, Volume 57, Issue 10, pp 2057–2065 | Cite as

Fracture risk in diabetic elderly men: the MrOS study

  • Nicola NapoliEmail author
  • Elsa S. Strotmeyer
  • Kristine E. Ensrud
  • Deborah E. Sellmeyer
  • Douglas C. Bauer
  • Andrew R. Hoffman
  • Thuy-Tien L. Dam
  • Elizabeth Barrett-Connor
  • Lisa Palermo
  • Eric S. Orwoll
  • Steven R. Cummings
  • Dennis M. Black
  • Ann V. Schwartz



Diabetes mellitus is associated with increased fracture risk in women but few studies are available in men. To evaluate the relationship between diabetes and prospective non-vertebral fractures in elderly men, we used data from the Osteoporotic Fractures in Men (MrOS) study.


The MrOS enrolled 5,994 men (aged ≥65 years). Diabetes (ascertained by self-report, the use of medication for diabetes or an elevated fasting glucose level) was reported in 881 individuals, 80 of whom were using insulin. Hip and spine bone mineral density (BMD) was measured using dual x-ray absorptiometry (DXA). After recruitment, the men were followed for incident non-vertebral fractures using a triannual (3 yearly) questionnaire for an average of 9.1 (SD 2.7) years. The Cox proportional hazards model was used to assess the incident risk of fractures.


In models adjusted for age, race, clinic site and total hip BMD, the risk of non-vertebral fracture was higher in men with diabetes compared with normoglycaemic men (HR 1.30, 95% CI 1.09, 1.54) and was elevated in men using insulin (HR 2.46, 95% CI 1.69, 3.59). Men with impaired fasting glucose did not have a higher risk of fracture compared with normoglycaemic men (HR 1.04, 95% CI 0.89, 1.21). After multivariable adjustment, the risk of non-vertebral fracture remained higher only among men with diabetes who were using insulin (HR 1.74, 95% CI 1.13, 2.69).


Men with diabetes who are using insulin have an increased risk of non-vertebral fracture for a given age and BMD.


Bone Diabetes Fractures Impaired fasting glucose Insulin Osteoporosis 



Bone mineral density


Chronic Kidney Disease Epidemiology Collaboration


Dual energy x-ray absorptiometry


Impaired fasting glucose


Osteoporotic Fractures in Men


Physical Activity Scale for the Elderly





The authors wish to thank C. C. Dant of Medcom Consulting for his expert assistance preparing this manuscript. The authors represent the Osteoporotic Fractures in Men (MrOS) research group.


The Osteoporotic Fractures in Men (MrOS) study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR) and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01AG18197, U01-AG027810, and UL1 RR024140. Glucose measurements were supported by a grant from the American ADA (1-04-JF-46, Strotmeyer ES).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

NN was involved in the concept, in data interpretation and in writing the manuscript. KEE and ESS were involved in the concept and design of the study, the acquisition and interpretation of data and the critical review of the paper for important intellectual content. ARH, DES, TLD, EB-C, DCB, DMB, ESO and SRC took part in the acquisition and interpretation of the data and in revising the article for important intellectual content. LP was involved in data acquisition and analysis and in revising the article. AVS is the guarantor of the study and made substantial contributions to the conception and design of the study, to the analysis and interpretation of the data, and to revising the article critically for important intellectual content. All authors gave their approval of the final manuscript.


  1. 1.
    Schwartz AV, Sellmeyer DE, Ensrud KE et al (2001) Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 86:32–38PubMedCrossRefGoogle Scholar
  2. 2.
    Bonds DE, Larson JC, Schwartz AV et al (2006) Risk of fracture in women with type 2 diabetes: the Women's Health Initiative Observational Study. J Clin Endocrinol Metab 91:3404–3410PubMedCrossRefGoogle Scholar
  3. 3.
    Nicodemus KK, Folsom AR (2001) Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 24:1192–1197PubMedCrossRefGoogle Scholar
  4. 4.
    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 166:495–505PubMedCrossRefGoogle Scholar
  5. 5.
    Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444PubMedCrossRefGoogle Scholar
  6. 6.
    Isidro ML, Ruano B (2010) Bone disease in diabetes. Curr Diabetes Rev 6:144–155PubMedCrossRefGoogle Scholar
  7. 7.
    Ahmed LA, Joakimsen RM, Berntsen GK, Fonnebo V, Schirmer H (2006) Diabetes mellitus and the risk of non-vertebral fractures: the Tromso study. Osteoporos Int 17:495–500PubMedCrossRefGoogle Scholar
  8. 8.
    de Liefde I, van der Klift M, de Laet CE, van Daele PL, Hofman A, Pols HA (2005) Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 16:1713–1720PubMedCrossRefGoogle Scholar
  9. 9.
    Holmberg AH, Johnell O, Nilsson PM, Nilsson J, Berglund G, Akesson K (2006) Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women. Osteoporos Int 17:1065–1077PubMedCrossRefGoogle Scholar
  10. 10.
    Melton LJ 3rd, Leibson CL, Achenbach SJ, Therneau TM, Khosla S (2008) Fracture risk in type 2 diabetes: update of a population-based study. J Bone Miner Res 23:1334–1342PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Blank JB, Cawthon PM, Carrion-Petersen ML et al (2005) Overview of recruitment for the Osteoporotic Fractures in Men study (MrOS). Contemp Clin Trials 26:557–568PubMedCrossRefGoogle Scholar
  12. 12.
    Orwoll E, Blank JB, Barrett-Connor E et al (2005) Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study – a large observational study of the determinants of fracture in older men. Contemp Clin Trials 26:569–585PubMedCrossRefGoogle Scholar
  13. 13.
    American Diabetes Association (2012) Standards of medical care in diabetes – 2012. Diabetes Care 35(Suppl 1):S11–S63Google Scholar
  14. 14.
    Lewis CE, Ewing SK, Taylor BC et al (2007) Predictors of non-spine fracture in elderly men: the MrOS study. J Bone Miner Res 22:211–219PubMedCrossRefGoogle Scholar
  15. 15.
    Mackey DC, Lui LY, Cawthon PM et al (2007) High-trauma fractures and low bone mineral density in older women and men. JAMA 298:2381–2388PubMedCrossRefGoogle Scholar
  16. 16.
    Sanders KM, Pasco JA, Ugoni AM et al (1998) The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study. J Bone Miner Res 13:1337–1342PubMedCrossRefGoogle Scholar
  17. 17.
    Washburn RA, Smith KW, Jette AM, Janney CA (1993) The Physical Activity Scale for the Elderly (PASE): development and evaluation. J Clin Epidemiol 46:153–162PubMedCrossRefGoogle Scholar
  18. 18.
    Pahor M, Chrischilles EA, Guralnik JM, Brown SL, Wallace RB, Carbonin P (1994) Drug data coding and analysis in epidemiologic studies. Eur J Epidemiol 10:405–411PubMedCrossRefGoogle Scholar
  19. 19.
    Teng EL, Chui HC (1987) The Modified Mini-Mental State (3MS) examination. J Clin Psychiatry 48:314–318PubMedGoogle Scholar
  20. 20.
    Fried LP, Tangen CM, Walston J et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol 56:M146–M156CrossRefGoogle Scholar
  21. 21.
    Ensrud KE, Ewing SK, Cawthon PM et al (2009) A comparison of frailty indexes for the prediction of falls, disability, fractures, and mortality in older men. J Am Geriatr Soc 57:492–498PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ 3rd (1987) Psychotropic drug use and the risk of hip fracture. N Engl J Med 316:363–369PubMedCrossRefGoogle Scholar
  23. 23.
    Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Schwartz AV, Vittinghoff E, Bauer DC et al (2011) Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 305:2184–2192PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    De Rekeneire N, Resnick HE, Schwartz AV et al (2003) Diabetes is associated with subclinical functional limitation in nondisabled older individuals: the Health, Aging, and Body Composition study. Diabetes Care 26:3257–3263PubMedCrossRefGoogle Scholar
  26. 26.
    Barzilay JI, Cotsonis GA, Walston J et al (2009) Insulin resistance is associated with decreased quadriceps muscle strength in nondiabetic adults aged > or =70 years. Diabetes Care 32:736–738PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Schafer AL, Vittinghoff E, Lang TF et al (2010) Fat infiltration of muscle, diabetes, and clinical fracture risk in older adults. J Clin Endocrinol Metab 95:E368–E372PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Bazelier MT, Gallagher AM, van Staa TP et al (2012) Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs? Pharmacoepidemiol Drug Saf 21:507–514PubMedCrossRefGoogle Scholar
  29. 29.
    Monami M, Cresci B, Colombini A et al (2008) Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case-control study. Diabetes Care 31:199–203PubMedCrossRefGoogle Scholar
  30. 30.
    Huang S, Kaw M, Harris MT et al (2010) Decreased osteoclastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1. Bone 46:1138–1145PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Petit MA, Paudel ML, Taylor BC et al (2010) Bone mass and strength in older men with type 2 diabetes: the Osteoporotic Fractures in Men Study. J Bone Miner Res 25:285–291PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Yamaguchi T, Sugimoto T (2011) Bone metabolism and fracture risk in type 2 diabetes mellitus. Endocr J 58:613–624 (Review)PubMedCrossRefGoogle Scholar
  33. 33.
    Schwartz AV, Garnero P, Hillier TA et al (2009) Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab 94:2380–2386PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Ivers RQ, Cumming RG, Mitchell P, Peduto AJ, Blue Mountains Eye Study (2001) Diabetes and risk of fracture: The Blue Mountains Eye Study. Diabetes Care 24:1198–1203PubMedCrossRefGoogle Scholar
  35. 35.
    Cefalu CA, Cefalu WT (2005) Controlling hypoglycemia in type 2 diabetes: which agent for which patient? J Fam Pract 54:855–862PubMedGoogle Scholar
  36. 36.
    Kahn SE, Zinman B, Lachin JM et al (2008) Rosiglitazone associated fractures in type 2 diabetes: an analysis from ADOPT. Diabetes Care 31:845–851PubMedCrossRefGoogle Scholar
  37. 37.
    Schneider AL, Pankow JS, Heiss G, Selvin E (2012) Validity and reliability of self-reported diabetes in the atherosclerosis risk in communities study. Am J Epidemiol 176:738–743PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Margolis KL, Lihong Q, Brzyski R et al (2008) Women Health Initiative Investigators. Validity of diabetes self-reports in the Women's Health Initiative: comparison with medication inventories and fasting glucose measurements. Clin Trials 5:240–247PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Sun JK, Keenan HA, Cavallerano JD et al (2011) Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration: the Joslin 50-year medalist study. Diabetes Care 34:968–974PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Bain SC, Gill GV, Dyer PH, Jones AF et al (2003) Characteristics of type 1 diabetes of over 50 years duration (the Golden Years Cohort). Diabet Med 20:808–811PubMedCrossRefGoogle Scholar
  41. 41.
    Laing SP, Swerdlow AJ, Slater SD et al (2003) Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia 46:760–765PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Nicola Napoli
    • 1
    • 2
    Email author
  • Elsa S. Strotmeyer
    • 3
  • Kristine E. Ensrud
    • 4
    • 5
  • Deborah E. Sellmeyer
    • 6
  • Douglas C. Bauer
    • 7
  • Andrew R. Hoffman
    • 8
  • Thuy-Tien L. Dam
    • 9
  • Elizabeth Barrett-Connor
    • 9
  • Lisa Palermo
    • 7
  • Eric S. Orwoll
    • 10
  • Steven R. Cummings
    • 11
  • Dennis M. Black
    • 7
  • Ann V. Schwartz
    • 7
  1. 1.Division of Endocrinology and DiabetesUniversità Campus Bio-Medico di RomaRomeItaly
  2. 2.Division of Bone and Mineral DiseasesWashington UniversitySt LouisUSA
  3. 3.Department of Epidemiology, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  4. 4.Department of Medicine and Division of Epidemiology & Community HealthUniversity of MinnesotaMinneapolisUSA
  5. 5.Center for Chronic Disease Outcomes Research VA Health Care SystemMinneapolisUSA
  6. 6.School of MedicineJohns Hopkins UniversityBaltimoreUSA
  7. 7.University of California, San FranciscoSan FranciscoUSA
  8. 8.VA Palo Alto Health Care SystemPalo AltoUSA
  9. 9.University of California, San DiegoLa JollaUSA
  10. 10.Oregon Health & Science UniversityPortlandUSA
  11. 11.California Pacific Medical CenterSan FranciscoUSA

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