Skip to main content
Top
Published in: Diabetologia 7/2005

01-07-2005 | Article

Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk

Authors: P. Vestergaard, L. Rejnmark, L. Mosekilde

Published in: Diabetologia | Issue 7/2005

Login to get access

Abstract

Aims/hypothesis

We studied the association between fractures and type 1 and type 2 diabetes mellitus.

Methods

In this case-control study, all subjects diagnosed with a fracture (n=124,655) in Denmark served as cases, and for each case three control subjects (n=373,962) matched for sex and age were retrieved from the general population.

Results

Type 1 and type 2 diabetes were associated with an increased risk (1) of any fracture (odds ratio [OR]=1.3, 95% CI: 1.2–1.5 for type 1 diabetes and 1.2, 95% CI: 1.1–1.3 for type 2 diabetes after adjustment for confounders) and (2) of hip fractures (OR=1.7, 95% CI: 1.3–2.2 for type 1 diabetes, and 1.4, 95% CI: 1.2–1.6 for type 2 diabetes). Furthermore, type 2 diabetes was associated with a significant increase in forearm fractures (OR=1.2, 95% CI: 1.0–1.5), and type 1 diabetes was associated with an increased risk of spine fractures (OR=2.5, 95% CI: 1.3–4.6), whereas type 2 diabetes was not. Use of metformin and sulphonylureas was associated with a significantly decreased risk of any fracture, whereas a non-significant trend towards decreased risk of any fracture was associated with the use of insulin. Except for a decrease in hip fractures with use of sulphonylureas, no change in fracture risk in the hip, spine or forearm was associated with the use of insulin or oral antidiabetic drugs.

Conclusions/interpretation

Type 1 and type 2 diabetes are associated with an increased risk of any fracture and hip fractures. The use of drugs to control diabetes may reduce the association between diabetes and fractures.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bouillon R (1991) Diabetic bone disease [editorial]. Calcif Tissue Int 49:155–160PubMed Bouillon R (1991) Diabetic bone disease [editorial]. Calcif Tissue Int 49:155–160PubMed
2.
go back to reference Carnevale V, Romagnoli E, D’Erasmo E (2004) Skeletal involvement in patients with diabetes mellitus. Diabetes Metab Res Rev 20:196–204CrossRefPubMed Carnevale V, Romagnoli E, D’Erasmo E (2004) Skeletal involvement in patients with diabetes mellitus. Diabetes Metab Res Rev 20:196–204CrossRefPubMed
3.
go back to reference Raskin P, Stevenson MRM, Barilla DE, Pak CYC (1978) The hypercalciuria of diabetes mellitus: its amelioration with insulin. Clin Endocrinol 9:329–335 Raskin P, Stevenson MRM, Barilla DE, Pak CYC (1978) The hypercalciuria of diabetes mellitus: its amelioration with insulin. Clin Endocrinol 9:329–335
4.
go back to reference McNair P, Madsbad S, Christensen MS et al (1979) Bone mineral loss in insulin-treated diabetes mellitus: studies on pathogenesis. Acta Endocrinol 90:463–472PubMed McNair P, Madsbad S, Christensen MS et al (1979) Bone mineral loss in insulin-treated diabetes mellitus: studies on pathogenesis. Acta Endocrinol 90:463–472PubMed
5.
go back to reference Storm TL, Sørensen OH, Lund BJ et al (1983) Vitamin D metabolism in insulin-dependent diabetes mellitus. Metab Bone Dis Relat Res 5:107–110CrossRefPubMed Storm TL, Sørensen OH, Lund BJ et al (1983) Vitamin D metabolism in insulin-dependent diabetes mellitus. Metab Bone Dis Relat Res 5:107–110CrossRefPubMed
6.
go back to reference Nisbeth U, Lindh E, Ljunghall S, Backman U, Fellstrom B (1999) Increased fracture rate in diabetes mellitus and females after renal transplantation. Transplantation 67:1218–1222CrossRefPubMed Nisbeth U, Lindh E, Ljunghall S, Backman U, Fellstrom B (1999) Increased fracture rate in diabetes mellitus and females after renal transplantation. Transplantation 67:1218–1222CrossRefPubMed
7.
go back to reference Vogt MT, Cauley JA, Kuller LH, Nevitt MC (1997) Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res 12:283–289PubMed Vogt MT, Cauley JA, Kuller LH, Nevitt MC (1997) Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res 12:283–289PubMed
8.
go back to reference Sanada M, Taguchi A, Higashi Y et al (2004) Forearm endothelial function and bone mineral loss in postmenopausal women. Atherosclerosis 176:387–392CrossRefPubMed Sanada M, Taguchi A, Higashi Y et al (2004) Forearm endothelial function and bone mineral loss in postmenopausal women. Atherosclerosis 176:387–392CrossRefPubMed
9.
go back to reference Rix M, Andreassen H, Eskildsen P (1999) Impact of peripheral neuropathy on bone density in patients with type 1 diabetes. Diabetes Care 22:827–831PubMed Rix M, Andreassen H, Eskildsen P (1999) Impact of peripheral neuropathy on bone density in patients with type 1 diabetes. Diabetes Care 22:827–831PubMed
10.
go back to reference Ivers RQ, Mitchell P, Cumming RG, Peduto AJ (2001) Diabetes and risk of fractures—the Blue Mountains Eye Study. Diabetes Care 24:1198–1203PubMed Ivers RQ, Mitchell P, Cumming RG, Peduto AJ (2001) Diabetes and risk of fractures—the Blue Mountains Eye Study. Diabetes Care 24:1198–1203PubMed
11.
go back to reference Nabarro JD (1985) Compression fractures of the dorsal spine in hypoglycaemic fits in diabetes. Br Med J (Clin Res Ed) 291:1320 Nabarro JD (1985) Compression fractures of the dorsal spine in hypoglycaemic fits in diabetes. Br Med J (Clin Res Ed) 291:1320
12.
go back to reference De Schepper J, Smitz J, Rosseneu S, Bollen P, Louis O (1998) Lumbar spine bone mineral density in diabetic children with recent onset. Horm Res 50:193–196CrossRefPubMed De Schepper J, Smitz J, Rosseneu S, Bollen P, Louis O (1998) Lumbar spine bone mineral density in diabetic children with recent onset. Horm Res 50:193–196CrossRefPubMed
13.
go back to reference Hui SL, Epstein S, Johnston CC Jr (1985) A prospective study of bone mass in patients with type I diabetes. J Clin Endocrinol Metab 60:74–80PubMed Hui SL, Epstein S, Johnston CC Jr (1985) A prospective study of bone mass in patients with type I diabetes. J Clin Endocrinol Metab 60:74–80PubMed
14.
go back to reference Munoz-Torres M, Jodar E, Escobar-Jimenez F, Lopez-Ibarra PJ, Luna JD (1996) Bone mineral density measured by dual X-ray absorptiometry in Spanish patients with insulin-dependent diabetes mellitus. Calcif Tissue Int 58:316–319CrossRefPubMed Munoz-Torres M, Jodar E, Escobar-Jimenez F, Lopez-Ibarra PJ, Luna JD (1996) Bone mineral density measured by dual X-ray absorptiometry in Spanish patients with insulin-dependent diabetes mellitus. Calcif Tissue Int 58:316–319CrossRefPubMed
15.
go back to reference Ponder SW, McCormick DP, Fawcett HD et al (1992) Bone mineral density of the lumbar vertebrae in children and adolescents with insulin-dependent diabetes mellitus. J Pediatr 120:541–545PubMed Ponder SW, McCormick DP, Fawcett HD et al (1992) Bone mineral density of the lumbar vertebrae in children and adolescents with insulin-dependent diabetes mellitus. J Pediatr 120:541–545PubMed
16.
go back to reference Shore RM, Chesney RW, Mazess RB, Rose PG, Bargman GJ (1981) Osteopenia in juvenile diabetes. Calcif Tissue Int 33:455–457PubMed Shore RM, Chesney RW, Mazess RB, Rose PG, Bargman GJ (1981) Osteopenia in juvenile diabetes. Calcif Tissue Int 33:455–457PubMed
17.
go back to reference Tuominen JT, Impivaara O, Puukka P, Ronnemaa T (1999) Bone mineral density in patients with type 1 and type 2 diabetes. Diabetes Care 22:1196–1200PubMed Tuominen JT, Impivaara O, Puukka P, Ronnemaa T (1999) Bone mineral density in patients with type 1 and type 2 diabetes. Diabetes Care 22:1196–1200PubMed
18.
go back to reference Wiske PS, Wentworth SM, Norton JA Jr, Epstein S, Johnston CC Jr (1982) Evaluation of bone mass and growth in young diabetics. Metabolism 31:848–854CrossRefPubMed Wiske PS, Wentworth SM, Norton JA Jr, Epstein S, Johnston CC Jr (1982) Evaluation of bone mass and growth in young diabetics. Metabolism 31:848–854CrossRefPubMed
19.
go back to reference 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 86:32–38PubMed 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 86:32–38PubMed
20.
go back to reference Strotmeyer ES, Cauley JA, Schwartz AV et al (2004) Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: the health, aging, and body composition study. J Bone Miner Res 19:1084–1091PubMed Strotmeyer ES, Cauley JA, Schwartz AV et al (2004) Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: the health, aging, and body composition study. J Bone Miner Res 19:1084–1091PubMed
21.
go back to reference Barret-Connor E, Holbrook TL (1992) Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. JAMA 268:3333–3337PubMed Barret-Connor E, Holbrook TL (1992) Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. JAMA 268:3333–3337PubMed
22.
go back to reference Johnston CC Jr, Hui SL, Longcope C (1985) Bone mass and sex steroid concentration in postmenopausal Caucasian diabetics. Metabolism 34:544–550CrossRefPubMed Johnston CC Jr, Hui SL, Longcope C (1985) Bone mass and sex steroid concentration in postmenopausal Caucasian diabetics. Metabolism 34:544–550CrossRefPubMed
23.
go back to reference van Daele PL, Stolk RP, Burger H et al (1995) Bone density in non-insulin-dependent diabetes mellitus. The Rotterdam Study [see comments]. Ann Intern Med 122:409–414PubMed van Daele PL, Stolk RP, Burger H et al (1995) Bone density in non-insulin-dependent diabetes mellitus. The Rotterdam Study [see comments]. Ann Intern Med 122:409–414PubMed
24.
go back to reference Wakasugi M, Wakao R, Tawata M, Gan N, Koizumi K, Onaya T (1993) Bone mineral density measured by dual energy X-ray absorptiometry in patients with non-insulin-dependent diabetes mellitus. Bone 14:29–33CrossRefPubMed Wakasugi M, Wakao R, Tawata M, Gan N, Koizumi K, Onaya T (1993) Bone mineral density measured by dual energy X-ray absorptiometry in patients with non-insulin-dependent diabetes mellitus. Bone 14:29–33CrossRefPubMed
25.
go back to reference Weinstock RS, Goland RS, Shane E, Clemens TL, Lindsay R, Bilezikian JP (1989) Bone mineral density in women with type II diabetes mellitus. J Bone Mineral Res 4:97–101 Weinstock RS, Goland RS, Shane E, Clemens TL, Lindsay R, Bilezikian JP (1989) Bone mineral density in women with type II diabetes mellitus. J Bone Mineral Res 4:97–101
26.
go back to reference Bauer DC, Browner WS, Cauley JA et al (1993) Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group [see comments]. Ann Intern Med 118:657–665PubMed Bauer DC, Browner WS, Cauley JA et al (1993) Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group [see comments]. Ann Intern Med 118:657–665PubMed
27.
go back to reference Dennison EM, Syddall HE, Aihie SA, Craighead S, Phillips DI, Cooper C (2004) Type 2 diabetes mellitus is associated with increased axial bone density in men and women from the Hertfordshire Cohort Study: evidence for an indirect effect of insulin resistance? Diabetologia 47:1963–1968CrossRefPubMed Dennison EM, Syddall HE, Aihie SA, Craighead S, Phillips DI, Cooper C (2004) Type 2 diabetes mellitus is associated with increased axial bone density in men and women from the Hertfordshire Cohort Study: evidence for an indirect effect of insulin resistance? Diabetologia 47:1963–1968CrossRefPubMed
28.
go back to reference Forsen L, Meyer HE, Midthjell K, Edna TH (1999) Diabetes mellitus and the incidence of hip fracture: results from the Nord–Trondelag Health Survey. Diabetologia 42:920–925CrossRefPubMed Forsen L, Meyer HE, Midthjell K, Edna TH (1999) Diabetes mellitus and the incidence of hip fracture: results from the Nord–Trondelag Health Survey. Diabetologia 42:920–925CrossRefPubMed
29.
go back to reference Kelsey JL, Browner WS, Seeley DG, Nevitt MC, Cummings SR (1992) Risk factors for fractures of the distal forearm and proximal humerus. Am J Epidemiol 135:477–489PubMed Kelsey JL, Browner WS, Seeley DG, Nevitt MC, Cummings SR (1992) Risk factors for fractures of the distal forearm and proximal humerus. Am J Epidemiol 135:477–489PubMed
30.
go back to reference Melton LJ III, Achenbach SJ, O’Fallon WM, Khosla S (2002) Secondary osteoporosis and the risk of distal forearm fractures in men and women. Bone 31:119–125CrossRefPubMed Melton LJ III, Achenbach SJ, O’Fallon WM, Khosla S (2002) Secondary osteoporosis and the risk of distal forearm fractures in men and women. Bone 31:119–125CrossRefPubMed
31.
go back to reference Vogt MT, Cauley JA, Tomaino MM, Stone K, Williams JR, Herndon JH (2002) Distal radius fractures in older women: a 10-year follow-up study of descriptive characteristics and risk factors. The study of osteoporotic fractures. J Am Geriatr Soc 50:97–103CrossRefPubMed Vogt MT, Cauley JA, Tomaino MM, Stone K, Williams JR, Herndon JH (2002) Distal radius fractures in older women: a 10-year follow-up study of descriptive characteristics and risk factors. The study of osteoporotic fractures. J Am Geriatr Soc 50:97–103CrossRefPubMed
32.
go back to reference Gertner JM, Tamborlane WV, Horst RL, Sherwin RS, Felig P, Genel M (1980) Mineral metabolism in diabetes mellitus: changes accompanying treatment with portable subcutaneous insulin infusion system. J Clin Endocrinol Metab 50:862–866PubMed Gertner JM, Tamborlane WV, Horst RL, Sherwin RS, Felig P, Genel M (1980) Mineral metabolism in diabetes mellitus: changes accompanying treatment with portable subcutaneous insulin infusion system. J Clin Endocrinol Metab 50:862–866PubMed
33.
go back to reference Rothman KJ (2002) Epidemiology—an introduction. Oxford University, Oxford Rothman KJ (2002) Epidemiology—an introduction. Oxford University, Oxford
34.
go back to reference Jones S, Johansen A, Brennan J, Butler J, Lyons RA (2004) The effect of socioeconomic deprivation on fracture incidence in the United Kingdom. Osteoporosis Int 15:520–524CrossRef Jones S, Johansen A, Brennan J, Butler J, Lyons RA (2004) The effect of socioeconomic deprivation on fracture incidence in the United Kingdom. Osteoporosis Int 15:520–524CrossRef
35.
go back to reference Vestergaard P, Tigaran S, Rejnmark L, Tigaran C, Dam M, Mosekilde L (1999) Fracture risk is increased in epilepsy. Acta Neurol Scand 99:269–275PubMed Vestergaard P, Tigaran S, Rejnmark L, Tigaran C, Dam M, Mosekilde L (1999) Fracture risk is increased in epilepsy. Acta Neurol Scand 99:269–275PubMed
36.
go back to reference Jones G, Nguyen T, Sambrook PN, Eisman JA (1995) Thiazide diuretics and fractures: can meta-analysis help? J Bone Miner Res 10:106–111PubMed Jones G, Nguyen T, Sambrook PN, Eisman JA (1995) Thiazide diuretics and fractures: can meta-analysis help? J Bone Miner Res 10:106–111PubMed
37.
go back to reference Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ III (1987) Psychotropic drug use and the risk of hip fracture. N Engl J Med 316:363–369PubMed Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ III (1987) Psychotropic drug use and the risk of hip fracture. N Engl J Med 316:363–369PubMed
38.
go back to reference Ensrud KE, Blackwell T, Mangione CM et al (2003) Central nervous system active medications and risk for fractures in older women. Arch Intern Med 163:949–957PubMed Ensrud KE, Blackwell T, Mangione CM et al (2003) Central nervous system active medications and risk for fractures in older women. Arch Intern Med 163:949–957PubMed
39.
go back to reference Andersen TF, Madsen M, Jørgensen J, Mellemkjær L, Olsen JH (1999) The Danish national hospital register. Dan Med Bull 46:263–268PubMed Andersen TF, Madsen M, Jørgensen J, Mellemkjær L, Olsen JH (1999) The Danish national hospital register. Dan Med Bull 46:263–268PubMed
40.
go back to reference Munk-Jørgensen P, Mortensen PB (1997) The Danish psychiatric central register. Dan Med Bull 44:82–84PubMed Munk-Jørgensen P, Mortensen PB (1997) The Danish psychiatric central register. Dan Med Bull 44:82–84PubMed
41.
go back to reference Mosbech J, Jørgensen J, Madsen M, Rostgaard K, Thornberg K, Poulsen TD (1995) The Danish national patient register: evaluation of data quality. Ugeskr Læger 157:3741–3745PubMed Mosbech J, Jørgensen J, Madsen M, Rostgaard K, Thornberg K, Poulsen TD (1995) The Danish national patient register: evaluation of data quality. Ugeskr Læger 157:3741–3745PubMed
42.
go back to reference Vestergaard P, Mosekilde L (2002) Fracture risk in patients with celiac disease, Crohn’s disease, and ulcerative colitis: a nation-wide follow-up study in 16,416 patients in Denmark. Am J Epidemiol 156:1–10CrossRefPubMed Vestergaard P, Mosekilde L (2002) Fracture risk in patients with celiac disease, Crohn’s disease, and ulcerative colitis: a nation-wide follow-up study in 16,416 patients in Denmark. Am J Epidemiol 156:1–10CrossRefPubMed
43.
go back to reference Vestergaard P, Emborg C, Støving RK, Hagen C, Mosekilde L, Brixen K (2002) Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders—a nation-wide register study. Int J Eating Disord 32:301–308CrossRef Vestergaard P, Emborg C, Støving RK, Hagen C, Mosekilde L, Brixen K (2002) Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders—a nation-wide register study. Int J Eating Disord 32:301–308CrossRef
44.
go back to reference STATA (2003) STATA statistical software: release 8.0. STATA Corp., College Station, TX STATA (2003) STATA statistical software: release 8.0. STATA Corp., College Station, TX
45.
go back to reference Hemenway D, Colditz GA, Willett WC, Stampfer MJ, Speizer FE (1988) Fractures and lifestyle: effect of cigarette smoking, alcohol intake, and relative weight on the risk of hip and forearm fractures in middle-aged women. Am J Public Health 78:1554–1558PubMed Hemenway D, Colditz GA, Willett WC, Stampfer MJ, Speizer FE (1988) Fractures and lifestyle: effect of cigarette smoking, alcohol intake, and relative weight on the risk of hip and forearm fractures in middle-aged women. Am J Public Health 78:1554–1558PubMed
46.
go back to reference Clowes JA, Allen HC, Prentis DM, Eastell R, Blumsohn A (2003) Octreotide abolishes the acute decrease in bone turnover in response to oral glucose. J Clin Endocrinol Metab 88:4867–4873CrossRefPubMed Clowes JA, Allen HC, Prentis DM, Eastell R, Blumsohn A (2003) Octreotide abolishes the acute decrease in bone turnover in response to oral glucose. J Clin Endocrinol Metab 88:4867–4873CrossRefPubMed
47.
go back to reference Follak N, Klöting I, Wolf E, Merk H (2004) Improving metabolic control reverses the histomorphometric and biomechanical abnormalities of an experimentally induced bone deficit in spontaneously diabetic rats. Calcif Tissue Int 74:551–560CrossRefPubMed Follak N, Klöting I, Wolf E, Merk H (2004) Improving metabolic control reverses the histomorphometric and biomechanical abnormalities of an experimentally induced bone deficit in spontaneously diabetic rats. Calcif Tissue Int 74:551–560CrossRefPubMed
48.
go back to reference Moyer-Mileur LJ, Dixon SB, Quick JL, Askew EW, Murray MA (2004) Bone mineral acquisition in adolescents with type 1 diabetes. J Pediatr 145:662–669CrossRefPubMed Moyer-Mileur LJ, Dixon SB, Quick JL, Askew EW, Murray MA (2004) Bone mineral acquisition in adolescents with type 1 diabetes. J Pediatr 145:662–669CrossRefPubMed
Metadata
Title
Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk
Authors
P. Vestergaard
L. Rejnmark
L. Mosekilde
Publication date
01-07-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1786-3

Other articles of this Issue 7/2005

Diabetologia 7/2005 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.