Osteoporosis International

, Volume 26, Issue 1, pp 85–91 | Cite as

Ankylosing spondylitis confers substantially increased risk of clinical spine fractures: a nationwide case-control study

  • D. Prieto-Alhambra
  • J. Muñoz-Ortego
  • F. De Vries
  • D. Vosse
  • N. K. Arden
  • P. Bowness
  • C. Cooper
  • A. Diez-Perez
  • P. VestergaardEmail author
Original Article



Ankylosing spondylitis (AS) leads to osteopenia/osteoporosis and spine rigidity. We conducted a case-control study and found that AS-affected patients have a 5-fold and 50 % increased risk of clinical spine and all clinical fractures, respectively. Excess risk of both is highest in the first years and warrants an early bone health assessment after diagnosis.


Ankylosing spondylitis (AS) is related to spine rigidity and reduced bone mass, but data on its impact on fracture risk are scarce. We aimed to study the association between AS and clinical fractures using a case-control design.


From the Danish Health Registries, we identified all subjects who sustained a fracture in the year 2000 (cases) and matched up to three controls by year of birth, gender and region. Clinically diagnosed AS was identified using International Classification of Diseases, 8th revision (ICD-8; 71249), and International Classification of Diseases, 10th revision (ICD-10; M45) codes. We also studied the impact of AS duration. Conditional logistic regression was used to estimate crude and adjusted odds ratios (ORs) for non-traumatic fractures (any site, clinical spine and non-vertebral) according to AS status and time since AS diagnosis. Multivariate models were adjusted for fracture history, socio-economic status, previous medical consultations, alcoholism and use of oral glucocorticoids.


We identified 139/124,655 (0.11 %) AS fracture cases, compared to 271/373,962 (0.07 %) AS controls. Unadjusted (age- and gender-matched) odds ratio (OR) were 1.54 [95 % confidence interval (95 %CI) 1.26–1.89] for any fracture, 5.42 [2.50–11.70] for spine and 1.39 [1.12–1.73] for non-vertebral fracture. The risk peaked in the first 2.5 years following AS diagnosis: OR 2.69 [1.84–3.92] for any fracture.


Patients with AS have a 5-fold higher risk of clinical spine fracture and a 35 % increased risk of non-vertebral fracture. This excess risk peaks early, in the first 2.5 years of AS disease. Patients should be assessed for fracture risk early after AS diagnosis.


Ankylosing Bone Electronic health records Epidemiology Fractures Spondylitis 



Statistics Denmark is acknowledged for the help with the acquisition of the data.


DPA, NKA and CC receive partial funding from the Oxford NIHR Musculoskeletal Biomedical Research Unit. DPA receives partial funding from the MRC Lifecourse Epidemiology Unit (Southampton), the IDIAP Jordi Gol Primary Care Research Institute and the URFOA (IMIM, Parc de Salut Mar, Barcelona). DPA receives funding from the NIHR Clinician Scientist Award scheme.

The data retrieval was sponsored by a grant from the Danish Medical Research Council (Grant number 22-04-0495).

Conflicts of interest



  1. 1.
    Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleit M, Distler A, Sieper J (1998) Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 41:58–67PubMedCrossRefGoogle Scholar
  2. 2.
    van der Linden SM, Valkenburg HA, de Jongh BM, Cats A (1984) The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum 27:241–249PubMedCrossRefGoogle Scholar
  3. 3.
    Westerveld LA, Verlaan JJ, Oner FC (2009) Spinal fractures in patients with ankylosing spinal disorders: a systematic review of the literature on treatment, neurological status and complications. Eur Spine J 18:145–156PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Sieper J, Appel H, Braun J, Rudwaleit M (2008) Critical appraisal of assessment of structural damage in ankylosing spondylitis: implications for treatment outcomes. Arthritis Rheum 58:649–656PubMedCrossRefGoogle Scholar
  5. 5.
    Graham B, Van Peteghem PK (1989) Fractures of the spine in ankylosing spondylitis. Diagnosis, treatment, and complications. Spine (Phila Pa 1976) 14:803–807CrossRefGoogle Scholar
  6. 6.
    Fox MW, Onofrio BM, Kilgore JE (1993) Neurological complications of ankylosing spondylitis. J Neurosurg 78:871–878PubMedCrossRefGoogle Scholar
  7. 7.
    Tyroch AH, McGuire EL, McLean SF, Kozar RA, Gates KA, Kaups KL, Cook C, Cowgill SM, Griswold JA, Sue LA, Craun ML, Price J (2005) The association between Chance fractures and intra-abdominal injuries revisited: a multicenter review. Am Surg 71:434–438PubMedGoogle Scholar
  8. 8.
    Vosse D, Feldtkeller E, Erlendsson J, Geusens P, van der Linden S (2004) Clinical vertebral fractures in patients with ankylosing spondylitis. J Rheumatol 31:1981–1985PubMedGoogle Scholar
  9. 9.
    Donnelly S, Doyle DV, Denton A, Rolfe I, McCloskey EV, Spector TD (1994) Bone mineral density and vertebral compression fracture rates in ankylosing spondylitis. Ann Rheum Dis 53:117–121PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Cooper C, Carbone L, Michet CJ, Atkinson EJ, O’Fallon WM, Melton LJ 3rd (1994) Fracture risk in patients with ankylosing spondylitis: a population based study. J Rheumatol 21:1877–1882PubMedGoogle Scholar
  11. 11.
    Ralston SH, Urquhart GD, Brzeski M, Sturrock RD (1990) Prevalence of vertebral compression fractures due to osteoporosis in ankylosing spondylitis. BMJ 300:563–565PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Vosse D, Landewe R, van der Heijde D, van der Linden S, van Staa TP, Geusens P (2009) Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case-control study. Ann Rheum Dis 68:1839–1842PubMedCrossRefGoogle Scholar
  13. 13.
    Montala N, Juanola X, Collantes E, Munoz-Gomariz E, Gonzalez C, Gratacos J, Zarco P, Sueiro JL, Mulero J, Torre-Alonso JC, Batlle E, Carmona L (2011) Prevalence of vertebral fractures by semiautomated morphometry in patients with ankylosing spondylitis. J RheumatolGoogle Scholar
  14. 14.
    Delmas PD, van de Langerijt L, Watts NB, Eastell R, Genant H, Grauer A, Cahall DL (2005) Underdiagnosis of vertebral fractures is a worldwide problem: the IMPACT study. J Bone Miner Res 20:557–563PubMedCrossRefGoogle Scholar
  15. 15.
    Arends S, Spoorenberg A, Bruyn GA, Houtman PM, Leijsma MK, Kallenberg CG, Brouwer E, van der Veer E (2011) The relation between bone mineral density, bone turnover markers, and vitamin D status in ankylosing spondylitis patients with active disease: a cross-sectional analysis. Osteoporos Int 22:1431–1439PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Franck H, Meurer T, Hofbauer LC (2004) Evaluation of bone mineral density, hormones, biochemical markers of bone metabolism, and osteoprotegerin serum levels in patients with ankylosing spondylitis. J Rheumatol 31:2236–2241PubMedGoogle Scholar
  17. 17.
    Will R, Palmer R, Bhalla AK, Ring F, Calin A (1989) Osteoporosis in early ankylosing spondylitis: a primary pathological event? Lancet 2:1483–1485PubMedCrossRefGoogle Scholar
  18. 18.
    van der Weijden MA, van der Horst-Bruinsma IE, van Denderen JC, Dijkmans BA, Heymans MW, Lems WF (2012) High frequency of vertebral fractures in early spondylarthropathies. Osteoporos Int 23:1683–1690PubMedCrossRefGoogle Scholar
  19. 19.
    van der Weijden MA, Claushuis TA, Nazari T, Lems WF, Dijkmans BA, van der Horst-Bruinsma IE (2012) High prevalence of low bone mineral density in patients within 10 years of onset of ankylosing spondylitis: a systematic review. Clin RheumatolGoogle Scholar
  20. 20.
    Muñoz-Ortego J, Vestergaard P, Blanch J, Wordswoth P, Judge A, Kassim M, Arden N, Cooper C, Díez-Perez A, Prieto-Alhambra D (2012) Ankylosing spondylitis is associated with an increased risk of osteoporotic fractures: a population-based cohort study. Arthritis Rheum 64Google Scholar
  21. 21.
    Muñoz-Ortego J, Vestergaard P, Rubio JB, Wordsworth P, Judge A, Javaid MK, Arden NK, Cooper C, Diez-Perez A, Prieto-Alhambra D (2014) Ankylosing spondylitis is associated with an increased risk of vertebral and non-vertebral clinical fractures: a population-based cohort study. J Bone Miner Res 29(8):1770–1776PubMedCrossRefGoogle Scholar
  22. 22.
    Frank L (2000) Epidemiology. When an entire country is a cohort. Science 287:2398–2399PubMedCrossRefGoogle Scholar
  23. 23.
    Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L, Olsen JH (1999) The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull 46:263–268PubMedGoogle Scholar
  24. 24.
    Mosbech J, Jorgensen J, Madsen M, Rostgaard K, Thornberg K, Poulsen TD (1995) The national patient registry. Evaluation of data quality. Ugeskr Laeger 157:3741–3745PubMedGoogle Scholar
  25. 25.
    Vestergaard P, Mosekilde L (2002) Fracture risk in patients with celiac disease, Crohn’s disease, and ulcerative colitis: a nationwide follow-up study of 16,416 patients in Denmark. Am J Epidemiol 156:1–10PubMedCrossRefGoogle Scholar
  26. 26.
    Wacholder S, McLaughlin JK, Silverman DT, Mandel JS (1992) Selection of controls in case-control studies. I. Principles. Am J Epidemiol 135:1019–1028PubMedGoogle Scholar
  27. 27.
    Munk-Jorgensen P, Mortensen PB (1997) The Danish Psychiatric Central Register. Dan Med Bull 44:82–84PubMedGoogle Scholar
  28. 28.
    Wanders A, Heijde D, Landewe R, Behier JM, Calin A, Olivieri I, Zeidler H, Dougados M (2005) Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum 52:1756–1765PubMedCrossRefGoogle Scholar
  29. 29.
    Kang KY, Ju JH, Park SH, Kim HY (2013) The paradoxical effects of TNF inhibitors on bone mineral density and radiographic progression in patients with ankylosing spondylitis. Rheumatology (Oxford) 52:718–726CrossRefGoogle Scholar
  30. 30.
    Kang KY, Lee KY, Kwok SK, Ju JH, Park KS, Hong YS, Kim HY, Park SH (2011) The change of bone mineral density according to treatment agents in patients with ankylosing spondylitis. Joint Bone Spine 78:188–193PubMedCrossRefGoogle Scholar
  31. 31.
    Mathieu S, Gossec L, Dougados M, Soubrier M (2011) Cardiovascular profile in ankylosing spondylitis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken) 63:557–563CrossRefGoogle Scholar
  32. 32.
    Quismorio FP Jr (2006) Pulmonary involvement in ankylosing spondylitis. Curr Opin Pulm Med 12:342–345PubMedCrossRefGoogle Scholar
  33. 33.
    Khedr EM, Rashad SM, Hamed SA, El-Zharaa F, Abdalla AK (2009) Neurological complications of ankylosing spondylitis: neurophysiological assessment. Rheumatol Int 29:1031–1040PubMedCrossRefGoogle Scholar
  34. 34.
    Leirisalo-Repo M, Turunen U, Stenman S, Helenius P, Seppala K (1994) High frequency of silent inflammatory bowel disease in spondylarthropathy. Arthritis Rheum 37:23–31PubMedCrossRefGoogle Scholar
  35. 35.
    Gratacos J, Collado A, Sanmarti R, Poch E, Torras A, Munoz-Gomez J (1993) Coincidental amyloid nephropathy and IgA glomerulonephritis in a patient with ankylosing spondylitis. J Rheumatol 20:1613–1615PubMedGoogle Scholar
  36. 36.
    Andersen T, Madsen M, Jørgensen J, Mellemkjær L, Olsen J (1999) The Danish National Hospital Register. Dan Med Bull 46:263–268PubMedGoogle Scholar
  37. 37.
    Mosbech J, Jørgensen J, Madsen M, Rostgaard K, Thornberg K, Poulsen T (1995) The Danish National Patient Register: evaluation of data quality. Ugeskr Laeger 157:3741–3745PubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2014

Authors and Affiliations

  • D. Prieto-Alhambra
    • 1
    • 2
    • 3
    • 4
  • J. Muñoz-Ortego
    • 5
  • F. De Vries
    • 2
    • 6
    • 7
  • D. Vosse
    • 8
  • N. K. Arden
    • 1
    • 2
  • P. Bowness
    • 1
  • C. Cooper
    • 1
    • 2
  • A. Diez-Perez
    • 3
  • P. Vestergaard
    • 9
    • 10
    Email author
  1. 1.Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal SciencesUniversity of OxfordOxfordUK
  2. 2.MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK
  3. 3.URFOA-IMIM and RETICEFParc de Salut Mar and Instituto de Salud Carlos IIIBarcelonaSpain
  4. 4.GREMPAL Research Group, IDIAP Jordi Gol Primary Care Research InstituteUniversitat Autònoma de BarcelonaBarcelonaSpain
  5. 5.Rheumatology DepartmentHospital Universitari Sagrat CorBarcelonaSpain
  6. 6.Department of Clinical Pharmacy and ToxicologyMaastricht University Medical CentreMaastrichtThe Netherlands
  7. 7.Utrecht Institute for Pharmaceutical SciencesUniversiteit UtrechtUtrechtThe Netherlands
  8. 8.Department of Internal Medicine, Division of RheumatologyMaastricht University Medical CentreMaastrichtThe Netherlands
  9. 9.Aalborg University HospitalAalborg UniversityAalborgDenmark
  10. 10.Department of EndocrinologyAalborg HospitalAalborgDenmark

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