Skip to main content

Advertisement

SpringerLink
Log in

Hypertension Is a Risk Factor for Fractures

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

To study the effects of hypertension and other cardiovascular risk factors on risk of fractures, we carried out a case-control study including 124,655 fracture cases and 373,962 age- and gender-matched controls. The main exposure was hypertension, stroke, acute myocardial infarction, ischemic heart disease, atrial fibrillation, peripheral arterial disease, and deep venous thromboembolism, and the main confounders were use of diuretics, antihypertensive drugs, organic nitrates, vitamin K antagonists, and cholesterol lowering drugs along with other confounders. Hypertension and stroke were the only significant risk factors in both the short-term (OR = 1.27, 95% CI = 1.20–1.34 and 1.24, and 95% CI = 1.16–1.31 for ≤3 years since diagnosis of hypertension and stroke, respectively) and the long-term (OR = 1.11, 95% CI = 1.00–1.23 and 1.09, and 95% CI = 1.02–1.18 for > 6 years since diagnosis of hypertension and stroke, respectively) perspective. Acute myocardial infarction, atrial fibrillation, and deep venous thromboembolism were all associated with a transient increase in the risk of fractures within the first 3 years following diagnosis. Peripheral arterial disease and ischemic heart disease were not associated with an increased risk of fractures. In conclusion, hypertension and stroke seem to be the major cardiovascular risk factors for fractures, whereas acute myocardial infarction, atrial fibrillation, and deep venous thromboembolism seem to be only minor risk factors. The fracture risk in hypertension may explain why antihypertensive drugs as a class effect are associated with a decreased risk of fractures. These drugs may counter some of the deleterious effects of high blood pressure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rejnmark L, Vestergaard P, Mosekilde L (2006) Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. J Hypertension 24:581–589

    Article  CAS  Google Scholar 

  2. Tanko LB, Bagger YZ, Christiansen C (2003) Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif Tissue Int 73:15–20

    Article  PubMed  CAS  Google Scholar 

  3. Cappuccio F, Meilahn E, Zmuda J et al (1999) High blood pressure and bone-mineral loss in elderly white women:a prospective study. Study of Osteoporotic Fractures Research Group. Lancet 354:971–975

    CAS  Google Scholar 

  4. McCarron D, Pingree P, Rubin R et al (1980) Enhanced parathyroid function in essential hypertension: a homeostatic response to a urinary calcium leak. Hypertension 2:162–168

    PubMed  CAS  Google Scholar 

  5. Rejnmark L, Vestergaard P, Heickendorff L et al (2001) Effects of thiazide- and loop-diuretics, alone or in combination, on calciotropic hormones and biochemical bone markers: a randomized controlled study. J Intern Med 250:144–150

    Article  PubMed  CAS  Google Scholar 

  6. Rejnmark L, Vestergaard P, Mosekilde L (2005) Reduced fracture risk in users of thiazide diuretics. Calcif Tissue Int 76:167–175

    Article  PubMed  CAS  Google Scholar 

  7. Marcovitz PA, Tran HH, Franklin BA et al (2005) Usefulness of bone mineral density to predict significant coronary artery disease. Am J Cardiol 96:1059–1063

    Article  PubMed  Google Scholar 

  8. Rejnmark L, Vestergaard P, Mosekilde L (2006) Decreased fracture risk in users of organic nitrates:a nationwide case-control study. J Bone Miner Res 21:1811–1817

    Article  PubMed  CAS  Google Scholar 

  9. Bauer D (2003) HMG CoA reductase inhibitors and the skeleton: a comprehensive review. Osteoporosis Int 14:273–282

    Article  CAS  Google Scholar 

  10. Meier C, Schlienger R, Kraenzlin M et al (2000) HMG-CoA reductase inhibitors and the risk of fracture. JAMA 283:3205–3210

    Article  PubMed  CAS  Google Scholar 

  11. Wang P, Solomon D, Mogun H et al (2000) HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. JAMA 283:3211–3216

    Article  PubMed  CAS  Google Scholar 

  12. Luckman S, Hughes D, Coxon F et al (1998) Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 13:581–589

    Article  PubMed  CAS  Google Scholar 

  13. Rejnmark L, Vestergaard P, Mosekilde L (2006) Statin but not non-statin lipid-lowering drugs decrease fracture risk:a nation-wide case-control study. Calcif Tissue Int 79:27–36

    Article  PubMed  CAS  Google Scholar 

  14. Rejnmark L, Vestergaard P, Mosekilde L (2006) Fracture risk in patients treated with amiodarone or digoxin for cardiac arrhythmias: a nation-wide case-control study. Osteoporos Int 18:409–417

    Article  PubMed  CAS  Google Scholar 

  15. Vestergaard P, Emborg C, Støving R et al (2002) Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders—a nation-wide register study. Int J Eat Disord 32:301–308

    Article  PubMed  Google Scholar 

  16. Andersen T, Madsen M, Jørgensen J et al (1999) The Danish National Hospital Register. Danish Med Bull 46:263–268

    PubMed  CAS  Google Scholar 

  17. Mosbech J, Jørgensen J, Madsen M et al (1995) The Danish National Patient Register: evaluation of data quality. Ugeskr Laeger 157:3741–3745

    PubMed  CAS  Google Scholar 

  18. Vestergaard P, Rejnmark L, Mosekilde L (2004) Fracture risk associated with use of anti-epileptic drugs. Epilepsia 45:1330–1337

    Article  PubMed  CAS  Google Scholar 

  19. Vestergaard P, Rejnmark L, Mosekilde L (2006) Socioeconomic aspects of fractures within universal public healthcare: a nationwide case-control study from Denmark. Scand J Public Health 34:371–377

    Article  PubMed  Google Scholar 

  20. Kanis J, Johansson H, Johnell O et al (2005) Alcohol intake as a risk factor for fracture. Osteoporosis Int 16:737–742

    Article  Google Scholar 

  21. Klotzbuecher C, Ross P, Landsman P et al (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the litterature and statistical synthesis. J Bone Miner Res 15:721–739

    Article  PubMed  CAS  Google Scholar 

  22. Munk-Jørgensen P, Mortensen P (1997) The Danish Psychiatric Central Register. Danish Med Bull 44:82–84

    PubMed  Google Scholar 

  23. 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 156:1–10

    Article  PubMed  Google Scholar 

  24. Krarup L, Boysen G, Janjua H et al (2007) Validity of stroke diagnoses in a National Register of Patients. Neuroepidemiology 28:150–154

    Article  PubMed  Google Scholar 

  25. Madsen M, Balling H, Eriksen L (1990) The validity of the diagnosis of acute myocardial infarction in 2 registries: the Heart Registry compared to the National Patient Registry. Ugeskr Laeger 152:308–314

    PubMed  CAS  Google Scholar 

  26. Nielsen HW, Tüchsen F, Jensen MV (1996) Validity of the diagnosis “essential hypertension” in the National Patient Registry. Ugeskr Laeger 158:163–167

    PubMed  CAS  Google Scholar 

  27. Cirillo M, Galletti F, Corrado M et al (1986) Disturbances of renal and erythrocyte calcium handling in rats of the Milan hypertensive strain. J Hypertens 4:443–449

    Article  PubMed  CAS  Google Scholar 

  28. Cirillo M, Galletti F, Strazzullo P et al (1989) On the pathogenetic mechanism of hypercalciuria in genetically hypertensive rats of the Milan strain. Am J Hypertens 2:741–746

    PubMed  CAS  Google Scholar 

  29. Cirillo M, Strazzullo P, Galletti F et al (1985) The effect of an intravenous calcium load on serum total and ionized calcium in normotensive and hypertensive subjects. J Clin Hypertens 1:30–34

    PubMed  CAS  Google Scholar 

  30. Strazzullo P, Cappuccio F, De Leo A et al (1987) Calcium metabolism and blood pressure in children. J Hum Hypertens 1:155–159

    PubMed  CAS  Google Scholar 

  31. Strazzullo P, Galletti F, Cirillo M et al (1986) Altered extracellular calcium homoeostasis in essential hypertension: a consequence of abnormal cell calcium handling. Clin Sci (Lond) 71:239–244

    CAS  Google Scholar 

  32. Strazzullo P, Galletti F, Siani A et al (1984) Altered kinetics of an intravenous calcium load in hypertensive patients. J Hypertens 2(3, Suppl 2): S499–S501

    CAS  Google Scholar 

  33. Strazzullo P, Nunziata V, Cirillo M et al (1983) Abnormalities of calcium metabolism in essential hypertension. Clin Sci 65:137–141

    PubMed  CAS  Google Scholar 

  34. Strazzullo P, Siani A, Gugliemi S et al (1986) Controlled trial of long-term oral calcium supplementation in essential hypertension. Hypertension 8:1084–1088

    PubMed  CAS  Google Scholar 

  35. Rejnmark L, Vestergaard P, Mosekilde L (2006) Fracture risk in patients treated with loop diuretics. J Inter Med 259:117–124

    Article  CAS  Google Scholar 

  36. Keenan M, Perry J, Jordan C (1984) Factors affecting balance and ambulation following stroke. Clin Orthop Rel Res 182:165–171

    Google Scholar 

  37. Melton L III, Brown R Jr, Achenbach S et al (2001) Long-term fracture risk following ischemic stroke: a population-based study. Osteoporosis Int 19:980–986

    Article  Google Scholar 

  38. Poplinger A, Pillar T (1985) Hip fracture in stroke patients: epidemiology and rehabilitation. Acta Orthop Scand 56:226–227

    Article  Google Scholar 

  39. Ramnemark A, Nyberg L, Borss B et al (1998) Fractures after stroke. Osteoporosis Int 8:92–95

    Article  CAS  Google Scholar 

  40. Browner W, Pressman A, Nevitt M et al (1993) Association between low bone density and stroke in elderly women. The study of osteoporotic fractures. Stroke 24:940–946

    CAS  Google Scholar 

  41. Hamdy R, Krishnaswamy G, Cancellaro V et al (1993) Changes in bone mineral content and density after stroke. Am J Phys Med Rehab 72:188–191

    Article  CAS  Google Scholar 

  42. Hamdy R, Moore S, Cancellaro V et al (1995) Long-term effects of strokes on bone mass. Am J Phys Med Rehab 74:351–356

    CAS  Google Scholar 

  43. Jorgensen L, Jacobsen B, Wilsgaard T et al (2000) Walking after stroke: Does it matter? Changes in bone mineral density within the first 12 months after stroke. A longitudinal study. Osteoporosis Int 11:381–387

    CAS  Google Scholar 

  44. Liu M, Tsuji T, Higuchi Y et al (1999) Osteoporosis in hemiplegic stroke patients as studied with dual-energy X-ray absorptiometry. Arch Phys Med Rehab 80:1219–1226

    Article  CAS  Google Scholar 

  45. Ramnemark A, Nyberg L, Lorentzon R et al (1999) Progressive hemiosteoporosis on the paretic side and increased bone mineral density in the nonparetic arm the first year after severe stroke. Osteoporosis Int 9:269–275

    Article  CAS  Google Scholar 

  46. Sahin L, Zoran K et al (2001) Bone mineral density in patients with stroke. Am J Phys Med Rehab 80:592–596

    Article  CAS  Google Scholar 

  47. Sato Y, Fujimatsu Y, Kikuyama M et al (1998) Influence of immobilization on bone mass and bone metabolism in hemiplegic elderly patients with a long-standing stroke [comment]. J Neurol Sci 156:205–210

    Article  PubMed  CAS  Google Scholar 

  48. Christiansen C, Christensen M, McNair P et al (1980) Prevention of early bone postmenopausal loss: controlled 2-year study in 315 normal females. Eur J Clin Invest 10:273–279

    Article  PubMed  CAS  Google Scholar 

  49. Greendale G, Lee N, Arriola E (1999) The menopause. Lancet 353:571–580

    Article  PubMed  CAS  Google Scholar 

  50. Vestergaard P, Hermann A, Stilgren L et al (2003) Effects of 5 years of hormonal replacement therapy on menopausal symptoms and blood pressure: a randomised controlled study. Maturitas 46:123–132

    Article  PubMed  CAS  Google Scholar 

  51. Jenkins D, Cochran T (1969) Osteoporosis: the dramatic effect of disuse of an extremity. Clin Orthop 64:128–134

    PubMed  CAS  Google Scholar 

  52. Abramson A, Delagi E (1961) Influence of weight-bearing and muscle contraction on disuse osteoporosis. Arch Phys Med Rehab 42:147–151

    CAS  Google Scholar 

  53. Vestergaard P, Rejnmark L, Mosekilde L (2005) Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48:1292–1299

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The Danish Medical Research Council granted financial support for this study (Grant 22–04-0495). Danmarks Statistik (Statistics Denmark) is acknowledged for their help, without which this project would not have been possible. Research Librarian Ms. Edith Clausen is acknowledged for invaluable help with the references.

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism C, The Osteoporosis Clinic, Aarhus Amtssygehus, Aarhus University Hospital, Tage Hansens Gade 2, 8000, Aarhus C, Denmark

    Peter Vestergaard, Lars Rejnmark & Leif Mosekilde

Authors
  1. Peter Vestergaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lars Rejnmark
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leif Mosekilde
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Vestergaard.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vestergaard, P., Rejnmark, L. & Mosekilde, L. Hypertension Is a Risk Factor for Fractures. Calcif Tissue Int 84, 103–111 (2009). https://doi.org/10.1007/s00223-008-9198-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-008-9198-2

Keywords

Search

Navigation