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Acute decline in serum sclerostin in response to PTH infusion in healthy men.

ABSTRACT: Animal models suggest that the osteoblast-stimulating actions of PTH are mediated by acute suppression of sclerostin, an inhibitor of the anabolic Wnt pathway. The immediate physiological changes in serum sclerostin in response to PTH infusion have not been reported in human studies.We sought to determine the acute physiological effects of PTH infusion on serum sclerostin and bone turnover markers in healthy adult men.Fifty-three healthy adult men underwent an 18-h iv infusion of human PTH(1-34) at a dose of 0.55 U/kg · h.Serum levels of ionized calcium, sclerostin, and markers of bone formation (osteocalcin and amino-terminal propeptide of type I procollagen) and bone resorption (C-telopeptide and N-telopeptide) were obtained at 0, 6, 12, and 18 h.Serum ionized calcium, C-telopeptide, and N-telopeptide increased, and osteocalcin and amino-terminal propeptide of type I procollagen fell linearly throughout the PTH infusion (P < 0.001 for all). Average ± sem sclerostin levels declined from 936 ± 65 to 813 ± 63 pg/ml at 6 h (P < 0.001) and remained stably suppressed for the duration of the PTH infusion. There were no significant correlations between change in sclerostin and change in bone markers.Serum sclerostin declined in response to acute PTH infusion within 6 h in healthy adult men. The early plateau in sclerostin suppression may indicate that maximal stimulation of the Wnt pathway is achieved quickly after exposure to PTH. Our findings support the hypothesis that PTH may mediate its anabolic effects in part via suppression of sclerostin.

SUBMITTER: Yu EW

PROVIDER: S-EPMC3205893 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Acute decline in serum sclerostin in response to PTH infusion in healthy men.

Yu Elaine W EW Kumbhani Ruchit R Siwila-Sackman Erica E Leder Benjamin Z BZ

The Journal of clinical endocrinology and metabolism 20110824 11

<h4>Context</h4>Animal models suggest that the osteoblast-stimulating actions of PTH are mediated by acute suppression of sclerostin, an inhibitor of the anabolic Wnt pathway. The immediate physiological changes in serum sclerostin in response to PTH infusion have not been reported in human studies.<h4>Objective</h4>We sought to determine the acute physiological effects of PTH infusion on serum sclerostin and bone turnover markers in healthy adult men.<h4>Design, setting, and participants</h4>Fi ...[more]

PMID: 21865370

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Project description:BackgroundFermentation is a widely used method of natural food preservation that has consequences on the nutritional value of the transformed food. Fermented dairy products are increasingly investigated in view of their ability to exert health benefits beyond their nutritional qualities.ObjectiveTo explore the mechanisms underpinning the health benefits of fermented dairy intake, the present study followed the effects of milk fermentation, from changes in the product metabolome to consequences on the human serum metabolome after its ingestion.MethodsA randomized crossover study design was conducted in 14 healthy men [mean age: 24.6 y; mean body mass index (in kg/m2): 21.8]. At the beginning of each test phase, serum samples were taken 6 h postprandially after the ingestion of 800 g of a nonfermented milk or a probiotic yogurt. During the 2-wk test phases, subjects consumed 400 g of the assigned test product daily (200 g, 2 times/d). Serum samples were taken from fasting participants at the end of each test phase. The serum metabolome was assessed through the use of LC-MS-based untargeted metabolomics.ResultsPostprandial serum metabolomes after milk or yogurt intake could be differentiated [orthogonal projections to latent structures discriminant analysis (OPLS-DA) Q2 = 0.74]. Yogurt intake was characterized by higher concentrations of 7 free amino acids (including proline, P = 0.03), reduced concentrations of 5 bile acids (including glycocholic acid, P = 0.04), and modulation of 4 indole derivative compounds (including indole lactic acid, P = 0.01). Fasting serum samples after 2 wk of daily intake of milk or yogurt could also be differentiated based on their metabolic profiles (OPLS-DA Q2 = 0.56) and were discussed in light of the postprandial results.ConclusionMetabolic pathways related to amino acids, indole derivatives, and bile acids were modulated in healthy men by the intake of yogurt. Further investigation to explore novel health effects of fermented dairy products is warranted.This trial was registered at clinicaltrials.gov as NCT02230345.

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Acute decline in serum sclerostin in response to PTH infusion in healthy men.

Publications

Acute decline in serum sclerostin in response to PTH infusion in healthy men.

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