nach oben

Erschienen in:

01.05.2015 | Original Research

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

verfasst von: Maurizio Rossini, Ombretta Viapiana, Roberta Zanotti, Gaia Tripi, Omar Perbellini, Luca Idolazzi, Massimiliano Bonifacio, Silvano Adami, Davide Gatti

Erschienen in: Calcified Tissue International | Ausgabe 5/2015

Einloggen, um Zugang zu erhalten

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.

Horny HP, Metcalfe DD, Bennett JM et al (2008) Mastocytosis. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO classification of tumors of hematopoietic and lymphoid tissues, 4th edn. International Agency for Research and Cancer (IARC), Lyon, pp 54–63

Escribano L, Alvarez-Twose I, Sanchez-Munoz L, Garcia-Montero A, Nunez R, Almeida J, Jara-Acevedo M, Teodósio C, García-Cosío M, Bellas C, Orfao A (2009) Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish network on mastocytosis in a series of 145 patients. J Allergy Clin Immunol 124:514–521CrossRefPubMed

Rossini M, Zanotti R, Viapiana O et al (2014) Bone involvement and osteoporosis in mastocytosis. Immunol Allergy Clin North Am 34:383–396CrossRefPubMed

Theoharides TC, Alysandratos KD, Angelidou A, Delivanis DA, Sismanopoulos N, Zhang B, Asadi S, Vasiadi M, Weng Z, Miniati A, Kalogeromitros D (2012) Mast cells and inflammation. Biochim Biophys Acta 1822:21–33CrossRefPubMedCentralPubMed

Guillaume N, Desoutter J, Chandesris O, Merlusca L, Henry I, Georgin-Lavialle S, Barete S, Hirsch I, Bouredji D, Royer B, Gruson B, Lok C, Sevestre H, Mentaverri R, Brazier M, Meynier J, Hermine O, Marolleau JP, Kamel S, Damaj G (2013) Bone complications of mastocytosis: a link between clinical and biological characteristics. Am J Med 126(75):e1–e7PubMed

Rabenhorst A, Christopeit B, Leja S, Gerbaulet A, Kleiner S, Forster A, Raap U, Wickenauser C, Hartmann K (2013) Serum levels of bone cytokines are increased in indolent systemic mastocytosis associated with osteopenia or osteoporosis. J Allergy Clin Immunol 132:1234–1237CrossRefPubMed

Rossini M, Adami S, Zanotti R, Viapiana O, Idolazzi L, Biondan M, Gatti D (2014) Serum levels of bone cytokines in indolent systemic mastocytosis associated with osteopenia or osteoporosis. J Allergy Clin Immunol 133:933–935CrossRefPubMed

Rossini M, Zanotti R, Bonadonna P, Artuso A, Caruso B, Schena D, Vecchiato D, Bonifacio M, Viapiana O, Gatti D, Senna G, Riccio A, Passalacqua G, Pizzolo G, Adami S (2011) Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49:880–885CrossRefPubMed

Baron R, Rawadi G (2007) Minireview: targeting the Wnt/β-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 148:2635–2643CrossRefPubMed

10.

Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280:19883–19887CrossRefPubMed

11.

Bafico A, Liu G, Yaniv A, Gazit A, Aaronson S (2001) Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol 3:683–686CrossRefPubMed

12.

Atkins GJ, Rowe PS, Lim HP, Welldon KJ, Ormsby R, Wijenayaka AR, Zelenchuk L, Evdokiou A, Findlay DM (2011) Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism. J Bone Miner Res 26:1425–1436CrossRefPubMedCentralPubMed

13.

Moester MJ, Papapoulos SE, LöwikCW, van Bezooijen RL (2010) Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 87:99–107CrossRefPubMedCentralPubMed

14.

Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577–589CrossRefPubMedCentralPubMed

15.

van Lierop AH, Hamdy NA, van Egmond ME, Bakker E, Dikkers FG, Papapoulos SE (2013) Van Buchem disease: clinical, biochemical, and densitometric features of patients and disease carriers. J Bone Miner Res 28:848–854CrossRefPubMed

16.

Li J, Sarosi I, Cattley RC, Pretorius J, Asuncion F, Grisanti M, Morony S, Adamu S, Geng Z, Qiu W, Kostenuik P, Lacey DL, Simonet WS, Bolon B, Qian X, Shalhoub V, Ominsky MS, Zhu KH, Li X, Richards WG (2006) Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 39:754–766CrossRefPubMed

17.

Morvan F, Boulukos K, Cle´ment-Lacroix P, Roman SR, Suc-Royer I, Vayssie`re B, Ammann P, Martin P, Pinho S, Pognonec P, Mollat P, Niehrs C, Baron R, Rawadi G (2006) Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 21:934–945CrossRefPubMed

18.

Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494CrossRefPubMed

19.

Bonadonna P, Perbellini O, Passalacqua G, Caruso B, Colarossi S, Dal Fior D, Castellani L, Bonetto C, Frattini F, Dama A, Martinelli G, Chilosi M, Senna G, Pizzolo G, Zanotti R (2009) Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol 123:680–686CrossRefPubMed

20.

Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO study group. Osteoporos Int 4:368–381CrossRefPubMed

21.

Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148CrossRefPubMed

22.

Politou MC, Heath DJ, Rahemtulla A, Szydlo R, Anagnostopoulos A, Dimopoulos MA, Croucher PI, Terpos E (2006) Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. Int J Cancer 119:1728–1731CrossRefPubMed

23.

Terpos E, Christoulas D, Katodritou E, Bratengeier C, Gkotzamanidou M, Michalis E, Delimpasi S, Pouli A, Meletis J, Kastritis E, Zervas K, Dimopoulos MA (2012) Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: reduction post-bortezomib monotherapy. Int J Cancer 131:1466–1471CrossRefPubMed

24.

Atkins GJ, Kostakis P, Pan B, Farrugia A, Gronthos S, Evdokiou A, Harrison K, Findlay DM, Zannettino AC (2003) RANKL expression is related to the differentiation state of human osteoblasts. J Bone Miner Res 18:1088–1098CrossRefPubMed

25.

van Lierop AH, Moester MJ, Hamdy NA, Papapoulos SE (2014) Serum Dickkopf 1 levels in sclerostin deficiency. J Clin Endocrinol Metab 99:E252–E256CrossRefPubMed

26.

Rossini M, Viapiana O, Adami S, Idolazzi L, Zanotti R, Gatti D (2015) Rapid skeletal turnover in radiographic mimic of osteopetrosis might be secondary to systemic mastocytosis. J Bone Miner Res (in press)

27.

Seitz S, Barvencik F, Koehne T, Priemel M, Pogoda P, Semler J, Minne H, Pfeiffer M, Zustin J, Püschel K, Eulenburg C, Schinke T, Amling M (2013) Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis. Osteoporos Int 24:2325–2334CrossRefPubMed

28.

Rossini M, Zanotti R, Viapiana O, Tripi G, Idolazzi L, Biondan M, Orsolini G, Bonadonna P, Adami S, Gatti D (2014) Zoledronic acid in osteoporosis secondary to mastocytosis. Am J Med 127(1127):e1–e4PubMed

29.

Viapiana O, Fracassi E, Troplini S, Idolazzi L, Rossini M, Adami S, Gatti D (2013) Sclerostin and DKK1 in primary hyperparathyroidism. Calcif Tissue Int 92:324–329CrossRefPubMed

30.

Gatti D, Viapiana O, Idolazzi L, Fracassi E, Rossini M, Adami S (2011) The waning of teriparatide effect on bone formation markers in postmenopausal osteoporosis is associated with increasing serum levels of DKK1. J Clin Endocrinol Metab 96:1555–1559CrossRefPubMed

31.

Rossini M, Gatti D, Adami S (2013) Involvement of WNT/b-catenin signaling in the treatment of osteoporosis. Calcif Tissue Int 93:121–132CrossRefPubMed

32.

Mirza FS, Padhi ID, Raisz LG, Lorenzo JA (2010) Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 95:1991–1997CrossRefPubMedCentralPubMed

33.

Ardawi MS, Al-Kadi HA, Rouzi AA, Qari MH (2011) Determinants of serum sclerostin in healthy pre- and postmenopausal women. J Bone Mineral Res 26:2812–2822CrossRef

34.

Amrein K, Amrein S, Drexler C, Dimai HP, Dobnig H, Pfeifer K, Tomaschitz A, Pieber TR, Fahrleitner-Pammer A (2012) Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults. J Clin Endocrinol Metab 97:148–154CrossRefPubMed

Titel: Dickkopf-1 and Sclerostin Serum Levels in Patients with Systemic Mastocytosis
verfasst von: Maurizio Rossini
Ombretta Viapiana
Roberta Zanotti
Gaia Tripi
Omar Perbellini
Luca Idolazzi
Massimiliano Bonifacio
Silvano Adami
Davide Gatti
Publikationsdatum: 01.05.2015
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 5/2015
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-015-9969-5

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

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

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Costims – das nächste heiße Ding in der Krebstherapie?

Perioperative Checkpointhemmer-Therapie verbessert NSCLC-Prognose

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

GLP-1-Agonisten können Fortschreiten diabetischer Retinopathie begünstigen

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2015

A Pediatric Bone Mass Scan has Poor Ability to Predict Peak Bone Mass: An 11-Year Prospective Study in 121 Children

Parathyroid Hormone, Calcium, and Sodium Bridging Between Osteoporosis and Hypertension in Postmenopausal Korean Women

A Mutation in CTSK Gene in an Autosomal Recessive Pycnodysostosis Family of Chinese Origin

Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial

Deteriorating Effect on Bone Metabolism and Microstructure by Passive Cigarette Smoking Through Dual Actions on Osteoblast and Osteoclast

Development of a Cyclosporin-A-Induced Immune Tolerant Rat Model to Test Marrow Allograft Cell Type Effects on Bone Repair

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Costims – das nächste heiße Ding in der Krebstherapie?

Perioperative Checkpointhemmer-Therapie verbessert NSCLC-Prognose

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

GLP-1-Agonisten können Fortschreiten diabetischer Retinopathie begünstigen

Update Innere Medizin