title: Circulating levels of receptor activator of nuclear factor-kappaB ligand/osteoprotegerin/macrophage-colony stimulating factor in a presumably healthy human population.
abstract: OBJECTIVE
  To determine the ranges of variation of circulating receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG)/macrophage-colony stimulating factor(M-CSF) and to ascertain their potential relationships with age, sex and menopausal status in women, and with sex hormones in a population-based healthy cohort.
  
  
  METHODS
  Blood samples were collected with EDTA after an overnight fast. The plasma levels of each of the above biochemical indices were measured by ELISA in a total of 566 apparently healthy individuals aged 18-75 years.
  
  
  RESULTS
  The plasma concentrations of cytokine molecules in the entire sample ranged from 674 to 4929 pg/ml for OPG, from 105 to 4468 pg/ml for soluble RANKL (sRANKL), and from 187 to 7604 pg/ml for M-CSF. The OPG levels demonstrated a clear positive correlation with age in both sexes (r=0.42 and 0.43, P<0.001, for men and women respectively). Application of the two-interval mathematical model revealed that in females OPG levels were age-independent until age 42, but then showed clear and significant correlation with age (r=0.48, P<0.001). As a result, young females (before 42 years) had a substantially lower average OPG level, 1377.8+/-327.68 pg/ml, in comparison with older women, 1666.02+/-397.14 pg/ml. The M-CSF correlation with age was significantly greater in women (r=0.29, P<0.001) compared with men (r=0.17, P<0.01). Significant negative correlations between plasma levels of both OPG and M-CSF with estradiol concentrations were observed in women (r=-0.39, P<0.01; r=-0.25, P<0.001 respectively). sRANKL did not correlate with either age or sex hormones in either women or men.
  
  
  CONCLUSIONS
  Age and sex affect differently the interindividual variation of OPG, RANKL and M-CSF. Our observations could form the basis for further research to establish provisional reference limits for OPG and RANKL, which are potential markers for benign and malignant processes in bone.
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Trofimov
authors.forename: I
authors.initials: I
authors.lastname: Pantsulaia
authors.forename: Ia
authors.initials: Ia
authors.lastname: Pantsulaia
authors.forename: Eugene
authors.initials: E
authors.lastname: Kobyliansky
authors.forename: Gregory
authors.initials: G
authors.lastname: Livshits
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015519:Bone Density / Q000502:physiology; D002352:Carrier Proteins / Q000097:blood*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D053245:RANK Ligand; D011863:Radioimmunoassay; D053246:Receptor Activator of Nuclear Factor-kappa B; D012737:Sex Factors; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D013739:Testosterone; D004958:Estradiol; D016173:Macrophage Colony-Stimulating Factor