Endocrine Abstracts (2013) 32 P72 | DOI: 10.1530/endoabs.32.P72

Circadian rhythm of circulating sclerostin in healthy young men

Santosh H Shankarnarayan1,2, Rupa Ahluwalia2,3, Amanda Hamilton3, Dong L Barraclough2, William D Fraser4 & Jiten P Vora2

1Singleton Hosptial, Swansea, UK; 2University of Liverpool, Liverpool, UK; 3Royal Liverpool and Broadgreen NHS Hospital Trust, Liverpool, UK; 4Norwich Medical School, Norwich, UK.

Introduction: It is recognised that osteocytes, by secreting sclerostin plays a more central role in bone homeostasis. Sclerostin is a physiological inhibitor of bone formation. By binding to the LRP5/6 receptor sclerostin inhibits the Wnt signalling pathway. A cross-sectional study was undertaken to ascertain whether an endogenous sclerostin circadian rhythm exists in healthy individuals.

Subjects and methods: Six healthy young men with normal BMD were admitted overnight. Blood samples were drawn every hour for 24 h samples obtained centrifuged immediately. The serum/plasma was separated and frozen at −70 °C for later analysis. An enzyme linked immunoassay (Biomedica, Austria) was used to measure sclerostin. All samples were assayed in duplicates. The inter and intra assay CV% being 12.3 and <5% respectively.

Statistical analysis: CHRONOLAB 3.0 (Universdade de Vigo, Vigo, Spain) a software package validated for analyzing biological time series by least squares estimation was used to analyze individual and population mean cosinor. The following circadian rhythm parameters were evaluated: 1) midline estimate statistic of rhythm (MESOR), 2) amplitude and 3) acrophase. A p value for the rejection of the zero-amplitude (no rhythm) assumption is determined for each individual and for the group.

Results: A definite sclerostin circadian rhythm was identified in the study population (P=0.028). The mean sclerostin (MESOR) was 84.4±1.4 pmol/l. A nocturnal sclerostin peak (time of onset 0100 h) with concentrations remaining above mean over 4 h was observed. A small but ill sustained increase is noted at 0700 h which culminates in a steep descent to a trough (at 0800 h) the levels remain low throughout the morning till midday (1200 h). The maximum percentage increase in the sclerostin concentration between 0100 h and 0700 h ((value at each time point – 0100 h value)/ 0100 h value × 100)) was 19.7%.

Conclusion: Our results demonstrate a circadian rhythm with a nocturnal peak in the sclerostin secretion for young healthy men.

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