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Systemic lupus erythematosus 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
  1. J Calvo-Alén1,
  2. G McGwin2,
  3. S Toloza1,
  4. M Fernández1,
  5. J M Roseman3,
  6. H M Bastian1,
  7. E J Cepeda4,
  8. E B González5,
  9. B A Baethge5,
  10. B J Fessler1,
  11. L M Vilá6,
  12. J D Reveille4,
  13. G S Alarcón1,
  14. for the LUMINA Study Group
  1. 1Department of Medicine (Division of Clinical Immunology and Rheumatology), School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA; and the Department of Medicine (Division of Clinical Immunology and Rheumatology)
  2. 2Department of Surgery (Section of Trauma, Burns, and Critical Care), School of Medicine, The University of Alabama at Birmingham
  3. 3Department of Epidemiology, School of Public Health, The University of Alabama at Birmingham
  4. 4The University of Texas Health Science Center at Houston (Division of Rheumatology), Houston, Texas, USA
  5. 5The University of Texas Medical Branch at Galveston (Division of Rheumatology), Galveston, Texas
  6. 6The University of Puerto Rico Medical Sciences Campus, Department of Internal Medicine (Division of Rheumatology), San Juan, Puerto Rico
  1. Correspondence to:
    Dr Graciela S Alarcón
    830 Faculty Office Tower, 510 20th Street South, Birmingham, Alabama 35294-3408, USA; graciela.alarcon{at}


Background: Osteonecrosis is common in systemic lupus erythematosus (SLE) and often disabling. The role of glucocorticoids in its development is well known.

Objective: To explore other possible risk factors for osteonecrosis in SLE.

Methods: A nested matched case–control study undertaken in the context of a large, longitudinal, multiethnic lupus cohort (LUMINA), currently formed of 571 SLE patients meeting American College of Rheumatology criteria. All those developing symptomatic osteonecrosis after the diagnosis of SLE were considered cases. Two controls matched for age, disease duration, ethnicity, and centre were selected for each case. Cases and controls were compared by univariable analyses using selected variables. Variables with p<0.10 and those thought clinically relevant were entered into conditional logistic regression models including either the average dose or the highest dose of glucocorticoids, with osteonecrosis as the dependent variable.

Results: 32 cases were identified and 59 matched controls selected (in five cases only one control could be found). By univariable analyses, both groups were largely comparable for socioeconomic-demographic, clinical, and laboratory variables. Cases were less exposed to hydroxychloroquine (as assessed by the percentage of exposure time) (p = 0.026), used higher doses of glucocorticoids (average and highest doses) (p = 0.011 and 0.001, respectively), and received cytotoxic drugs more often (p = 0.015). In the multivariable analyses only cytotoxic drug use (both models) and the highest dose of glucocorticoids remained associated with the occurrence of osteonecrosis.

Conclusions: Cytotoxic drug use is a risk factor for the development of symptomatic osteonecrosis in SLE patients, along with glucocorticoids. No definite protective factors were identified.

  • ACR, American College of Rheumatology
  • aPL, anti-phospholipid antibodies
  • LAC, lupus anticoagulant
  • LUMINA, Lupus in Minorities: Nature v Nurture
  • NSAID, non-steroidal anti-inflammatory drug
  • SDI, Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index
  • SLE, systemic lupus erythematosus
  • systemic lupus erythematosus
  • osteonecrosis
  • glucocorticoids
  • cytotoxic treatment

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