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Objectives: To determine the ranges of variation of circulating receptor activator of nuclear factor-kB 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. Subjects and 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 ¼ 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 ¼ 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 ¼ 0.29, P , 0.001) compared with men (r ¼ 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 ¼ 2 0.39, P , 0.01; r ¼ 20.25, P , 0.001 respectively). sRANKL did not correlate with either age or sex hormones in either women or men. Conclusion: 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.European Journal of Endocrinology 150 305-311

OBJECTIVE: To ascertain the extent to which relationships between obesity (OB) and blood pressure (BP) can be explained by an individual's leptin plasma levels. DESIGN: Pedigree-based cross-sectional study in an apparently healthy population of European origin. SUBJECTS: The study sample is comprised of 90 nuclear and more complex families totaling 210 male and 213 female subjects aged 18-75 y, randomly recruited in Bashkorstan Autonomic region, Russia. MEASUREMENTS: Various fatness and fat distribution traits (including nine circumferences (CRCs), and eight skinfolds (CKFs) by anthropometry), blood pressure, and plasma leptin levels (by ELISA kits). RESULTS: Adjustment for circulating leptin led to attenuation of the magnitude of correlations between OB and BP, regardless of trait pair and sex cohort. Some of these correlations became statistically nonsignificant. All familial effects were gone, and heritability estimates became virtually zero after adjustment of each of the OB traits and systolic blood pressure (SBP) in offspring for leptin values in parents. CONCLUSION: BP and OB covariation is substantially mediated by circulating leptin levels. As a result, body fat has only a weak independent effect on BP variation after adjustment for leptin levels. Our findings also strongly suggest that genetic variation in body mass index, SKFs, and even body CRCs, as well as of SBP is due to genetic variation of leptin. Genetic variation of diastolic blood pressure in the present sample, however, shared very little with that of leptin.