effects on BMD. RESULTS: In the NHANES III cohort, each standard deviation (SD) decrease in LDL-C was associated with a 0.045 SD increase in femoral neck BMD (95% CI: 0.009 - 0.081; P = 0.015). A similar increase in BMD was observed in the HKOS at femoral neck and lumbar spine. In MR analysis, a decrease in genetically predicted LDL-C was associated with an increase in TB-BMD {estimate per SD decrease, 0.038 [95% confidence interval (CI): 0.002 - 0.074]; P = 0.038} and eBMD [0.076 (0.042 - 0.111); P = 1.20x10-5]. Reduction in TB-BMD was causally associated with increased LDL-C [0.035 (0.033 - 0.066); P = 0.034]. Statins' LDL-C-lowering proxies were associated with increased TB-BMD [0.18 (0.044 - 0.316); P = 9.600x10-3] and eBMD [0.143 (0.062 - 0.223); P = 5.165x10-4]. CONCLUSIONS: Negative causal association exists between LDL-C level and BMD. Statins' LDL-C-lowering effect increases BMD, suggesting their protective effect on bone. | - |
dc.language | eng | - |
dc.publisher | Oxford University Press. The Journal's web site is located at http://ije.oxfordjournals.org/ | - |
dc.relation.ispartof | International Journal of Epidemiology | - |
dc.rights | This is a pre-copy-editing, author-produced PDF of an article accepted for publication in International Journal of Epidemiology following peer review. The definitive publisher-authenticated version International Journal of Epidemiology, 2020, v. 49 n. 4, p. 1221–1235 is available online at: https://academic.oup.com/ije/article-abstract/49/4/1221/5532119?redirectedFrom=fulltext | - |
dc.subject | LDL-C | - |
dc.subject | statins | - |
dc.subject | bone mineral density | - |
dc.subject | fracture | - |
dc.subject | coronary artery disease | - |
dc.title | Positive effects of low LDL-C and statins on bone mineral density: an integrated epidemiological observation analysis and Mendelian Randomization study | - |
dc.type | Article | - |
dc.identifier.email | Li, GHY: gloriali@hku.hk | - |
dc.identifier.email | Cheung, CL: lung1212@hku.hk | - |
dc.identifier.email | Au, PCM: philipa@hku.hk | - |
dc.identifier.email | Tan, KCB: kcbtan@hkucc.hku.hk | - |
dc.identifier.email | Wong, ICK: wongick@hku.hk | - |
dc.identifier.email | Sham, PC: pcsham@hku.hk | - |
dc.identifier.authority | Cheung, CL=rp01749 | - |
dc.identifier.authority | Tan, KCB=rp00402 | - |
dc.identifier.authority | Wong, ICK=rp01480 | - |
dc.identifier.authority | Sham, PC=rp00459 | - |
dc.description.nature | postprint | - |
dc.identifier.doi | 10.1093/ije/dyz145 | - |
dc.identifier.scopus | eid_2-s2.0-85096152266 | - |
dc.identifier.hkuros | 304055 | - |
dc.identifier.volume | 49 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 1221 | - |
dc.identifier.epage | 1235 | - |
dc.identifier.isi | WOS:000593363100021 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 0300-5771 | - |