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Osteoporosis International

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01-06-2021 | Diabetes | Original Article

Association between type 1 diabetes mellitus and reduced bone mineral density in children: a meta-analysis

Authors: Q. Zhu, J. Xu, M. Zhou, X. Lian, J. Xu, J. Shi

Published in: Osteoporosis International | Issue 6/2021

Abstract

Summary

In this meta-analysis, we analyzed 9 cross-sectional studies for an association between type 1 diabetes mellitus (T1DM) and bone mineral density (BMD) in children. We found that BMD Z-scores were significantly reduced in children with T1DM.

Introduction

Recent cross-sectional studies have examined how T1DM influences bone health in children and adolescents, but the relationship between T1DM and BMD remains unclear due to conflicting reports.

Methods

In this meta-analysis, we systematically searched PubMed, Cochrane library, and Web of Science databases (for publications through March 12, 2020), and calculated weight mean difference (WMD) along with 95% confidence intervals (CI) using a random-effects model. Heterogeneity was evaluated using the I² method. The Newcastle-Ottawa Scale was used to assess the quality of the included studies.

Results

Data were analyzed from 9 eligible studies, including a total of 1522 children and adolescents. These data were tested for an association between T1DM and BMD. This analysis found a significant decrease in BMD Z-score in the whole body (pooled WMD, − 0.47, 95% CI, − 0.92 to − 0.02, I² = 80.2%) and lumbar spine (pooled WMD, − 0.41, 95% CI, − 0.69 to − 0.12, I² = 80.3%) in children and adolescents with T1DM, which was consistent in published studies from Asia and South America, but inconsistent in the North America and Europe. Importantly, the differences in BMD Z-scores were independent of age, level of glucose control (HbA1c), and prepubertal stage. Sensitivity analyses did not modify these findings. Funnel plot and the Egger test did not reveal significant publication bias.

Conclusion

This meta-analysis suggests that T1DM may play a role in decreasing BMD Z-scores in the whole body and lumbar spine in children.

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Patterson C, Guariguata L, Dahlquist G, Soltész G, Ogle G, Silink M (2014) Diabetes in the young a global view and worldwide estimates of numbers of children with type 1 diabetes. Diabetes Res Clin Pract 103(2):161–175. https://doi.org/10.1016/j.diabres.2013.11.005CrossRefPubMed

Craig ME, Jefferies C, Dabelea D, Balde N, Donaghue KC (2014) Definition, epidemiology, and classification of diabetes in children and adolescents (ISPAD Clinical Practice Consensus Guidelines 2014 Compendium). Pediatr Diabetes 15(Suppl 20):4–17. https://doi.org/10.1111/pedi.12186CrossRefPubMed

Wołoszyn-Durkiewicz A, Myśliwiec M (2019) The prognostic value of inflammatory and vascular endothelial dysfunction biomarkers in microvascular and macrovascular complications in type 1 diabetes. Pediatr Endocrinol Diabetes Metab 25(1):28–35. https://doi.org/10.5114/pedm.2019.84710CrossRefPubMed

Saki F, Sheikhi A, Omrani GHR, Karimi H, Dabbaghmanesh MH, Mousavinasab SN (2017) Evaluation of bone mineral density in children with type I diabetes mellitus and relationship to serum levels of osteopontin. Drug Res (Stuttg) 67(9):527–533. https://doi.org/10.1055/s-0043-109001CrossRef

Léger J, Marinovic D, Alberti C, Dorgeret S, Chevenne D, Marchal CL, Tubiana RN, Sebag G, Czernichow P (2006) Lower bone mineral content in children with type 1 diabetes mellitus is linked to female sex, low insulin-like growth factor type I levels, and high insulin requirement. J Clin Endocrinol Metab 91(10):3947–3953. https://doi.org/10.1210/jc.2006-0711CrossRefPubMed

Karagüzel G, Akçurin S, Ozdem S, Boz A, Bircan I (2006) Bone mineral density and alterations of bone metabolism in children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 19(6):805–814. https://doi.org/10.1515/jpem.2006.19.6.805CrossRefPubMed

Raisingani M, Preneet B, Kohn B, Yakar S (2017) Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis. Growth Horm IGF Res 34:13–21. https://doi.org/10.1016/j.ghir.2017.04.003CrossRefPubMedPubMedCentral

Cotts KG, Cifu AS (2018) Treatment of osteoporosis. JAMA 319:1040–1041. https://doi.org/10.1001/jama.2017.21995CrossRefPubMed

Black DM, Rosen CJ (2016) Postmenopausal osteoporosis. N Engl J Med 374:2096–2097. https://doi.org/10.1056/NEJMc1602599CrossRefPubMed

10.

Braithwaite RS, Col NF, Wong JB (2003) Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc 51(3):364–370. https://doi.org/10.1046/j.1532-5415.2003.51110.xCrossRefPubMed

11.

Panagiotis A, Stavroula AP, Nifon NG, Aikaterini MA, Konstantinos C, Dimitrios S, Andromachi V, Michael P, Dimitrios GG (2018) Efficacy of anti-osteoporotic medications in patients with type 1 and 2 diabetes mellitus: a systematic review. Endocrine 60(3):373–383. https://doi.org/10.1007/s12020-018-1548-xCrossRef

12.

Shah VN, Harrall KK, Shah CS, Gallo TL, Joshee P, Snell-Bergeon JK, Kohrt WM (2017) Bone mineral density at femoral neck and lumbar spine in adults with type 1 diabetes: a meta-analysis and review of the literature. Osteoporos Int 28(9):2601–2610. https://doi.org/10.1007/s00198-017-4097-xCrossRefPubMed

13.

Brandao FR, Vicente EJ, Daltro CH, Sacramento M, Moreira A, Adan L (2007) Bone metabolism is linked to disease duration and metabolic control in type 1 diabetes mellitus. Diabetes Res Clin Pract 78(3):334–339. https://doi.org/10.1016/j.diabres.2007.04.009CrossRefPubMed

14.

de Souza KS, Ururahy MA, da Costa Oliveira YM, Loureiro MB, da Silva HP, Bortolin RH, Melo Dos Santos F, Luchessi AD, Neto JJ, Arrais RF, Hirata RD, das Graças Almeida M, Hirata MH, de Rezende AA (2016) Low bone mineral density in patients with type 1 diabetes: association with reduced expression of IGF1, IGF1R and TGFB1 in peripheral blood mononuclear cells. Diabetes Metab Res Rev 32(6):589–595. https://doi.org/10.1002/dmrr.2772CrossRefPubMed

15.

Dongare BS, Lohiya N, Maheshwari A, Ekbote V, Chiplonkar S, Padidela R, Mughal Z, Khadilkar V, Khadilkar A (2020) Muscle and bone parameters in underprivileged Indian children and adolescents with T1DM. Bone 130:115074. https://doi.org/10.1016/j.bone.2019.115074CrossRef

16.

Gunczler P, Lanes R, Paoli M, Martinis R, Villaroel O, Weisinger JR (2001) Decreased bone mineral density and bone formation markers - shortly after diagnosis of clinical type 1 diabetes mellitus. J Pediatr Endocrinol Metab 14(5):525–528. https://doi.org/10.1515/jpem.2001.14.5.525CrossRefPubMed

17.

Loureiro MB, Ururahy Marcela AG, Souza Karla SC, Oliveira Yonara MC, Silva Heglayne PV, Bortolin RH, Bezerra JF, Hirata Rosario DC, Maciel-Neto JJ, Arrais RF, Almeida Maria dG, Hirata MH, Rezende Adriana A (2018) Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus. Braz J Pharm Sci 53(4):e00060. https://doi.org/10.1590/s2175-97902017000400060CrossRef

18.

Maggio AB, Ferrari S, Kraenzlin M, Marchand LM, Schwitzgebel V, Beghetti M, Rizzoli R, Farpour-Lambert NJ (2010) Decreased bone turnover in children and adolescents with well controlled type 1 diabetes. J Pediatr Endocrinol Metab 23(7):697–707. https://doi.org/10.1515/jpem.2010.23.7.697CrossRefPubMed

19.

Roh JG, Yoon JS, Park KJ, Lim JS, Lee HS, Hwang JS (2018) Evaluation of bone mineral status in prepuberal children with newly diagnosed type 1 diabetes. Ann Pediatr Endocrinol Metab 23(3):136–140. https://doi.org/10.6065/apem.2018.23.3.136CrossRefPubMedPubMedCentral

20.

Simmons KM, McFann K, Taki I, Liu E, Klingensmith GJ, Rewers MJ, Frohnert BI (2016) Reduced bone mineral density is associated with celiac disease autoimmunity in children with type 1 diabetes. J Pediatr 169:44–48.e1. https://doi.org/10.1016/j.jpeds.2015.10.024CrossRefPubMed

21.

Tsentidis C, Gourgiotis D, Kossiva L, Doulgeraki A, Marmarinos A, Galli-Tsinopoulou A, Karavanaki K (2016) Higher levels of s-RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis. Osteoporos Int 27(4):1631–1643. https://doi.org/10.1007/s00198-015-3422-5CrossRefPubMed

22.

Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. https://doi.org/10.1136/bmj.b2535

23.

Bashashati M, Rezaei N, Shafieyoun A, McKernan DP, Chang L, Öhman L, Quigley EM, Schmulson M, Sharkey KA, Simrén M (2014) Cytokine imbalance in irritable bowel syndrome: a systematic review and meta-analysis. Neurogastroenterol Motil 26(7):1036–1048. https://doi.org/10.1111/nmo.12358CrossRefPubMed

24.

Islam MA, Alam F, Wong KK (2017) Comorbid association of antiphospholipid antibodies and migraine: a systematic review and meta-analysis. Autoimmun Rev 16(5):512–522. https://doi.org/10.1016/j.autrev.2017.03.005CrossRefPubMed

25.

Islam MA, Alam F, Cavestro C, Calcii C, Sasongko TH, Levy RA, Gan SH (2018) Antiphospholipid antibodies in epilepsy: a systematic review and meta-analysis. Autoimmun Rev 17(8):755–767. https://doi.org/10.1016/j.autrev.2018.01.025CrossRefPubMed

26.

Higgins Julian PT, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0. [updated March 2011]. The Cochrane Collaboration. www.cochrane-handbook.org. Accessed 30 Sept 2018

27.

Higgins Julian PT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. https://doi.org/10.1002/sim.1186CrossRefPubMed

28.

Pan H, Wu N, Yang T, Wei H (2014) Association between bone mineral density and type 1 diabetes mellitus: a meta-analysis of cross-sectional studies. Diabetes/Metab Res Rev 30(7):531–542. https://doi.org/10.1002/dmrr.2508CrossRef

29.

McKay HA, Petit MA, Khan KM, Schutz RW (2000) Lifestyle determinants of bone mineral: a comparison between prepubertal Asian- and Caucasian-Canadian boys and girls. Calcif Tissue Int 66(5):320–324. https://doi.org/10.1007/s002230010067CrossRefPubMed

30.

Boot AM, de Ridder MA, Pols HA, Krenning EP, de Muinck Keizer-Schrama SM (1997) Bone mineral density in children and adolescents: relation to puberty, calcium intake, and physical activity. J Clin Endocrinol Metab 82(1):57–62. https://doi.org/10.1210/jcem.82.1.3665CrossRefPubMed

31.

Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL (2017) IOF Bone and Diabetes Working Group. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol 13(4):208–219. https://doi.org/10.1038/nrendo.2016.153CrossRefPubMed

32.

Hough FS, Pierroz DD, Cooper C, Ferrari SL (2016) MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus. Eur J Endocrinol 174(4):R127–R138. https://doi.org/10.1530/EJE-15-0820CrossRefPubMed

33.

Linda G, Xiaofei H, Paul F, Scott B, Mirek K, Janet R, Mark SN (2000) Inhibition of osteoblast differentiation by tumor necrosis factor-alpha. Endocrinology 141(11):3956–3964. https://doi.org/10.1210/endo.141.11.7739CrossRef

34.

Glantschnig H, Fisher JE, Wesolowski G, Rodan GA, Reszka AA (2003) M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell Death Differ 10(10):1165–1177. https://doi.org/10.1038/sj.cdd.4401285CrossRefPubMed

35.

Manolagas SC (2010) From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 31(3):266–300. https://doi.org/10.1210/er.2009-0024CrossRefPubMedPubMedCentral

36.

McCabe LR (2007) Understanding the pathology and mechanisms of type I diabetic bone loss. J Cell Biochem 102(6):1343–1357. https://doi.org/10.1002/jcb.21573CrossRefPubMed

37.

Botolin S, McCabe LR (2006) Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. J Cell Biochem 99(2):411–424. https://doi.org/10.1002/jcb.20842CrossRefPubMed

38.

Sanguineti R, Puddu A, Mach F, Montecucco F, Viviani GL (2014) Advanced glycation end products play adverse proinflammatory activities in osteoporosis. Mediators Inflamm 2014(9):975872–975879. https://doi.org/10.1155/2014/975872CrossRefPubMedPubMedCentral

39.

Neumann T, Lodes S, Kästner B, Franke S, Kiehntopf M, Lehmann T, Müller UA, Wolf G, Sämann A (2014) High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control. Osteoporos Int 25(5):1527–1533. https://doi.org/10.1007/s00198-014-2631-7CrossRefPubMed

40.

Hofbauer LC, Brueck CC, Singh SK, Dobnig H (2007) Osteoporosis in patients with diabetes mellitus. J Bone Mineral Res 22(9):1317–1328. https://doi.org/10.1359/jbmr.070510CrossRef

41.

Maggio AB, Rizzoli RR, Marchand LM, Ferrari S, Beghetti M, Farpour-Lambert NJ (2012) Physical activity increases bone mineral density in children with type 1 diabetes. Med Sci Sports Exerc 44(7):1206–1211. https://doi.org/10.1249/MSS.0b013e3182496a25CrossRefPubMed

42.

Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136. https://doi.org/10.1007/s11657-013-0136-1CrossRefPubMedPubMedCentral

Title: Association between type 1 diabetes mellitus and reduced bone mineral density in children: a meta-analysis
Authors: Q. Zhu
J. Xu
M. Zhou
X. Lian
J. Xu
J. Shi
Publication date: 01-06-2021
Publisher: Springer London
Keywords: Diabetes
Type 1 Diabetes
Published in: Osteoporosis International / Issue 6/2021
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-020-05715-3

At a glance: The STEP trials

Springer Medicine

Association between type 1 diabetes mellitus and reduced bone mineral density in children: a meta-analysis

Abstract

Summary

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

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