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Dickkopf-1 and Sclerostin Serum Levels in Patients with Systemic Mastocytosis

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Abstract

Bone involvement, mainly osteoporosis but also osteosclerosis, is frequent in patients with indolent systemic mastocytosis (ISM). The recent characterization of the canonical Wnt/β-catenin pathway in the regulation of bone remodeling provided important insights for our understanding of the pathophysiology of a number of conditions. The regulation of Wnt pathway in bone is predominantly driven by the production of receptor inhibitors such as Dickkopf-1 (DKK1) and sclerostin (SOST). This study aimed to explore if the various bone involvements in patients with ISM might be explained by variations in serum levels of DKK1 and SOST. This is a cross-sectional study in an adult ISM cohort (13 men and 13 women with diagnosed ISM) and fifty-two healthy sex and age-matched controls. Early morning, fasting and venous sampling was obtained in all subjects. The main outcome measures were serum bone-specific alkaline phosphatase (bALP), C-terminal telopeptides of type I collagene (CTX), DKK1, SOST, parathyroid hormone (PTH), bone mineral density, and prevalent vertebral fractures. Mean DKK1 serum levels were about two-folds higher in patients, than in controls (65,0 ± 43.3 vs. 33.1 ± 19.4 pmol/L, respectively; p < 0.001), irrespective of the presence of osteoporotic or diffuse osteosclerotic bone involvement. DKK1 serum levels were positively correlated with PTH and both CTX and bALP. Mean SOST serum levels were not significantly different in patients versus controls, and we did not observe any significant correlation between SOST and any available clinical or laboratory parameters, with the only exception of a positive correlation with age. In conclusion, in our study, we observed that DKK1, but not SOST, serum levels significantly increased in ISM patients with various bone involvements, and correlated with PTH and bone turnover markers. Our results suggest that the Wnt/β-catenin pathway is not primarily involved in the pathophysiology of the array of bone involvement in ISM.

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Acknowledgments

We thank Caterina Fraccarollo for excellent technical assistance. The authors thank Sara Rossini and Vidya Kunnathully who provided editorial assistance.

Conflict of Interest

Maurizio Rossini, Ombretta Viapiana, Roberta Zanotti, Gaia Tripi, Omar Perbellini, Luca Idolazzi, Massimiliano Bonifacio, Silvano Adami, and Davide Gatti have no conflict of interest.

Human and Animal Rights and Informed Consent

The study was approved by the local institutional review board. It was conducted in accordance with the ethics principles of the Declaration of Helsinki and was approved by the local ethics committee. Informed consent was obtained from all patients and control subjects.

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Authors and Affiliations

  1. Rheumatology Section, Department of Medicine, University of Verona, Policlinico Borgo Roma, Piazzale Scuro, 10, 37134, Verona, Italy

    Maurizio Rossini, Ombretta Viapiana, Gaia Tripi, Luca Idolazzi, Silvano Adami & Davide Gatti

  2. Hematology Section, Department of Medicine, University of Verona, Verona, Italy

    Roberta Zanotti, Omar Perbellini & Massimiliano Bonifacio

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  1. Maurizio Rossini
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Correspondence to Maurizio Rossini.

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Rossini, M., Viapiana, O., Zanotti, R. et al. Dickkopf-1 and Sclerostin Serum Levels in Patients with Systemic Mastocytosis. Calcif Tissue Int 96, 410–416 (2015). https://doi.org/10.1007/s00223-015-9969-5

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  • DOI: https://doi.org/10.1007/s00223-015-9969-5

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