title: Changes in macrophage inhibitory factor correlate with changes in bone mineral density in glucocorticoid-treated patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To investigate whether changes in bone density and turnover are associated with changes in inflammatory mediators in RA patients treated with glucocorticoids (GCs) upon vitamin D treatment in comparison with alendronate treatment.
  
  
  METHODS
  RA patients (n = 40) on long-term oral GC treatment received either alfacalcidol or alendronate. At baseline and after 18 months, we measured cytokines capable of antagonizing GCs [macrophage migration inhibitory factor (MIF), IL-13 and IL-7], cytokines causing T-cell differentiation (IL-6, IL-7, IL-12, IL-10 and IL-23) and cytokines produced by effector T cells (IFN-γ, IL-4, IL-17, IL-22). Associations of cytokine profiles with bone markers and BMD changes of the lumbar spine were explored using multiple regression analyses that corrected for study medication and risk factors of osteoporosis (gender, age, cumulative/change in GC dose).
  
  
  RESULTS
  Alendronate, unlike alfacalcidol, increased BMD changes in the lumbar spine. Most cytokines were below detection limits. MIF and IL-23 were detectable in almost all samples; neither alfacalcidol nor alendronate significantly influenced serum concentrations of these cytokines. Interestingly, changes in MIF correlated positively with changes in BMD of the lumber spine (Pearson's correlation = 0.31), and in multivariate analysis adjusting for treatment, age and change in GC dose (P = 0.022).
  
  
  CONCLUSIONS
  During GC treatment, changes in the GC-antagonist MIF were positively correlated with changes in BMD, which could mean MIF has bone-protecting capacities in patients suffering from GC-induced bone destruction. Further studies need to validate the importance of these findings.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, F02.127, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. mail@hoesjn.org
authors.forename: Jos N
authors.initials: JN
authors.lastname: Hoes
authors.forename: Marlies C
authors.initials: MC
authors.lastname: Van der Goes
authors.forename: Johannes W G
authors.initials: JW
authors.lastname: Jacobs
authors.forename: Floris P G J
authors.initials: FP
authors.lastname: Lafeber
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: Joel A G
authors.initials: JA
authors.lastname: Van Roon
mesh_terms: D019386:Alendronate / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D006887:Hydroxycholecalciferols / Q000627:therapeutic use; D053759:Interleukin-23 / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D011859:Radiography
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; D006887:Hydroxycholecalciferols; D053759:Interleukin-23; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; C008088:alfacalcidol; D019386:Alendronate