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The association between type 2 diabetes mellitus, hip fracture, and post-hip fracture mortality: a multi-state cohort analysis

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Abstract

Summary

Type 2 diabetes mellitus (T2DM) is associated with an excess risk of fractures and overall mortality. This study compared hip fracture and post-hip fracture mortality in T2DM and non-diabetic subjects. The salient findings are that subjects in T2DM are at higher risk of dying after suffering a hip fracture.

Introduction

Previous research suggests that individuals with T2DM are at an excess risk of both fractures and overall mortality, but their combined effect is unknown. Using multi-state cohort analyses, we estimate the association between T2DM and the transition to hip fracture, post-hip fracture mortality, and hip fracture–free all-cause death.

Methods

Population-based cohort from Catalonia, Spain, including all individuals aged 65 to 80 years with a recorded diagnosis of T2DM on 1 January 2006; and non-T2DM matched (up to 2:1) by year of birth, gender, and primary care practice.

Results

A total of 44,802 T2DM and 81,233 matched controls (53% women, mean age 72 years old) were followed for a median of 8 years: 23,818 died without fracturing and 3317 broke a hip, of whom 838 subsequently died. Adjusted HRs for hip fracture–free mortality were 1.32 (95% CI 1.28 to 1.37) for men and 1.72 (95% CI 1.65 to 1.79) for women. HRs for hip fracture were 1.24 (95% CI 1.08 to 1.43) and 1.48 (95% CI 1.36 to 1.60), whilst HRs for post-hip fracture mortality were 1.28 (95% CI 1.02 to 1.60) and 1.57 (95% CI 1.31 to 1.88) in men and women, respectively.

Conclusion

T2DM individuals are at increased risk of hip fracture, post-hip fracture mortality, and hip fracture–free death. After adjustment, T2DM men were at a 28% higher risk of dying after suffering a hip fracture and women had 57% excess risk of post-hip fracture mortality.

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References

  1. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B (2018) IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138:271–281. https://doi.org/10.1016/j.diabres.2018.02.023

    Article  CAS  PubMed  Google Scholar 

  2. Lutgers HL, Gerrits EG, Sluiter WJ, Ubink-Veltmaat LJ, Landman GWD, Links TP, Gans ROB, Smit AJ, Bilo HJG Life expectancy in a large cohort of type 2 diabetes patients treated in primary care (ZODIAC-10). Sorensen TIA, ed. PLoS One 2009;4(8):e6817. doi:https://doi.org/10.1371/journal.pone.0006817

  3. Szuszkiewicz-Garcia MM, Davidson JA (2014) Cardiovascular disease in diabetes mellitus. Endocrinol Metab Clin N Am 43(1):25–40. https://doi.org/10.1016/j.ecl.2013.09.001

    Article  Google Scholar 

  4. Narres M, Claessen H, Droste S, Kvitkina T, Koch M, Kuss O, Icks A (2016) The incidence of end-stage renal disease in the diabetic (compared to the non-diabetic) population: a systematic review. Jandeleit-Dahm K, ed. PLoS One 11(1):e0147329. https://doi.org/10.1371/journal.pone.0147329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Salvotelli L, Stoico V, Perrone F, Cacciatori V, Negri C, Brangani C, Pichiri I, Targher G, Bonora E, Zoppini G (2015) Prevalence of neuropathy in type 2 diabetic patients and its association with other diabetes complications: the Verona Diabetic Foot Screening Program. J Diabetes Complicat 29(8):1066–1070. https://doi.org/10.1016/j.jdiacomp.2015.06.014

    Article  Google Scholar 

  6. Olafsdottir E, Andersson DKG, Dedorsson I, Stefánsson E (2014) The prevalence of retinopathy in subjects with and without type 2 diabetes mellitus. Acta Ophthalmol 92(2):133–137. https://doi.org/10.1111/aos.12095

    Article  PubMed  Google Scholar 

  7. Schaper NC, Van Netten JJ, Apelqvist J, Lipsky BA, Bakker K (2016) International Working Group on the Diabetic Foot. Prevention and management of foot problems in diabetes: a summary guidance for daily practice 2015, based on the IWGDF guidance documents. Diabetes Metab Res Rev 32:7–15. https://doi.org/10.1002/dmrr.2695

    Article  PubMed  Google Scholar 

  8. Martinez-Laguna D, Tebe C, Javaid MK, Nogues X, Arden NK, Cooper C, Diez-Perez A, Prieto-Alhambra D (2015) Incident type 2 diabetes and hip fracture risk: a population-based matched cohort study. Osteoporos Int 26(2):827–833. https://doi.org/10.1007/s00198-014-2986-9

    Article  CAS  PubMed  Google Scholar 

  9. Dede AD, Tournis S, Dontas I, Trovas G (2014) Type 2 diabetes mellitus and fracture risk. Metabolism. 63(12):1480–1490. https://doi.org/10.1016/j.metabol.2014.09.002

    Article  CAS  PubMed  Google Scholar 

  10. Friedman SM, Mendelson DA (2014) Epidemiology of fragility fractures. Clin Geriatr Med 30(2):175–181. https://doi.org/10.1016/j.cger.2014.01.001

    Article  PubMed  Google Scholar 

  11. Svedbom A, Hernlund E, Ivergård M et al (2013) Osteoporosis in the European Union: a compendium of country-specific reports. Arch Osteoporos 8(1–2):137. https://doi.org/10.1007/s11657-013-0137-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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. Arch Osteoporos 8(1–2):136. https://doi.org/10.1007/s11657-013-0136-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Abimanyi-Ochom J, Watts JJ, Borgström F, Nicholson GC, Shore-Lorenti C, Stuart AL, Zhang Y, Iuliano S, Seeman E, Prince R, March L, Cross M, Winzenberg T, Laslett LL, Duque G, Ebeling PR, Sanders KM (2015) Changes in quality of life associated with fragility fractures: Australian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (AusICUROS). Osteoporos Int 26(6):1781–1790. https://doi.org/10.1007/s00198-015-3088-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. LeBlanc KE, Muncie HL, LeBlanc LL (2014) Hip fracture: diagnosis, treatment, and secondary prevention. Am Fam Physician 89(12):945–951 http://www.ncbi.nlm.nih.gov/pubmed/25162161 .Accessed April 22, 2018

  15. Burns A, Younger J, Morris J, Baldwin R, Tarrier N, Pendleton N, Cohen P, Horan M, Banerjee S (2014) Outcomes following hip fracture surgery: a 2-year prospective study. Am J Geriatr Psychiatry 22(8):838–844. https://doi.org/10.1016/j.jagp.2013.01.047

    Article  PubMed  Google Scholar 

  16. Simunovic N, Devereaux PJ, Sprague S, Guyatt GH, Schemitsch E, DeBeer J, Bhandari M (2010) Effect of early surgery after hip fracture on mortality and complications: systematic review and meta-analysis. Can Med Assoc J 182(15):1609–1616. https://doi.org/10.1503/cmaj.092220

    Article  Google Scholar 

  17. Magaziner J, Hawkes W, Hebel JR, Zimmerman SI, Fox KM, Dolan M, Felsenthal G, Kenzora J (2000) Recovery from hip fracture in eight areas of function. J Gerontol A Biol Sci Med Sci 55(9):M498–M507 http://www.ncbi.nlm.nih.gov/pubmed/10995047. Accessed April 22, 2018

    Article  CAS  PubMed  Google Scholar 

  18. Roche JJW, Wenn RT, Sahota O, Moran CG (2005) Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study. BMJ. 331(7529):1374. https://doi.org/10.1136/bmj.38643.663843.55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Putter H, Fiocco M, Gekus RB (2007) Tutorial in biostatistics: competing risk and multi-state models. Stat Med 26(11):2389–2430. https://doi.org/10.1002/sim.2712

    Article  CAS  PubMed  Google Scholar 

  20. Schmoor C, Schumacher M, Finke J, Beyersmann J (2013) Competing risks and multistate models. Clin Cancer Res 19(1):12–21. https://doi.org/10.1158/1078-0432.CCR-12-1619

    Article  PubMed  Google Scholar 

  21. Bolíbar B, Fina Avilés F, Morros R, del Mar Garcia-Gil M, Hermosilla E, Ramos R, Rosell M, Rodríguez J, Medina M, Calero S, Prieto-Alhambra D (2012) SIDIAP database: electronic clinical records in primary care as a source of information for epidemiologic research. Med Clin (Barc) 138(14):617–621. https://doi.org/10.1016/j.medcli.2012.01.020

    Article  Google Scholar 

  22. Martinez-Laguna D, Soria-Castro A, Carbonell-Abella C, Orozco-López P, Estrada-Laza P, Nogues X, Díez-Perez A, Prieto-Alhambra D (2017) Validation of fragility fractures in primary care electronic medical records: a population-based study. Reumatol Clin. https://doi.org/10.1016/j.reuma.2017.10.013

  23. Pagès-Castell A, Carbonell-Abella C, Avilés FF et al (2012) Burden of osteoporotic fractures in primary health care in Catalonia (Spain): a population-based study. BMC Musculoskelet Disord 13(1):79. https://doi.org/10.1186/1471-2474-13-79

    Article  Google Scholar 

  24. Tebé C, Martinez-Laguna D, Moreno V, Cooper C, Diez-Perez A, Collins GS, Prieto-Alhambra D (2018) Differential mortality and the excess rates of hip fracture associated with type 2 diabetes: accounting for competing risks in fracture prediction matters. J Bone Miner Res 33(8):1417–1421. https://doi.org/10.1002/jbmr.3435

    Article  CAS  PubMed  Google Scholar 

  25. Beyersmann J, Allignol A, Schumacher M (2012) Competing risks and multistate models with R. https://doi.org/10.1007/978-1-4614-2035-4

    Book  Google Scholar 

  26. Nwaneri C, Cooper H, Bowen-Jones D (2013) Mortality in type 2 diabetes mellitus: magnitude of the evidence from a systematic review and meta-analysis. Br J Diabetes Vasc Dis 13(4):192–207. https://doi.org/10.1177/1474651413495703

    Article  Google Scholar 

  27. Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166(5):495–505. https://doi.org/10.1093/aje/kwm106

    Article  PubMed  Google Scholar 

  28. Jia P, Bao L, Chen H, Yuan J, Liu W, Feng F, Li J, Tang H (2017) Risk of low-energy fracture in type 2 diabetes patients: a meta-analysis of observational studies. Osteoporos Int 28(11):3113–3121. https://doi.org/10.1007/s00198-017-4183-0

    Article  CAS  PubMed  Google Scholar 

  29. Moayeri A, Mohamadpour M, Mousavi SF, Shirzadpour E, Mohamadpour S, Amraei M (2017) Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis. Ther Clin Risk Manag 13:455–468. https://doi.org/10.2147/TCRM.S131945

    Article  PubMed  PubMed Central  Google Scholar 

  30. Dytfeld J, Michalak M (2017) Type 2 diabetes and risk of low-energy fractures in postmenopausal women: meta-analysis of observational studies. Aging Clin Exp Res 29(2):301–309. https://doi.org/10.1007/s40520-016-0562-1

    Article  PubMed  Google Scholar 

  31. Tebé C, Martinez-Laguna D, Moreno V, Cooper C, Diez-Perez A, Collins GS, Prieto-Alhambra D (2018) Differential mortality and the excess rates of hip fracture associated with type 2 diabetes: accounting for competing risks in fracture prediction matters. J Bone Miner Res 33:1417–1421. https://doi.org/10.1002/jbmr.3435

    Article  CAS  PubMed  Google Scholar 

  32. Khan MA, Hossain FS, Ahmed I, Muthukumar N, Mohsen A (2013) Predictors of early mortality after hip fracture surgery. Int Orthop 37(11):2119–2124. https://doi.org/10.1007/s00264-013-2068-1

    Article  PubMed  PubMed Central  Google Scholar 

  33. Smith T, Pelpola K, Ball M, Ong A, Myint PK (2014) Pre-operative indicators for mortality following hip fracture surgery: a systematic review and meta-analysis. Age Ageing 43(4):464–471. https://doi.org/10.1093/ageing/afu065

    Article  PubMed  Google Scholar 

  34. Hu F, Jiang C, Shen J, Tang P, Wang Y (2012) Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis. Injury. 43(6):676–685. https://doi.org/10.1016/j.injury.2011.05.017

    Article  PubMed  Google Scholar 

  35. Haentjens P, Magaziner J, Colón-Emeric CS et al (2010) Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med 152(6):380. https://doi.org/10.7326/0003-4819-152-6-201003160-00008

    Article  PubMed  PubMed Central  Google Scholar 

  36. Muraki S, Yamamoto S, Ishibashi H, Nakamura K (2006) Factors associated with mortality following hip fracture in Japan. J Bone Miner Metab 24(2):100–104. https://doi.org/10.1007/s00774-005-0654-z

    Article  PubMed  Google Scholar 

  37. Paksima N, Koval KJ, Aharanoff G, Walsh M, Kubiak EN, Zuckerman JD, Egol KA (2008) Predictors of mortality after hip fracture: a 10-year prospective study. Bull NYU Hosp Jt Dis 66(2):111–117 http://www.ncbi.nlm.nih.gov/pubmed/18537780. Accessed April 24, 2018

    PubMed  Google Scholar 

  38. Palermo A, D’Onofrio L, Eastell R, Schwartz AV, Pozzilli P, Napoli N (2015) Oral anti-diabetic drugs and fracture risk, cut to the bone: safe or dangerous? A narrative review. Osteoporos Int 26(8):2073–2089. https://doi.org/10.1007/s00198-015-3123-0

    Article  CAS  PubMed  Google Scholar 

  39. Zhu Z-N, Jiang Y-F, Ding T (2014) Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone. 68:115–123. https://doi.org/10.1016/j.bone.2014.08.010

    Article  CAS  PubMed  Google Scholar 

  40. Ferrari SL, Abrahamsen B, Napoli N et al (2018) Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int 29(12):2585–2596. https://doi.org/10.1007/s00198-018-4650-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kleinbaum DG, Klein M (2012) Survival analysis : a self-learning text. Springer

  42. Huang T-S, Lin C-L, Lu M-J, Yeh CT, Liang KH, Sun CC, Shyu YC, Chien RN (2017) Diabetes, hepatocellular carcinoma, and mortality in hepatitis C-infected patients: a population-based cohort study. J Gastroenterol Hepatol 32(7):1355–1362. https://doi.org/10.1111/jgh.13670

    Article  CAS  PubMed  Google Scholar 

  43. Ley SH, Hamdy O, Mohan V, Hu FB (2014) Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet. 383:1999–2007. https://doi.org/10.1016/S0140-6736(14)60613-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW (2008) 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359(15):1577–1589. https://doi.org/10.1056/NEJMoa0806470

    Article  CAS  PubMed  Google Scholar 

  45. Martínez-Laguna D, Reyes C, Carbonell-Abella C et al (2017) Use of drugs for osteoporosis treatment in patients with type 2 diabetes mellitus: population-based cohort study. Rev Osteoporos y Metab Miner 9(4):107–112. https://doi.org/10.4321/S1889-836X2017000400002LK

    Article  Google Scholar 

  46. Vestergaard P, Rejnmark L, Mosekilde L (2011) Are antiresorptive drugs effective against fractures in patients with diabetes? Calcif Tissue Int 88(3):209–214. https://doi.org/10.1007/s00223-010-9450-4

    Article  CAS  PubMed  Google Scholar 

  47. Tuominen JT, Impivaara O, Puukka P, Rönnemaa T (1999) Bone mineral density in patients with type 1 and type 2 diabetes. Diabetes Care 22(7):1196–1200

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Cristian Tebé and Daniel Prieto-Alhambra designed the study, performed data management and statistical analysis, and drafted the paper. Daniel Martínez-Laguna, Cristina Carbonell-Abella, Carlen Reyes, Victor Moreno, Adolf Diez-Perez, and Gary Collins supervised epidemiological/analytical aspects, participated in the discussion and interpretation of results, and reviewed and critically edited the paper. All authors read the final version and approved submission.

The authors would like to acknowledge the significant contributions of Paloma O’Dogherty (Research Facilitator), Elaine Lilly, Ph.D. (English editor) and the SIDIAP data management team. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health of the United Kingdom.

Funding

This work was supported by the NIHR Biomedical Research Centre, Oxford. DPA is funded by a National Institute for Health Research Clinician Scientist award (CS-2013-13-012). This article presents independent research funded by the National Institute for Health Research (NIHR). Also, CIBER (Instituto Carlos III) and FEDER funds contributed to the support of the investigation.

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Authors and Affiliations

  1. Biostatistics Unit at Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Spain

    C. Tebé & V. Moreno

  2. Universitat de Barcelona, Barcelona, Spain

    C. Tebé & V. Moreno

  3. Universitat Rovira i Virgili, Reus, Spain

    C. Tebé

  4. Atenció Primària Barcelona Ciutat, Institut Català de la Salut, Barcelona, Spain

    D. Martínez-Laguna & C. Carbonell-Abella

  5. Grupo de Investigación GREMPAL, IDIAP Jordi Gol and CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain

    D. Martínez-Laguna, C. Carbonell-Abella, C. Reyes & D. Prieto-Alhambra

  6. Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, 08908, L’Hospitalet de Llobregat, Spain

    V. Moreno

  7. CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

    V. Moreno

  8. Musculoskeletal Research Unit, IMIM-Hospital del Mar and CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, 08003, Barcelona, Spain

    A. Diez-Perez

  9. Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS), University of Oxford, Windmill Road, Oxford, UK

    G.S. Collins & D. Prieto-Alhambra

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  1. C. Tebé
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  2. D. Martínez-Laguna
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  7. G.S. Collins
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  8. D. Prieto-Alhambra
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Correspondence to D. Prieto-Alhambra.

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Conflicts of interest

Cristian Tebé has received lecture fees and honoraria from Boehringer Ingelheim and Amgen outside of the submitted work. Daniel Prieto-Alhambra has received lecture fees and honoraria from Servier, Amgen, and UCB Biopharma SRL outside of the submitted work. Adolf Diez has received lecture fees and honoraria from Amgen, Amgen, Lilly, Gilead, UCB, Roche, Amgen, and EchoLight outside of the submitted work. Daniel Martinez-Laguna, Cristina Carbonell, Carlen Reyes, Victor Moreno, and Gary S Collins declare that they have no conflict of interest.

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Tebé, C., Martínez-Laguna, D., Carbonell-Abella, C. et al. The association between type 2 diabetes mellitus, hip fracture, and post-hip fracture mortality: a multi-state cohort analysis. Osteoporos Int 30, 2407–2415 (2019). https://doi.org/10.1007/s00198-019-05122-3

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