title: RANKL:osteoprotegerin ratio and bone mineral density in children with untreated juvenile dermatomyositis.
abstract: OBJECTIVE
  To determine bone mineral density (BMD) in patients at the time of diagnosis of juvenile dermatomyositis (DM), to compare the RANKL:osteoprotegerin (OPG) ratio in patients with juvenile DM with that in healthy control subjects, and to evaluate whether BMD is associated with the RANKL:OPG ratio and the duration of untreated disease.
  
  
  METHODS
  Thirty-seven children with juvenile DM were enrolled. Dual x-ray absorptiometry (DXA) was performed before treatment, and Z scores for the lumbar spine (L1-L4) were determined. The duration of untreated disease was defined as the period of time from the onset of rash or weakness to the time at which DXA was performed. Serum specimens obtained at the time of DXA were analyzed for concentrations of RANKL and OPG, using enzyme-linked immunosorbent assay. The RANKL:OPG ratio was also determined in 44 age-matched healthy control subjects.
  
  
  RESULTS
  At the time of diagnosis of juvenile DM, patients had a significantly increased RANKL:OPG ratio compared with that in healthy children (mean +/- SD 2.19 +/- 3.03 and 0.13 +/- 0.17, respectively; P < 0.0001). In patients with a lumbar spine BMD Z score of -1.5 or lower, the RANKL:OPG ratio was significantly higher than that in patients with a lumbar spine BMD Z score higher than -1.5 (P = 0.038). Lumbar spine BMD Z scores (mean +/- SD -0.13 +/- 1.19 [range -2.10 to 2.85]) were inversely associated with the duration of untreated disease (R = -0.50, P = 0.003).
  
  
  CONCLUSIONS
  Children with juvenile DM have an elevated RANKL:OPG ratio at the time of diagnosis, resulting in expansion of the number of osteoclasts and activation of the bone resorptive function. This may lead to a lack of normal bone mineral accretion and a subsequent reduction in the lumbar spine BMD Z score. Patients with a longer duration of untreated juvenile DM have reduced lumbar spine BMD Z scores. These data suggest that early diagnosis could reduce the likelihood of reduced lumbar spine BMD in these patients by prompting intervention strategies at an early stage.
authors.affiliation: Children's Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60614, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Rouster-Stevens
authors.forename: Craig B
authors.initials: CB
authors.lastname: Langman
authors.forename: Heather E
authors.initials: HE
authors.lastname: Price
authors.forename: Roopa
authors.initials: R
authors.lastname: Seshadri
authors.forename: Richard M
authors.initials: RM
authors.lastname: Shore
authors.forename: Kathy
authors.initials: K
authors.lastname: Abbott
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Pachman
mesh_terms: D015502:Absorptiometry, Photon; D015519:Bone Density / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000097:blood* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010010:Osteoclasts / Q000473:pathology; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human