T2D and Osteoporosis Risk: A Mendelian Randomisation Study | [Journal of the College of Physicians and Surgeons Pakistan • 2025]

Author(s):

1. Zhenming Zeng: Department of Rehabilitation, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,China

2. Zhenzhen Wang: Department of Rehabilitation, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,China

3. Xiahai Zheng: Department of Rehabilitation, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,China

4. Tao Jiang: Department of Orthopaedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine,Guangzhou,China

5. Min Shao: Department of Rehabilitation, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,China

6. Yong Lian: Department of Orthopaedics, Third School of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine,Guangzhou,China

Abstract:

To investigate the causal e ect of Type-II Diabetes (T2D) on osteoporosis (OP) risk using a two-example Mendelian randomisation (MR). Study Design: Descriptive study. Place and Duration of the Study:Third School of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China, from February to July 2024. Methodology: The data of the whole gene association study (GWAS) were gathered from two separate databases and the same East Asia descent, including 433,540 genetic variants in T2D and 212,453 genetic variants in osteoporosis. These genetic variants were used as instrumental variables, subsequently, these variables were analysed by several methods, including inverse variance weighted (IVW)random e ects, MR-Egger regression, and weighted median estimator (WM). Results: The outcomes indicated that a potential causal association existed between T2D and OP in the primary MR analysis (IVW: Odds ratio (OR) = 1.0934, 95% con dence interval (95% CI): 0.8735-0.9643, p = 0.0007). Meanwhile, the secondary MR also revealed that T2D was causally associated with OP (MR-Egger: OR = 1.1142, 95% CI: 0.9511-0.9966, p = 0.0004, and WME: OR = 1.1422, 95% CI: 0.8611-0.9666, p = 0.0004). The accuracy and robustness of the above results were con rmed using sensitivity tests. Conclusion: A causal relationship was found between T2D and OP, which also revealed that T2D increased the risk of OP.

Page(s): 447-451

DOI: 10.29271/jcpsp.2025.04.447

Published: Journal: Journal of the College of Physicians and Surgeons Pakistan, Volume: 35, Issue: 04, Year: 2025

Keywords:

Osteoporosis , TypeII diabetes , Causal inference , Mendelian randomisation

References:

[1] Snyder S. .2024 .Postmenopausal osteoporosis. N Engl J Med, 10(7) : 675-6.

[2] Handel MN,Cardoso I,von Bulow C,Rohde JF,Ussing A,Nielsen SM .2023 .Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. BMJ, 10 : .

[3] Sheu A,Green eld JR,White CP,Center JR .2022 .Assessment and treatment of osteoporosis and fractures in type 2 diabetes. Trends Endocrinol Metab, 02(5) : 333-44.

[4] LeBo MS,Greenspan SL,Insogna KL,Lewiecki EM,Saag KG,Singer AJ .2022 .The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int, 10(10) : 2049-102.

[5] Tang F,Wang S,Zhao H,Xia D,Dong X .2023 .Mendelian randomisation analysis does not reveal a causal in uence of mental diseases on osteoporosis. Front Endocrinol (Lausanne), 1125427 : 1125427.

[6] Camacho PM,Petak SM,Binkley N,Diab DL,Eldeiry LS,Farooki A .2020 .American association of clinical endocrinologists/American college of endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update. Endocr Pract, 10(Suppl 1) : 1-46.

[7] Ali D,Tencerova M,Figeac F,Kassem M,Jafari A .2022 .The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity. Front Endocrinol (Lausanne), 981487 : 981487.

[8] Sun H,Saeedi P,Karuranga S,Pinkepank M,Ogurtsova K,Duncan BB . .Erratum to IDF diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045 [Diabetes Res. Clin. Pract, : .

[9] .2023 .. Diabetes Res Clin Pract, 110945 : 110945.

[10] Gagnon E,Mitchell PL,Manikpurage HD,Abner E,Taba N,Esko T .2023 .Impact of the gut microbiota and associated metabolites on cardiometabolic traits, chronic diseases and human longevity: A mendelian randomisation study. J Transl Med, 10(1) : 60.

[11] Wu Y,Qian Q,Liu Q,Wang R,Pu X,Li Y .2024 .Osteoporosis and primary biliary cholangitis: A trans-ethnic mendelian randomisation analysis. Clin Rev Allergy Immunol, 10(2) : 138-48.

[12] Kain J,Owen KA,Marion MC,Langefeld CD,Grammer AC,Lipsky PE .2022 .Mendelian randomisation and pathway analysis demonstrate shared genetic associations between lupus and coronary artery disease. Cell Rep Med, 100805(11) : 100805.

[13] Yuan S,Xu F,Li X,Chen J,Zheng J,Mantzoros CS .2023 .Plasma proteins and onset of type 2 diabetes and diabetic complications: Proteome-wide mendelian randomisation and colocalization analyses. Cell Rep Med, 101174(9) : 101174.

[14] Hofbauer LC,Busse B,Eastell R,Ferrari S,Frost M,Muller R .2022 .Bone fragility in diabetes: Novel concepts and clinical implications. Lancet Diabetes Endocrinol, 8587(21) : 00347-8.

[15] Minisola S,Arnold A,Belaya Z,Brandi ML,Clarke BL,Hannan FM .2022 .pathophysiology, and genetics of primary hyperparathyroidism. J Bone Miner Res, 10(11) : 2315-29.

[16] Zarnowski A,Jankowski M,Gujski M. .2022 .Public awareness of diet-related diseases and dietary risk factors: A 2022 nationwide cross-sectional survey among adults in poland. Nutrients, 10(16) : 3285.

[17] Walker MD,Shane E. .2023 .Postmenopausal osteoporosis. N Engl J Med, 10(21) : 1979-91.

[18] Laurent MR,Goemaere S,Verroken C,Bergmann P,Body JJ,Bruyere O .2022 .Prevention and treatment of glucocorticoid-induced osteoporosis in adults: Consensus recommendations from the belgian bone club. Front Endocrinol (Lausanne), 908727 : 908727.

[19] Skrivankova VW,Richmond RC,Woolf BAR,Davies NM,Swanson SA,VanderWeele TJ .2021 .Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): Explanation and elaboration. BMJ, 10 : .

[20] Skrivankova VW,Richmond RC,Woolf BAR,Yarmolinsky J,Davies NM,Swanson SA .2021 .Strengthening the reporting of observational studies in epidemiology using mendelian randomisation: The STROBE-MR statement. JAMA, 18236(16) : 1614-21.

Citations

Downloads

Views