Skip to main content

Advertisement

Log in

Bone Mineral Density and Fracture Risk in Ankylosing Spondylitis: A Meta-Analysis

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

We conducted a meta-analysis of studies to examine the risk of vertebral and non-vertebral fractures in patients with ankylosing spondylitis (AS). Additionally, we evaluated the risk factors of vertebral fractures in AS. Two authors independently searched Embase and Medline for studies that had assessed the risk of fractures in patients with AS. Twenty-two studies were eligible for the meta-analysis. Patients with AS had high frequency of vertebral fractures [OR (95% CI): 1.96 (1.52–2.51)]. Major risk factors for vertebral fractures in patients with AS include low BMD at the femoral neck and total hip, male gender, longer disease duration, higher BASDAI, higher BASRI, and possibly inflammatory bowel disease. The risk of non-vertebral fractures [OR (95% CI) 1.10 (1.04–1.15)] was 10% higher in AS patients than in controls. The risk of hip fractures in AS patients was not statistically significant [OR (95% CI) 1.17 (0.71–1.92)] in our pooled analysis. We found that patients with AS are at high risk of vertebral fractures. Male sex, duration of AS, mSASSS, BASRI, and low BMD at the hip and distal forearm were associated with the risk of vertebral fractures. Current evidence on the risk of hip fractures in patients with AS is inconsistent. Data about the effect of NSAIDs and TNF inhibitors on fracture risk in AS are limited.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Haroon N, Inman RD (2010) Ankylosing spondylitis—new criteria, new treatments. Bull NYU Hosp Jt Dis 68(3):171–174

    PubMed  Google Scholar 

  2. Haroon NN, Paterson JM, Li P, Haroon N (2014) Increasing proportion of female patients with ankylosing spondylitis: a population-based study of trends in the incidence and prevalence of AS. BMJ Open 4(12):e006634

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lories RJ, Haroon N (2014) Bone formation in axial spondyloarthritis. Best Pract Res Clin Rheumatol 28(5):765–777

    Article  PubMed  Google Scholar 

  4. Stolwijk C, van Tubergen A, Castillo-Ortiz JD, Boonen A (2015) Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum Dis 74(1):65–73

    Article  PubMed  Google Scholar 

  5. Davey-Ranasinghe N, Deodhar A (2013) Osteoporosis and vertebral fractures in ankylosing spondylitis. Curr Opin Rheumatol 25(4):509–516

    Article  PubMed  Google Scholar 

  6. 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 Rheumatol 31(11):1529–1535

    Article  PubMed  PubMed Central  Google Scholar 

  7. Feldtkeller E, Vosse D, Geusens P, van der Linden S (2006) Prevalence and annual incidence of vertebral fractures in patients with ankylosing spondylitis. Rheumatol Int 26:234–239

    Article  PubMed  Google Scholar 

  8. Schiefer TK, Milligan BD, Bracken CD, Jacob JT, Krauss WE, Pichelmann MA, Clarke MJ (2014) In-hospital neurologic deterioration following fractures of the ankylosed spine: a single-institution experience. World Neurosurg 83(5):775–783

  9. Ralston SM, Urquhart GD, Brezeski M, Sturrock RD (1990) Prevalence of vertebral compression fractures due to osteoporosis in ankylosing spondylitis. Br Med J 300:563–565

    Article  CAS  Google Scholar 

  10. Sapkas G, Kateros K, Papadakis SA, Galanakos S, Brilakis E, Machairas G, Katonis P (2009) Surgical outcome after spinal fractures in patients with ankylosing spondylitis. BMC Musculoskelet Disord 10:96

    Article  PubMed  PubMed Central  Google Scholar 

  11. Clayton ES, Hochberg MC (2013) Osteoporosis and osteoarthritis, rheumatoid arthritis and spondylarthropathies. Curr Osteoporos Rep 11(4):257–262

    Article  PubMed  Google Scholar 

  12. Montala N, Juanola X, Collantes E, Munoz-Gomariz E, Gonzalez C, Gratacos J, Zarco P, Fernandez 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 Rheumatol 38:893–897

    Article  PubMed  Google Scholar 

  13. 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):1770–1776

    Article  PubMed  Google Scholar 

  14. Vosse D, Landewé 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(12):1839–1842

    Article  CAS  PubMed  Google Scholar 

  15. Weiss RJ, Wick MC, Ackermann PW, Montgomery SM (2010 Nov) Increased fracture risk in patients with rheumatic disorders and other inflammatory diseases – a case-control study with 53,108 patients with fracture. J Rheumatol 37(11):2247–2250

    Article  PubMed  Google Scholar 

  16. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535

    Article  PubMed  PubMed Central  Google Scholar 

  17. Fatemi G, Gensler LS, Learch TJ, Weisman MH (2014) Spine fractures in ankylosing spondylitis: a case report and review of imaging as well as predisposing factors to falls and fractures. Semin Arthritis Rheum 44(1):20–24

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kim GD, Chae SU, Kim YJ, Choi DH (2013) Osteoporotic lumbar compression fracture in patient with ankylosing spondylitis treated with kyphoplasty. J Bone Metab 20(1):47–50

    Article  PubMed  PubMed Central  Google Scholar 

  19. Laroche M, Lassoued S, Billey T, Bernard J, Mazi B (2007) Male osteoporosis with vertebral fractures? Look for ankylosing spondylitis! A report of 10 cases. J Rheumatol 34(11):2271–2272

    CAS  PubMed  Google Scholar 

  20. Mitra D, Elvins DM, Collins AJ (1999) Biochemical markers of bone metabolism in mild ankylosing spondylitis and their relationship with bone mineral density and vertebral fractures. J Rheumatol 26(10):2201–2204

    CAS  PubMed  Google Scholar 

  21. Mitra D, Elvins DM, Speden DJ, Collins AJ (2000) The prevalence of vertebral fractures in mild ankylosing spondylitis and their relationship to bone mineral density. Rheumatology (Oxford) 39:85–89

    Article  CAS  Google Scholar 

  22. Berlin JA (1997) Does blinding of readers affect the results of meta-analyses? University of Pennsylvania Meta-analysis Blinding Study Group. The Lancet 350(9072):185–186

    Article  CAS  Google Scholar 

  23. DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28:105–114

    Article  PubMed  Google Scholar 

  24. 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(5):1431–1439

    Article  CAS  PubMed  Google Scholar 

  25. Baek HJ, Kang SW, Lee YJ, Shin KC, Lee EB, Yoo CD, Song YW (2005) Osteopenia in men with mild and severe ankylosing spondylitis. Rheumatol Int 26(1):30–34

    Article  CAS  PubMed  Google Scholar 

  26. 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 21:1877–1882

  27. 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(2):117–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ghozlani I, Ghazi M, Nouijai A, Mounach A, Rezqi A, Achemlal L, Bezza A, El Maghraoui A (2009) Prevalence and risk factors of osteoporosis and vertebral fractures in patients with ankylosing spondylitis. Bone 44(5):772–776

    Article  CAS  PubMed  Google Scholar 

  29. Jun JB, Joo KB, Her MY, Kim TH, Bae SC, Yoo DH, Kim SK (2006) Femoral bone mineral density is associated with vertebral fractures in patients with ankylosing spondylitis: a cross-sectional study. J Rheumatol 33(8):1637–1641

    PubMed  Google Scholar 

  30. Kang KY, Kim IJ, Jung SM, Kwok SK, Ju JH, Park KS, Hong YS, Park SH (2014) Incidence and predictors of morphometric vertebral fractures in patients with ankylosing spondylitis. Arthritis Res Ther 16:16 (3:R124)

    Article  Google Scholar 

  31. Klingberg E, Geijer M, Gothlin J, Mellstrom D, Lorentzon M, Hilme E, Hedberg M, Carlsten H, Forsblad-D’Elia H (2012) Vertebral fractures in ankylosing spondylitis are associated with lower bone mineral density in both central and peripheral skeleton. J Rheumatol 39:1987–1995

    Article  PubMed  Google Scholar 

  32. Klingberg E, Lorentzon M, Göthlin J, Mellström D, Geijer M, Ohlsson C, Atkinson EJ, Khosla S, Carlsten H, Forsblad-d’Elia H (2013) Bone microarchitecture in ankylosing spondylitis and the association with bone mineral density, fractures, and syndesmophytes. Arthritis Res Ther 15(6):R179

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lange U, Kluge A, Strunk J, Teichmann J, Bachmann G (2005) Ankylosing spondylitis and bone mineral density-what is the ideal tool for measurement? Rheumatol Int 26:115–120

    Article  PubMed  Google Scholar 

  34. Mermerci Baskan B, Pekin Dogan Y, Sivas F, Bodur H, Ozoran K (2010) The relation between osteoporosis and vitamin D levels and disease activity in ankylosing spondylitis. Rheumatol Int 30:375–378

    Article  CAS  PubMed  Google Scholar 

  35. Prieto-Alhambra D, Muñoz-Ortego J, De Vries F, Vosse D, Arden NK, Bowness P, Cooper C, Diez-Perez A, Vestergaard P (2015) Ankylosing spondylitis confers substantially increased risk of clinical spine fractures: a nationwide case-control study. Osteoporos Int 26(1):85–91

    Article  CAS  PubMed  Google Scholar 

  36. Ulu MA, Batmaz I, Dilek B, Cevik R (2014) Prevalence of osteoporosis and vertebral fractures and related factors in patients with ankylosing spondylitis. Chin Med J (Engl) 127(15):2740–2747

    Google Scholar 

  37. 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(6):1683–1690

    Article  PubMed  Google Scholar 

  38. Kawai VK, Grijalva CG, Arbogast PG, Curtis JR, Solomon DH, Delzell E, Chen L, Ouellet-Hellstrom R, Herrinton L, Liu L, Mitchell EF Jr, Stein CM, Griffin MR (2013) Initiation of tumor necrosis factor α antagonists and risk of fractures in patients with selected rheumatic and autoimmune diseases. Arthritis Care Res (Hoboken) 65(7):1085–1094

    Article  CAS  Google Scholar 

  39. Robinson Y, Sandén B, Olerud C (2013) Increased occurrence of spinal fractures related to ankylosing spondylitis: a prospective 22-year cohort study in 17,764 patients from a national registry in Sweden. Patient Saf Surg 7(1):2

    Article  PubMed  PubMed Central  Google Scholar 

  40. Maas F, Spoorenberg A, Brouwer E, Schilder AM, Chaudhry RN, Wink F, Bootsma H, van der Veer E, Arends S (2016) Radiographic vertebral fractures develop in patients with ankylosing spondylitis during 4 years of TNF-α blocking therapy. Clin Exp Rheumatol 34(2):191–199

  41. Lukasiewicz AM, Bohl DD, Varthi AG, Basques BA, Webb ML, Samuel AM, Grauer JN (2016) Spinal fracture in patients with ankylosing spondylitis: cohort definition, distribution of injuries, and hospital outcomes. Spine (Phila Pa 1976) 41(3):191–196

  42. Maas F, Spoorenberg A, van der Slik BP, van der Veer E, Brouwer E, Bootsma H, Bos R, Wink FR, Arends S (2016) Clinical risk factors for the presence and development of vertebral fractures in patients with ankylosing spondylitis. Arthritis Care Res (Hoboken). doi:10.1002/acr.22980

  43. Geusens P, De Winter L, Quaden D, Vanhoof J, Vosse D, van den Bergh J, Somers V (2015) The prevalence of vertebral fractures in spondyloarthritis: relation to disease characteristics, bone mineral density, syndesmophytes and history of back pain and trauma. Arthritis Res Ther 17:294

  44. Haroon NN, Sriganthan J, Al Ghanim N, Inman RD, Cheung AM (2014) Effect of TNF-alpha inhibitor treatment on bone mineral density in patients with ankylosing spondylitis: a systematic review and meta-analysis. Semin Arthritis Rheum 44(2):155–161

    Article  PubMed  Google Scholar 

  45. Haroon NN, Szabo E, Raboud JM, Mcdonald-Blumer H, Fung L, Josse RG, Inman RD, Cheung AM (2015) Alterations of bone mineral density, bone microarchitecture and strength in patients with ankylosing spondylitis: a cross-sectional study using high-resolution peripheral quantitative computerized tomography and finite element analysis. Arthritis Res Ther 17:377

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nisha Nigil Haroon.

Ethics declarations

Conflict of interest

Nisha Nigil Haroon has received fellowship support from an unrestricted research Grant supported by AMGEN. Cara Pray, Neelufer Irene Feroz and Nisha Nigil Haroon have no conflict of interest.

Human and Animal Rights

This article does not contain any studies with animals performed by any of the authors.

Informed Consent

For this type of study formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pray, C., Feroz, N.I. & Nigil Haroon, N. Bone Mineral Density and Fracture Risk in Ankylosing Spondylitis: A Meta-Analysis. Calcif Tissue Int 101, 182–192 (2017). https://doi.org/10.1007/s00223-017-0274-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-017-0274-3

Keywords

Navigation