Circulating levels of receptor activator of nuclear factor-kappaB ligand/osteoprotegerin/macrophage-colony stimulating factor in a presumably healthy human population.
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.
Trofimov
Svetlana
S
Sackler Faculty of Medicine, Tel Aviv University, Israel.
Pantsulaia
I
I
Pantsulaia
Ia
Ia
Kobyliansky
Eugene
E
Livshits
Gregory
G
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
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