title: 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.
abstract: 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.
authors.affiliation: Department of Medicine, School of Medicine, The University of Alabama at Birmingham, USA.
authors.forename: J
authors.initials: J
authors.lastname: Calvo-Alén
authors.forename: G
authors.initials: G
authors.lastname: McGwin
authors.forename: S
authors.initials: S
authors.lastname: Toloza
authors.forename: M
authors.initials: M
authors.lastname: Fernández
authors.forename: J M
authors.initials: JM
authors.lastname: Roseman
authors.forename: H M
authors.initials: HM
authors.lastname: Bastian
authors.forename: E J
authors.initials: EJ
authors.lastname: Cepeda
authors.forename: E B
authors.initials: EB
authors.lastname: González
authors.forename: B A
authors.initials: BA
authors.lastname: Baethge
authors.forename: B J
authors.initials: BJ
authors.lastname: Fessler
authors.forename: L M
authors.initials: LM
authors.lastname: Vilá
authors.forename: J D
authors.initials: JD
authors.lastname: Reveille
authors.forename: G S
authors.initials: GS
authors.lastname: Alarcón
mesh_terms: D000328:Adult; D001741:Black or African American; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005006:Ethnicity; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006630:Hispanic or Latino; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy / Q000208:ethnology*; D008297:Male; D010020:Osteonecrosis / Q000209:etiology*; D014481:United States; D044465:White People
chemical_list: D000903:Antibiotics, Antineoplastic; D005938:Glucocorticoids; D006886:Hydroxychloroquine