دورية أكاديمية
أعرض في EDS

The Causal Relationship between PCSK9 Inhibitors and Osteoporosis Based on Drug-Targeted Mendelian Combined Mediation Analysis.

التفاصيل البيبلوغرافية
العنوان: The Causal Relationship between PCSK9 Inhibitors and Osteoporosis Based on Drug-Targeted Mendelian Combined Mediation Analysis.
المؤلفون: Zhang N; Department of Laboratory Medicine, Peoples Hospital of Deyang City, No 173, the First Section of North Taishan Road, Deyang, 618000, China. znd1984@126.com., Ji C; Department of Laboratory Medicine, Peoples Hospital of Deyang City, No 173, the First Section of North Taishan Road, Deyang, 618000, China., Liu L; Department of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China., Ye E; Department of Laboratory Medicine, Peoples Hospital of Deyang City, No 173, the First Section of North Taishan Road, Deyang, 618000, China., Yuan C; Department of Laboratory Medicine, Peoples Hospital of Deyang City, No 173, the First Section of North Taishan Road, Deyang, 618000, China.
المصدر: Calcified tissue international [Calcif Tissue Int] 2024 Jul; Vol. 115 (1), pp. 53-62. Date of Electronic Publication: 2024 May 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Verlag Country of Publication: United States NLM ID: 7905481 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0827 (Electronic) Linking ISSN: 0171967X NLM ISO Abbreviation: Calcif Tissue Int Subsets: MEDLINE
أسماء مطبوعة: Publication: New York Ny : Springer Verlag
Original Publication: Berlin, New York, Springer International.
مواضيع طبية MeSH: Osteoporosis*/epidemiology , Mendelian Randomization Analysis* , PCSK9 Inhibitors* , Bone Density*/drug effects, Humans ; Middle Aged ; Female ; Male ; Adult ; Mediation Analysis ; Cholesterol, LDL/blood ; Proprotein Convertase 9
مستخلص: PCSK9 inhibitors have been shown to lower serum low density lipoprotein cholesterol (LDL-C) levels and are considered integral in the treatment of cardiovascular diseases. However, the potential association between PCSK9 inhibitors and osteoporosis is unclear now. In this study, drug-targeted mendelian randomization (MR) was utilized in conjunction with mediation analysis including bone mineral density (BMD), total 25-hydroxyvitamin D (T25(OH)D) levels and calcium supplementation to investigate the causal relationship between PCSK9 inhibitors and osteoporosis. The LDL-C level was chosen as the exposure variable in a sample size of 173,082 individuals. We conducted a MR analysis on the relationship between PCSK9 inhibitors and osteoporosis, elucidating the mediators involved. Utilizing the inverse variance weighted (IVW) method, we found the risk of osteoporosis was reduced by 0.6% in those who used PCSK9 inhibitors compared with non-users (OR: 0.994, 95%CI: 0.991-0.998, P < 0.001). In people aged 30-45 years, the risk of low BMD was 1.176 times higher among PCSK9 inhibitor users compared to non-users (OR: 1.176, 95%CI: 1.017-1.336, P = 0.045). Conversely, people aged 45-60 years who used PCSK9 inhibitors had a 14.9% lower risk of low BMD compared to non-users (OR: 0.851, 95%CI: 0.732-0.968, P = 0.007). Mediation analysis revealed that 43.33% of the impact of PCSK9 inhibitors on osteoporosis was mediated through BMD levels, with the remaining 56.67% being a direct effect. Effects of PCSK9 inhibitors on BMD levels varied in different ages. In addition, the risk of high serum T25(OH)D levels were 1.091 times among PCSK9 inhibitor users compared to non-users (OR: 1.091, 95%CI: 1.065-1.112, P < 0.001), providing valuable insights for clinicians.
(© 2024. The Author(s).)
References: Aging Cell. 2018 Dec;17(6):e12828. (PMID: 30256507)
Scand J Clin Lab Invest. 2014 Apr;74(3):177-83. (PMID: 24383929)
Genet Epidemiol. 2023 Jun;47(4):314-331. (PMID: 37036286)
Nat Genet. 2013 Nov;45(11):1274-1283. (PMID: 24097068)
Yonsei Med J. 2015 Sep;56(5):1251-7. (PMID: 26256967)
Genes (Basel). 2024 Jan 21;15(1):. (PMID: 38275613)
Front Cell Dev Biol. 2021 Mar 29;9:645593. (PMID: 33855023)
N Engl J Med. 2014 Sep 11;371(11):993-1004. (PMID: 25176015)
Indian Heart J. 2024 Mar-Apr;76(2):79-85. (PMID: 38342141)
Circ Cardiovasc Qual Outcomes. 2021 Jan;14(1):e005623. (PMID: 33397121)
PLoS Med. 2022 Dec 29;19(12):e1004141. (PMID: 36580444)
Int J Epidemiol. 2022 Jan 6;50(6):1995-2010. (PMID: 34999880)
Int J Epidemiol. 2017 Oct 5;47(1):29-35. (PMID: 29040602)
Int J Gen Med. 2022 Feb 28;15:2261-2270. (PMID: 35250302)
Nat Commun. 2020 Jun 26;11(1):3255. (PMID: 32591531)
Arch Gerontol Geriatr. 2018 Nov - Dec;79:8-12. (PMID: 30071402)
Genes Nutr. 2023 Sep 9;18(1):13. (PMID: 37689663)
Metab Syndr Relat Disord. 2015 Apr;13(3):99-101. (PMID: 25734961)
Kidney Int Suppl (2011). 2011 Sep;1(4):136-141. (PMID: 25018912)
Nat Commun. 2020 Apr 2;11(1):1647. (PMID: 32242144)
Allergy Asthma Immunol Res. 2011 Oct;3(4):251-5. (PMID: 21966605)
Front Immunol. 2023 Jan 04;13:1057253. (PMID: 36685511)
Int J Mol Sci. 2022 Feb 28;23(5):. (PMID: 35269841)
Lipids Health Dis. 2011 Feb 28;10:38. (PMID: 21352602)
N Engl J Med. 2015 Jun 18;372(25):2387-97. (PMID: 26039521)
Eur J Clin Invest. 2021 Apr;51(4):e13459. (PMID: 33236356)
Nat Rev Endocrinol. 2015 Sep;11(9):513-21. (PMID: 26032105)
Am J Hum Genet. 2018 Jan 4;102(1):88-102. (PMID: 29304378)
Expert Rev Cardiovasc Ther. 2018 Aug;16(8):567-578. (PMID: 29979908)
N Engl J Med. 2012 Mar 22;366(12):1108-18. (PMID: 22435370)
Nat Rev Rheumatol. 2015 Aug;11(8):462-74. (PMID: 25900210)
Osteoporos Int. 2017 Feb;28(2):447-462. (PMID: 27761590)
Expert Opin Biol Ther. 2017 May;17(5):633-643. (PMID: 28277798)
Clin Orthop Relat Res. 2011 Jul;469(7):1891-9. (PMID: 21431462)
Lancet Diabetes Endocrinol. 2021 Sep;9(9):606-621. (PMID: 34242583)
Neurologia (Engl Ed). 2019 Apr;34(3):198-203. (PMID: 28549755)
Front Cardiovasc Med. 2022 Sep 14;9:901786. (PMID: 36186975)
Curr Cardiol Rev. 2017;13(4):319-324. (PMID: 28925859)
Expert Rev Clin Immunol. 2022 Jan;18(1):67-74. (PMID: 34928185)
Hematology. 2013 Jan;18(1):20-5. (PMID: 22980447)
Int J Obes (Lond). 2022 Aug;46(8):1487-1492. (PMID: 35538205)
N Engl J Med. 2016 Sep 8;375(10):971-9. (PMID: 27602669)
Clin Chim Acta. 2010 Dec 14;411(23-24):1875-82. (PMID: 20816951)
Psychol Methods. 2015 Jun;20(2):193-203. (PMID: 25664380)
PLoS One. 2017 Jan 3;12(1):e0169122. (PMID: 28046015)
Liver Int. 2015 Oct;35(10):2294-300. (PMID: 25757956)
RSC Adv. 2019 Jun 12;9(32):18589-18598. (PMID: 35515248)
J Am Geriatr Soc. 2021 May;69(5):1388-1398. (PMID: 33624287)
Nutrients. 2020 Sep 30;12(10):. (PMID: 33007863)
Int J Mol Sci. 2019 Apr 28;20(9):. (PMID: 31035384)
J Bone Miner Res. 2020 Dec;35(12):2355-2362. (PMID: 32717113)
معلومات مُعتمدة: ZYTS130 Education Reform Project of Southwest Medical University
فهرسة مساهمة: Keywords: Drug-targeted mendelian randomization; Mediation analysis; Osteoporosis; PCSK9 inhibitors
المشرفين على المادة: 0 (PCSK9 Inhibitors)
EC 3.4.21.- (PCSK9 protein, human)
0 (Cholesterol, LDL)
EC 3.4.21.- (Proprotein Convertase 9)
تواريخ الأحداث: Date Created: 20240524 Date Completed: 20240605 Latest Revision: 20240608
رمز التحديث: 20240608
مُعرف محوري في PubMed: PMC11153280
DOI: 10.1007/s00223-024-01228-x
PMID: 38789568
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-0827
DOI:10.1007/s00223-024-01228-x