{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:03:27Z","timestamp":1792267407446,"version":"4.4.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"publisher","award":["cstc2019jcyj-msxmX0836"],"award-info":[{"award-number":["cstc2019jcyj-msxmX0836"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"national natural science foundation of china","doi-asserted-by":"publisher","award":["81701382"],"award-info":[{"award-number":["81701382"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Calcif Tissue Int"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Observational studies suggest a link between depression and osteoporosis, but these may be subject to confounding and reverse causality. In this two-sample Mendelian randomization analysis, we included the large meta-analysis of genome-wide association studies for depression among 807,553 individuals (246,363 cases and 561,190 controls) of European descent, the large meta-analysis to identify genetic variants associated with femoral neck bone mineral density (FN-BMD), forearm BMD (FA-BMD) and lumbar spine BMD (LS-BMD) among 53,236 individuals of European ancestry, and the GWAS summary data of heel BMD (HE-BMD) and fracture among 426,824 individuals of European ancestry. The results revealed that genetic predisposition towards depression showed no causal effect on FA-BMD (beta-estimate: 0.091, 95% confidence interval [CI] \u2212\u00a00.088 to 0.269, SE:0.091, <jats:italic>P<\/jats:italic> value\u2009=\u20090.320), FN-BMD (beta-estimate: 0.066, 95% CI \u2212\u00a00.016 to 0.148, SE:0.042, <jats:italic>P<\/jats:italic> value\u2009=\u20090.113), LS-BMD (beta-estimate: 0.074, 95% CI \u2212\u00a00.029 to 0.177, SE:0.052, <jats:italic>P<\/jats:italic> value\u2009=\u20090.159), HE-BMD (beta-estimate: 0.009, 95% CI \u2212\u00a00.043 to 0.061, SE:0.027, <jats:italic>P<\/jats:italic> value\u2009=\u20090.727), or fracture (beta-estimate: 0.008, 95% CI \u2212\u00a00.071 to 0.087, SE:0.041, <jats:italic>P<\/jats:italic> value\u2009=\u20090.844). These results were also confirmed by multiple sensitivity analyses. Contrary to the findings of observational studies, our results do not reveal a causal role of depression in osteoporosis or fracture.<\/jats:p>","DOI":"10.1007\/s00223-021-00886-5","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T04:03:22Z","timestamp":1626235402000},"page":"675-684","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Depression and Osteoporosis: A Mendelian Randomization Study"],"prefix":"10.1007","volume":"109","author":[{"given":"Bin","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengxue","family":"Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsheng","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"886_CR1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k3225","author":"K Trajanoska","year":"2018","unstructured":"Trajanoska K, Morris JA, Oei L, Zheng HF, Evans DM, Kiel DP, Ohlsson C, Richards JB, Rivadeneira F (2018) Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study. BMJ. https:\/\/doi.org\/10.1136\/bmj.k3225","journal-title":"BMJ"},{"issue":"2","key":"886_CR2","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nrrheum.2009.260","volume":"6","author":"N Harvey","year":"2010","unstructured":"Harvey N, Dennison E, Cooper C (2010) Osteoporosis: impact on health and economics. Nat Rev Rheumatol 6(2):99\u2013105","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"886_CR3","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41588-018-0302-x","volume":"51","author":"JA Morris","year":"2019","unstructured":"Morris JA, Kemp JP, Youlten SE, Laurent L, Logan JG, Chai RC, Vulpescu NA, Forgetta V, Kleinman A, Mohanty ST, Sergio CM, Quinn J, Nguyen-Yamamoto L, Luco AL, Vijay J, Simon MM, Pramatarova A, Medina-Gomez C, Trajanoska K, Ghirardello EJ, Butterfield NC, Curry KF, Leitch VD, Sparkes PC, Adoum AT, Mannan NS, Komla-Ebri DSK, Pollard AS, Dewhurst HF, Hassall TAD, Beltejar MG, Adams DJ, Vaillancourt SM, Kaptoge S, Baldock P, Cooper C, Reeve J, Ntzani EE, Evangelou E, Ohlsson C, Karasik D, Rivadeneira F, Kiel DP, Tobias JH, Gregson CL, Harvey NC, Grundberg E, Goltzman D, Adams DJ, Lelliott CJ, Hinds DA, Ackert-Bicknell CL, Hsu YH, Maurano MT, Croucher PI, Williams GR, Bassett JHD, Evans DM, Richards JB (2019) An atlas of genetic influences on osteoporosis in humans and mice. Nat Genet 51(2):258\u2013266","journal-title":"Nat Genet"},{"issue":"10","key":"886_CR4","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1007\/s40618-019-01041-6","volume":"42","author":"J Liu","year":"2019","unstructured":"Liu J, Curtis EM, Cooper C, Harvey NC (2019) State of the art in osteoporosis risk assessment and treatment. J Endocrinol Invest 42(10):1149\u20131164","journal-title":"J Endocrinol Invest"},{"issue":"8","key":"886_CR5","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1056\/NEJMoa1916525","volume":"383","author":"DM Black","year":"2020","unstructured":"Black DM, Geiger EJ, Eastell R, Vittinghoff E, Li BH, Ryan DS, Dell RM, Adams AL (2020) Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates. N Engl J Med 383(8):743\u2013753","journal-title":"N Engl J Med"},{"issue":"3","key":"886_CR6","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1210\/clinem\/dgz162","volume":"105","author":"BZ Leder","year":"2020","unstructured":"Leder BZ, Mitlak B, Hu MY, Hattersley G, Bockman RS (2020) Effect of abaloparatide vs alendronate on fracture risk reduction in postmenopausal women With osteoporosis. J Clin Endocrinol Metab 105(3):938\u2013943","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"886_CR7","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41574-020-0339-7","volume":"16","author":"IR Reid","year":"2020","unstructured":"Reid IR (2020) A broader strategy for osteoporosis interventions. Nat Rev Endocrinol 16(6):333\u2013339","journal-title":"Nat Rev Endocrinol"},{"issue":"11","key":"886_CR8","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/S2213-8587(17)30188-2","volume":"5","author":"S Khosla","year":"2017","unstructured":"Khosla S, Hofbauer LC (2017) Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol 5(11):898\u2013907","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"10169","key":"886_CR9","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","volume":"393","author":"JE Compston","year":"2019","unstructured":"Compston JE, McClung MR, Leslie WD (2019) Osteoporosis. Lancet 393(10169):364\u2013376","journal-title":"Lancet"},{"issue":"8","key":"886_CR10","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/nrg3228","volume":"13","author":"JB Richards","year":"2012","unstructured":"Richards JB, Zheng HF, Spector TD (2012) Genetics of osteoporosis from genome-wide association studies: advances and challenges. Nat Rev Genet 13(8):576\u2013588","journal-title":"Nat Rev Genet"},{"key":"886_CR11","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.bone.2019.04.005","volume":"126","author":"K Trajanoska","year":"2019","unstructured":"Trajanoska K, Rivadeneira F (2019) The genetic architecture of osteoporosis and fracture risk. Bone 126:2\u201310","journal-title":"Bone"},{"issue":"2","key":"886_CR12","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41574-019-0282-7","volume":"16","author":"TL Yang","year":"2020","unstructured":"Yang TL, Shen H, Liu A, Dong SS, Zhang L, Deng FY, Zhao Q, Deng HW (2020) A road map for understanding molecular and genetic determinants of osteoporosis. Nat Rev Endocrinol 16(2):91\u2013103","journal-title":"Nat Rev Endocrinol"},{"issue":"3","key":"886_CR13","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41593-018-0326-7","volume":"22","author":"DM Howard","year":"2019","unstructured":"Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, Coleman JRI, Hagenaars SP, Ward J, Wigmore EM, Alloza C, Shen X, Barbu MC, Xu EY, Whalley HC, Marioni RE, Porteous DJ, Davies G, Deary IJ, Hemani G, Berger K, Teismann H, Rawal R, Arolt V, Baune BT, Dannlowski U, Domschke K, Tian C, Hinds DA, Trzaskowski M, Byrne EM, Ripke S, Smith DJ, Sullivan PF, Wray NR, Breen G, Lewis CM, McIntosh AM (2019) Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci 22(3):343\u2013352","journal-title":"Nat Neurosci"},{"issue":"1","key":"886_CR14","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3122\/jabfm.2011.01.100121","volume":"24","author":"RS Shim","year":"2011","unstructured":"Shim RS, Baltrus P, Ye J, Rust G (2011) Prevalence, treatment, and control of depressive symptoms in the United States: results from the National Health and Nutrition Examination Survey (NHANES), 2005\u20132008. JABFM 24(1):33\u201338","journal-title":"JABFM"},{"issue":"8","key":"886_CR15","doi-asserted-by":"publisher","first-page":"e00489","DOI":"10.1002\/brb3.489","volume":"6","author":"JU Schweiger","year":"2016","unstructured":"Schweiger JU, Schweiger U, H\u00fcppe M, Kahl KG, Greggersen W, Fassbinder E (2016) Bone density and depressive disorder: a meta-analysis. Brain Behav 6(8):e00489","journal-title":"Brain Behav"},{"issue":"4","key":"886_CR16","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1097\/PSY.0000000000000292","volume":"78","author":"B Stubbs","year":"2016","unstructured":"Stubbs B, Brefka S, Dallmeier D, Stubbs J, Vancampfort D, Denkinger MD (2016) Depression and reduced bone mineral density at the hip and lumbar spine: a comparative meta-analysis of studies in adults 60 years and older. Psychosom Med 78(4):492\u2013500","journal-title":"Psychosom Med"},{"issue":"8","key":"886_CR17","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1007\/s00198-009-0918-x","volume":"20","author":"Q Wu","year":"2009","unstructured":"Wu Q, Magnus JH, Liu J, Bencaz AF, Hentz JG (2009) Depression and low bone mineral density: a meta-analysis of epidemiologic studies. Osteoporos Int 20(8):1309\u20131320","journal-title":"Osteoporos Int"},{"issue":"5","key":"886_CR18","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.biopsych.2009.03.016","volume":"66","author":"R Yirmiya","year":"2009","unstructured":"Yirmiya R, Bab I (2009) Major depression is a risk factor for low bone mineral density: a meta-analysis. Biol Psychiat 66(5):423\u2013432","journal-title":"Biol Psychiat"},{"issue":"11","key":"886_CR19","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1002\/sim.6835","volume":"35","author":"S Burgess","year":"2016","unstructured":"Burgess S, Dudbridge F, Thompson SG (2016) Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods. Stat Med 35(11):1880\u20131906","journal-title":"Stat Med"},{"issue":"6","key":"886_CR20","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1002\/jbmr.2434","volume":"30","author":"N Dalbeth","year":"2015","unstructured":"Dalbeth N, Topless R, Flynn T, Cadzow M, Bolland MJ, Merriman TR (2015) Mendelian randomization analysis to examine for a causal effect of urate on bone mineral density. J Bone Miner Res 30(6):985\u2013991","journal-title":"J Bone Miner Res"},{"issue":"7499","key":"886_CR21","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1136\/bmj.330.7499.1076","volume":"330","author":"G Davey Smith","year":"2005","unstructured":"Davey Smith G, Ebrahim S (2005) What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ 330(7499):1076\u20131079","journal-title":"BMJ"},{"key":"886_CR22","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601","author":"NM Davies","year":"2018","unstructured":"Davies NM, Holmes MV, Davey Smith G (2018) Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. https:\/\/doi.org\/10.1136\/bmj.k601","journal-title":"BMJ"},{"issue":"7","key":"886_CR23","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/aje\/kwt084","volume":"178","author":"BL Pierce","year":"2013","unstructured":"Pierce BL, Burgess S (2013) Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol 178(7):1177\u20131184","journal-title":"Am J Epidemiol"},{"issue":"7","key":"886_CR24","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1007\/s10654-015-0011-z","volume":"30","author":"S Burgess","year":"2015","unstructured":"Burgess S, Scott RA, Timpson NJ, Davey Smith G, Thompson SG (2015) Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors. Eur J Epidemiol 30(7):543\u2013552","journal-title":"Eur J Epidemiol"},{"issue":"7571","key":"886_CR25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nature14878","volume":"526","author":"HF Zheng","year":"2015","unstructured":"Zheng HF, Forgetta V, Hsu YH, Estrada K, Rosello-Diez A, Leo PJ, Dahia CL, Park-Min KH, Tobias JH, Kooperberg C, Kleinman A, Styrkarsdottir U, Liu CT, Uggla C, Evans DS, Nielson CM, Walter K, Pettersson-Kymmer U, McCarthy S, Eriksson J, Kwan T, Jhamai M, Trajanoska K, Memari Y, Min J, Huang J, Danecek P, Wilmot B, Li R, Chou WC, Mokry LE, Moayyeri A, Claussnitzer M, Cheng CH, Cheung W, Medina-G\u00f3mez C, Ge B, Chen SH, Choi K, Oei L, Fraser J, Kraaij R, Hibbs MA, Gregson CL, Paquette D, Hofman A, Wibom C, Tranah GJ, Marshall M, Gardiner BB, Cremin K, Auer P, Hsu L, Ring S, Tung JY, Thorleifsson G, Enneman AW, van Schoor NM, de Groot LC, van der Velde N, Melin B, Kemp JP, Christiansen C, Sayers A, Zhou Y, Calderari S, van Rooij J, Carlson C, Peters U, Berlivet S, Dostie J, Uitterlinden AG, Williams SR, Farber C, Grinberg D, LaCroix AZ, Haessler J, Chasman DI, Giulianini F, Rose LM, Ridker PM, Eisman JA, Nguyen TV, Center JR, Nogues X, Garcia-Giralt N, Launer LL, Gudnason V, Mellstr\u00f6m D, Vandenput L, Amin N, van Duijn CM, Karlsson MK, Ljunggren \u00d6, Svensson O, Hallmans G, Rousseau F, Giroux S, Bussi\u00e8re J, Arp PP, Koromani F, Prince RL, Lewis JR, Langdahl BL, Hermann AP, Jensen JE, Kaptoge S, Khaw KT, Reeve J, Formosa MM, Xuereb-Anastasi A, \u00c5kesson K, McGuigan FE, Garg G, Olmos JM, Zarrabeitia MT, Riancho JA, Ralston SH, Alonso N, Jiang X, Goltzman D, Pastinen T, Grundberg E, Gauguier D, Orwoll ES, Karasik D, Davey-Smith G, Smith AV, Siggeirsdottir K, Harris TB, Zillikens MC, van Meurs JB, Thorsteinsdottir U, Maurano MT, Timpson NJ, Soranzo N, Durbin R, Wilson SG, Ntzani EE, Brown MA, Stefansson K, Hinds DA, Spector T, Cupples LA, Ohlsson C, Greenwood CM, Jackson RD, Rowe DW, Loomis CA, Evans DM, Ackert-Bicknell CL, Joyner AL, Duncan EL, Kiel DP, Rivadeneira F, Richards JB (2015) Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature 526(7571):112\u2013117","journal-title":"Nature"},{"issue":"2","key":"886_CR26","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1093\/ije\/dyv071","volume":"44","author":"AG Boef","year":"2015","unstructured":"Boef AG, Dekkers OM, le Cessie S (2015) Mendelian randomization studies: a review of the approaches used and the quality of reporting. Int J Epidemiol 44(2):496\u2013511","journal-title":"Int J Epidemiol"},{"issue":"3","key":"886_CR27","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/ije\/dyr036","volume":"40","author":"S Burgess","year":"2011","unstructured":"Burgess S, Thompson SG (2011) Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol 40(3):755\u2013764","journal-title":"Int J Epidemiol"},{"issue":"7414","key":"886_CR28","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JP Higgins","year":"2003","unstructured":"Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557\u2013560","journal-title":"BMJ"},{"issue":"11","key":"886_CR29","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1002\/sim.7221","volume":"36","author":"J Bowden","year":"2017","unstructured":"Bowden J, Del Greco MF, Minelli C, Davey Smith G, Sheehan N, Thompson J (2017) A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med 36(11):1783\u20131802","journal-title":"Stat Med"},{"issue":"5","key":"886_CR30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","volume":"32","author":"S Burgess","year":"2017","unstructured":"Burgess S, Thompson SG (2017) Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol 32(5):377\u2013389","journal-title":"Eur J Epidemiol"},{"issue":"5","key":"886_CR31","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","volume":"50","author":"M Verbanck","year":"2018","unstructured":"Verbanck M, Chen CY, Neale B, Do R (2018) Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet 50(5):693\u2013698","journal-title":"Nat Genet"},{"issue":"6","key":"886_CR32","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1093\/ije\/dyx034","volume":"46","author":"OO Yavorska","year":"2017","unstructured":"Yavorska OO, Burgess S (2017) MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol 46(6):1734\u20131739","journal-title":"Int J Epidemiol"},{"key":"886_CR33","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","author":"G Hemani","year":"2018","unstructured":"Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, Laurin C, Burgess S, Bowden J, Langdon R, Tan VY, Yarmolinsky J, Shihab HA, Timpson NJ, Evans DM, Relton C, Martin RM, Davey Smith G, Gaunt TR, Haycock PC (2018) The MR-Base platform supports systematic causal inference across the human phenome. Elife. https:\/\/doi.org\/10.7554\/eLife.34408","journal-title":"Elife"},{"issue":"5","key":"886_CR34","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1093\/gerona\/61.5.488","volume":"61","author":"LA Milliken","year":"2006","unstructured":"Milliken LA, Wilhelmy J, Martin CJ, Finkenthal N, Cussler E, Metcalfe L, Guido TA, Going SB, Lohman TG (2006) Depressive symptoms and changes in body weight exert independent and site-specific effects on bone in postmenopausal women exercising for 1 year. J Gerontol Series A Biol Sci Med Sci 61(5):488\u2013494","journal-title":"J Gerontol Series A Biol Sci Med Sci"},{"issue":"12","key":"886_CR35","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1001\/archinte.167.12.1240","volume":"167","author":"SJ Diem","year":"2007","unstructured":"Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, Ensrud KE (2007) Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med 167(12):1240\u20131245","journal-title":"Arch Intern Med"},{"issue":"36","key":"886_CR36","doi-asserted-by":"publisher","first-page":"e4655","DOI":"10.1097\/MD.0000000000004655","volume":"95","author":"BH Cheng","year":"2016","unstructured":"Cheng BH, Chen PC, Yang YH, Lee CP, Huang KE, Chen VC (2016) Effects of depression and antidepressant medications on hip fracture: a population-based cohort study in Taiwan. Medicine 95(36):e4655","journal-title":"Medicine"},{"key":"886_CR37","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.jad.2015.11.048","volume":"192","author":"LJ Williams","year":"2016","unstructured":"Williams LJ, Pasco JA, Jackson H, Kiropoulos L, Stuart AL, Jacka FN, Berk M (2016) Depression as a risk factor for fracture in women: a 10 year longitudinal study. J Affect Disord 192:34\u201340","journal-title":"J Affect Disord"},{"key":"886_CR38","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.bone.2016.05.003","volume":"89","author":"PH Rauma","year":"2016","unstructured":"Rauma PH, Honkanen RJ, Williams LJ, Tuppurainen MT, Kr\u00f6ger HP, Koivumaa-Honkanen H (2016) Effects of antidepressants on postmenopausal bone loss\u2014a 5-year longitudinal study from the OSTPRE cohort. Bone 89:25\u201331","journal-title":"Bone"},{"issue":"6","key":"886_CR39","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1007\/s00198-018-4420-1","volume":"29","author":"Q Wu","year":"2018","unstructured":"Wu Q, Liu B, Tonmoy S (2018) Depression and risk of fracture and bone loss: an updated meta-analysis of prospective studies. Osteoporos Int 29(6):1303\u20131312","journal-title":"Osteoporos Int"},{"issue":"4","key":"886_CR40","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/s40520-017-0789-5","volume":"30","author":"Y Liu","year":"2018","unstructured":"Liu Y, Wang Z, Xiao W (2018) Risk factors for mortality in elderly patients with hip fractures: a meta-analysis of 18 studies. Aging Clin Exp Res 30(4):323\u2013330","journal-title":"Aging Clin Exp Res"},{"issue":"7","key":"886_CR41","first-page":"2266","volume":"83","author":"S Khosla","year":"1998","unstructured":"Khosla S, Melton LJ 3rd, Atkinson EJ, O\u2019Fallon WM, Klee GG, Riggs BL (1998) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 83(7):2266\u20132274","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"886_CR42","first-page":"61","volume":"44","author":"I Gkiatas","year":"2015","unstructured":"Gkiatas I, Lykissas M, Kostas-Agnantis I, Korompilias A, Batistatou A, Beris A (2015) Factors affecting bone growth. Am J Orthop 44(2):61\u201367","journal-title":"Am J Orthop"},{"issue":"6","key":"886_CR43","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.jdiacomp.2013.07.007","volume":"27","author":"EJ Boyko","year":"2013","unstructured":"Boyko EJ (2013) Observational research\u2013opportunities and limitations. J Diabetes Complicat 27(6):642\u2013648","journal-title":"J Diabetes Complicat"},{"issue":"1","key":"886_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","volume":"32","author":"GD Smith","year":"2003","unstructured":"Smith GD, Ebrahim S (2003) \u2018Mendelian randomization\u2019: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 32(1):1\u201322","journal-title":"Int J Epidemiol"},{"issue":"7","key":"886_CR45","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1589\/jpts.27.2261","volume":"27","author":"AH Alghadir","year":"2015","unstructured":"Alghadir AH, Gabr SA, Al-Eisa E (2015) Physical activity and lifestyle effects on bone mineral density among young adults: sociodemographic and biochemical analysis. J Phys Ther Sci 27(7):2261\u20132270","journal-title":"J Phys Ther Sci"},{"issue":"1","key":"886_CR46","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1038\/s41467-018-03819-3","volume":"9","author":"DM Howard","year":"2018","unstructured":"Howard DM, Adams MJ, Shirali M, Clarke TK, Marioni RE, Davies G, Coleman JRI, Alloza C, Shen X, Barbu MC, Wigmore EM, Gibson J, Hagenaars SP, Lewis CM, Ward J, Smith DJ, Sullivan PF, Haley CS, Breen G, Deary IJ, McIntosh AM (2018) Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways. Nat Commun 9(1):1470","journal-title":"Nat Commun"}],"container-title":["Calcified Tissue International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00223-021-00886-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00223-021-00886-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00223-021-00886-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T14:04:13Z","timestamp":1634825053000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00223-021-00886-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["886"],"URL":"https:\/\/doi.org\/10.1007\/s00223-021-00886-5","relation":{},"ISSN":["0171-967X","1432-0827"],"issn-type":[{"value":"0171-967X","type":"print"},{"value":"1432-0827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]},"assertion":[{"value":"10 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Bin He, Qiong Lyu, Lifeng Yin, Muzi Zhang, Zhengxue Quan, Yunsheng Ou declared that they had no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The ethical approval for each study included in the investigation can be found in the original publications (including informed consent from each participant).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"All participants of the original studies included in the GWASs have provided the informed consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}]}}