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The Risk Factors of Avascular Necrosis in Patients with Systemic Lupus Erythematosus: a Meta-analysis

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Abstract

The aim of this study was to determine the risk factors for avascular necrosis (AVN) in patients with systemic lupus erythematosus (SLE). Four electronic databases (PubMed, EMBASE, Ovid, and Science Direct) were searched for. The search was performed to identify the articles as to SLE with AVN before September 2013. The clinical and laboratory data were extracted, and a meta-analysis was performed to identify the risk factors for AVN in patients with SLE. Publication bias was assessed with funnel plot and Egger’s test. A total of 995 papers were found from the four databases; 16 studies were finally included. Pooled analysis showed the following result. The result showed that arthritis (odds ratio (OR) = 2.448, 95 % confidence interval (CI) = 1.617–3.707), cushingoid (OR = 3.890, 95 % CI = 1.591–9.510), gastrointestinal involvement (OR = 2.054, 95 % CI = 1.283–3.290), hypertension (OR = 1.482, 95 % CI = 1.093–2.008), oral ulcers (OR = 1.877, 95 % CI = 1.182–2.979), pleuritis (OR = 2.302, 95 % CI = 1.325–4.001), renal disease (OR = 1.475, 95 % CI = 1.124–1.936), and vasculitis (OR = 2.591, 95 % CI = 1.358–4.944) were relevant with AVN in SLE patients. Cytotoxic drug (OR = 1.834, 95 % CI = 1.065–3.156, P = 0.029), the total cumulative dose (Standard Mean Difference (SMD) = 1.104, 95 % CI = 0.118–2.090, P = 0.028), maximum daily dose (SMD = 0.484, 95 % CI = 0.288–0.678, P < 0.001), and mean daily dose (SMD = 1.305, 95 % CI = 0.061–2.549, P = 0.040) were significantly higher in AVN group. There were no significantly laboratory features that appeared in this pooled analysis. We conclude that arthritic, cushingoid, gastrointestinal involvement, hypertension, oral ulcers, pleuritis, renal disease, vasculitis, cytotoxic drug, and steroid treatment may contribute to AVN in SLE patients.

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References

  1. Gutkowski, K., and D. Gutkowska. 2006. Systemic lupus erythematosus (sle). Ginekologia Polska 77: 893–900.

    PubMed  Google Scholar 

  2. Chemaly, R.E., and A.S. Moussalli. 2012. Parkinsonian syndrome as a complication of systemic lupus erythematosus. Report of a case and review of the literature. Journal Medical Libanais. Lebanese Medical Journal 60: 103–105.

    Google Scholar 

  3. Chak, W.K., D.S. Lam, W.H. Lo, C.M. Hui, and S.N. Wong. 2003. Thrombotic thrombocytopenic purpura as a rare complication in childhood systemic lupus erythematosus: case report and literature review. Hong Kong Medical Journal 9: 363–368.

    PubMed  CAS  Google Scholar 

  4. Baizabal Carvallo, J.F., C. Cantú Brito, B. Estañol, and G.S. García Ramos. 2007. Subarachnoid hemorrhage as a complication of systemic lupus erythematosus. Cerebrovascular Diseases 24: 301–304.

    Article  PubMed  CAS  Google Scholar 

  5. Nabibux, M.N., P.A. Dijkmans, and B.A. Dijkmans. 2007. A swinging heart as complication of systemic lupus erythematosus. Clinical Rheumatology 26: 825–826.

    Article  PubMed  Google Scholar 

  6. Mok, M.Y., V.T. Farewell, and D.A. Isenberg. 2000. Risk factors for avascular necrosis of bone in patients with systemic lupus erythematosus: is there a role for antiphospholipid antibodies? Annals of the Rheumatic Diseases 59: 462–467.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Rascu, A., K. Manger, H.G. Kraetsch, J.R. Kalden, and B. Manger. 1996. Osteonecrosis in systemic lupus erythematosus, steroid-induced or a lupus-dependent manifestation? Lupus 5: 323–327.

    Article  PubMed  CAS  Google Scholar 

  8. Dubois, E.L., and L. Cozen. 1960. Avascular(aseptic) bone necrosis associated with systemic lupus erythematosus. JAMA 174: 966–968.

    Article  PubMed  CAS  Google Scholar 

  9. Sayarlioglu, M., N. Yuzbasioglu, M. Inanc, S. Kamali, A. Cefle, O. Karaman, A.M. Onat, R. Avan, G.Y. Cetin, A. Gul, L. Ocal, and O. Aral. 2012. Risk factors for avascular bone necrosis in patients with systemic lupus erythematosus. Rheumatology International 32: 177–182.

    Article  PubMed  CAS  Google Scholar 

  10. Gladman, D.D., M.B. Urowitz, V. Chaudhry-Ahluwalia, D.C. Hallet, and R.J. Cook. 2001. Predictive factors for symptomatic osteonecrosis in patients with systemic lupus erythematosus. Journal of Rheumatology 28: 761–765.

    PubMed  CAS  Google Scholar 

  11. Zizic, T.M., C. Marcoux, D.S. Hungerford, J.V. Dansereau, and M.B. Stevens. 1985. Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus. American Journal of Medicine 79: 596–604.

    Article  PubMed  CAS  Google Scholar 

  12. Kelman, G.J., G.W. Williams, C.W. Colwell Jr., and R.H. Walker. 1990. Steroid-related osteonecrosis of the knee. Two case reports and a literature review. Clinical Orthopaedics and Related Research 257: 171–176.

    PubMed  Google Scholar 

  13. Adleberg, J.S., and G.H. Smith. 1991. Corticosteroid-induced avascular necrosis of the talus. The Journal of Foot Surgery 30: 66–69.

    PubMed  CAS  Google Scholar 

  14. Fialho, S.C., E. Bonfá, L.F. Vitule, E. D’Amico, V. Caparbo, S. Gualandro, and R.M. Pereira. 2007. Disease activity as a major risk factor for osteonecrosis in early systemic lupus erythematosus. Lupus 16: 239–244.

    Article  PubMed  CAS  Google Scholar 

  15. Uea-areewongsa, P., S. Chaiamnuay, P. Narongroeknawin, and P. Asavatanabodee. 2009. Factors associated with osteonecrosis in thai lupus patients: A case control study. Journal of Clinical Rheumatology 15: 345–349.

    Article  PubMed  Google Scholar 

  16. Mok, C.C., C.S. Lau, and R.W. Wong. 1998. Risk factors for avascular bone necrosis in systemic lupus erythematosus. Journal of Rheumatology 37: 895–900.

    Article  CAS  Google Scholar 

  17. Tektonidou, M.G., K. Malagari, P.G. Vlachoyiannopoulos, D.A. Kelekis, and H.M. Moutsopoulos. 2003. Asymptomatic avascular necrosis in patients with primary antiphospholipid syndrome in the absence of corticosteroid use. Arthritis and Rheumatism 48: 732–736.

    Article  PubMed  Google Scholar 

  18. Oinuma, K., Y. Harada, Y. Nawata, K. Takabayashi, I. Abe, K. Kamikawa, and H. Moriya. 2001. Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment. Annals of the Rheumatic Diseases 60: 1145–1148.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Kunyakham, W., C. Foocharoen, A. Mahakkanukrauh, S. Suwannaroj, and R. Nanagara. 2012. Prevalence and risk factor for symptomatic avascular necrosis development in thai systemic lupus erthematosus patients. Asian Pacific Journal of Allergy and Immunology 30: 152–157.

    PubMed  Google Scholar 

  20. Hamijoyo, L., L.J. Llamado, and S.V. Navarra. 2008. Risk factors for avascular necrosis among Filipino patients with systemic lupus erythematosus. International Journal of Rheumatic Diseases 2: 141–147.

    Article  Google Scholar 

  21. Mont, M.A., C.J. Glueck, I.H. Pacheco, P. Wang, D.S. Hungerford, and M. Petri. 1997. Risk factors for osteonecrosis in systemic lupus erythematosus. The Journal of Rheumatology 24: 654–662.

    PubMed  CAS  Google Scholar 

  22. Wang, D.X., G.Y. Li, L. Ma, and G.C. Wang. 2009. A clinical study of femoral head osteonecrosis in patients with systemic lupus erythematosus. Zhonghua Nei Ke Za Zhi 48: 926–929.

    PubMed  Google Scholar 

  23. Abeles, M., J.D. Urman, and N.F. Rothfield. 1978. Aseptic necrosis of bone in systemic lupus erythematousus. Relationship to corticosteroid therapy. Archives of Internal Medicine 138: 750–754.

    Article  PubMed  CAS  Google Scholar 

  24. Usui, M., H. Inoue, S. Yukihiro, and N. Abe. 1997. Nature history of avascular necrosis of the femoral head in systemic lupus erythematosus. Journal of Orthopaedic Science 2: 10–15.

    Article  Google Scholar 

  25. Oh, S.N., W.H. Jee, S.M. Cho, et al. 2004. Osteonecrosis in patients with systemic lupus erythematosus: MR imaging and scintigraphic evaluation. Journal of Clinical Imaging 28: 305–309.

    Article  CAS  Google Scholar 

  26. Asherson, R.A., F. Liote, B. Page, et al. 2014. Avascular necrosis of bone and antiphospholipid antibodies in systemic lupus erythematosus. Journal of Rheumatology 41: 408–410.

    Article  Google Scholar 

  27. Jaovisidha, S., R. Denprechawong, P. Suwannalai, et al. 2007. Asymptomatic avascular osteonecrosis of the hip in new patients diagnosed as systemic lupus erythematosus in ramathibodi hospital. Journal of the Medical Association of Thailand 90: 1382–1390.

    PubMed  Google Scholar 

  28. Aranow, C., S. Zelicof, D. Leslie, et al. 1997. Clinically occult avascular necrosis of the hip in systemic lupus erythematosus. Journal of Rheumatology 24: 2318–2322.

    PubMed  CAS  Google Scholar 

  29. Ono, K., T. Tohjima, and T. Komazawa. 1992. Risk factors of avascular necrosis of the femoral head in patients with systemic lupus erythematosus under high-dose corticosteroid therapy. Clinical. Orthopaedics and Related Research 277: 89–97.

    Google Scholar 

  30. Ghaleb, R.M., G.M. Omar, and M.A. Ibrahim. 2011. Avascular necrosis of bone in systemic lupus erythematosus. The Egyptian Rheumatologist 33: 27–33.

    Article  Google Scholar 

  31. Smith, F.E., D.E. Sweet, C.M. Brunner, and J.S. Davis. 1976. Avascular necrosis in SLE. An apparent predilection for young patients. Annals of the Rheumatic Diseases 35: 227–232.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Calvo-Alén, J., G. McGwin, S. Toloza, M. Fernández, J.M. Roseman, H.M. Bastian, E.J. Cepeda, E.B. González, B.A. Baethge, B.J. Fessler, L.M. Vilá, J.D. Reveille, G.S. Alarcón, and for the LUMINA Study Group. 2006. Systemic lupus erthematosus in a multiethnic US cohort (LUMINA): XXIV. Cytotoxic treatment is an additional risk factor for the development of symptomatic osteonecrosis in lupus patients:results of a nested matched case–control study. Annals of the Rheumatic Diseases 65: 785–790.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Watanabe, T., T. Tsuchida, N. Kanda, and K. Tamaki. 1997. Avascular necrosis of bone in systemic lupus erythematosus. The predictive role of precipitating autoantibodies. Scandinavian Journal of Rheumatology 26: 184–187.

    Article  PubMed  CAS  Google Scholar 

  34. Massardo, L., S. Jacobelli, M. Leissner, M. González, L. Villarroel, and S. Rivero. 1992. High-dose intravenous methylprednisolone therapy associated with osteonecrosis in patients with systemic lupus erythematosus. Lupus 1: 401–405.

    Article  PubMed  CAS  Google Scholar 

  35. Prasad, R., D. Ibanez, D. Gladman, and M. Urowitz. 2007. The role of non-corticosteroid related factors in osteonecrosis (ON) in systemic lupus erythematosus: a nested case–control study of inception patients. Lupus 16: 157–162.

    PubMed  CAS  Google Scholar 

  36. Nagasawa, K., Y. Ishii, T. Mayumi, Y. Tada, A. Ueda, Y. Yamauchi, T. Kusaba, and Y. Niho. 1989. Avascular necrosis of bone in systemic lupus erythematosus: possible role of haemostatic abnormalities. Annals of the Rheumatic Diseases 48: 672–676.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Aptekar, R.G., J.H. Klippel, K.E. Becker, D.A. Carson, W.E. Seaman, and J.L. Decker. 1974. Avascular Necrosis of the talus, scaphoid, and metatarsal head in systemic lupus erythematosus. Clinical Orthopaedics and Related Research 101: 127–128.

    PubMed  Google Scholar 

  38. Crew, R.J., J. Radhakrishnan, and G. Appel. 2004. Complication of the nephritic syndrome and their treatment. Clinical Nephrology 62: 245–259.

    Article  PubMed  CAS  Google Scholar 

  39. Mok, C.C., K.H. Tong, C.H. To, Y.P. Siu, L.Y. Ho, and T.C. Au. 2007. Risk and predictors of arterial thrombosis in lupus and non-lupus primary glomerulonephritis: a comparative study. Medicine (Baltimore) 86: 203–209.

    Article  Google Scholar 

  40. Parag, K.B., S.R. Somers, Y.K. Seedat, S. Byrne, C.M. Da Cruz, and G. Kenoyer. 1990. Arterial thrombosis in nephritic syndrome. American Journal of Kidney Diseases 15: 176–177.

    Article  PubMed  CAS  Google Scholar 

  41. Kim, H.J., C.H. Park, C.M. Kang, H.C. Park, C.Y. Kim, and Y.S. Cho. 1993. Arterial thrombosis associated with nephritic syndrome-a case report and review (adult cases in the English literature). Journal of Korean Medical Science 8: 230–234.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Epidemiology and Statistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, People’s Republic of China

    Kao-Kao Zhu, Wang-Dong Xu, Hai-Feng Pan, Min Zhang, Jing Ni & Dong-Qing Ye

  2. Anhui Academy of Medical Sciences, 15 Yonghong Road, Hefei, 230032, Anhui, People’s Republic of China

    Fu-Yang Ge

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Zhu, KK., Xu, WD., Pan, HF. et al. The Risk Factors of Avascular Necrosis in Patients with Systemic Lupus Erythematosus: a Meta-analysis. Inflammation 37, 1852–1864 (2014). https://doi.org/10.1007/s10753-014-9917-y

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