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

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

doi:10.1007/s00223-015-9969-5

Cited by 16 publications

(6 citation statements)

References 31 publications

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“…The relationship between DKK1 and OPG has also been demonstrated in OB precursors [14]. In agreement with our findings, it was demonstrated that high DKK1 serum levels correlate with CTX amounts in multiple myeloma, in chronic glucocorticoid treatment [22,30], in mastocytosis [31] and in rheumatoid arthritis [32]. In patients with OI bone turnover is generally increased but an increase also in RANKL/OPG ratio and its positive correlation with DKK1 could confirm in vivo the prevalence of bone resorption showed in vitro and the possible role of DKK1.…”

Section: Discussionsupporting

confidence: 91%

Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α

et al. 2016

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Section: Discussionsupporting

confidence: 91%

Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α

et al. 2016

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“…Confirming this, bone formation and resorption markers were found to be increased in SM patients (153). However, other authors reported increased serum levels of dickkopf 1 and sclerostin, both inhibitors of the osteoanabolic Wnt signaling pathway, indicating reduced bone formation (154,155). IL-6 levels are also increased in SM, and correlate with the severity of the symptoms and bone loss (155,156).…”

Section: The Role Of Mast Cells In Bone Disorders Osteoporosismentioning

confidence: 72%

The Role of Mast Cells in Bone Metabolism and Bone Disorders

et al. 2020

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Mast cells (MCs) are important sensor and effector cells of the immune system that are involved in many physiological and pathological conditions. Increasing evidence suggests that they also play an important role in bone metabolism and bone disorders. MCs are located in the bone marrow and secrete a wide spectrum of mediators, which can be rapidly released upon activation of mature MCs following their differentiation in mucosal or connective tissues. Many of these mediators can exert osteocatabolic effects by promoting osteoclast formation [e.g., histamine, tumor necrosis factor (TNF), interleukin-6 (IL-6)] and/or by inhibiting osteoblast activity (e.g., IL-1, TNF). By contrast, MCs could potentially act in an osteoprotective manner by stimulating osteoblasts (e.g., transforming growth factor-β) or reducing osteoclastogenesis (e.g., IL-12, interferon-γ). Experimental studies investigating MC functions in physiological bone turnover using MC-deficient mouse lines give contradictory results, reporting delayed or increased bone turnover or no influence depending on the mouse model used. By contrast, the involvement of MCs in various pathological conditions affecting bone is evident. MCs may contribute to the pathogenesis of primary and secondary osteoporosis as well as inflammatory disorders, including rheumatoid arthritis and osteoarthritis, because increased numbers of MCs were found in patients suffering from these diseases. The clinical observations could be largely confirmed in experimental studies using MC-deficient mouse models, which also provide mechanistic insights. MCs also regulate bone healing after fracture by influencing the inflammatory response toward the fracture, vascularization, bone formation, and callus remodeling by osteoclasts. This review summarizes the current view and understanding of the role of MCs on bone in both physiological and pathological conditions.

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“…The PTH analogue teriparatide may promote further proliferation of mast cells and has not been recommended in this setting ( 9 ). Dickkopf-1 (DKK1) and sclerostin, receptor inhibitors of the Wnt pathway, have been studied in patients with SM, with DKK1 levels appearing to be elevated in comparison to controls but not sclerostin ( 17 ). It is thus unclear whether the Wnt/β-catenin pathway plays a significant role in the pathophysiology of SM.…”

Section: Treatment Of Osteoporosis In Systemic Mastocytosismentioning

confidence: 99%

Skin and bones: systemic mastocytosis and bone

Wang

Seibel

2023

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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Summary We report the case of a 69-year-old female with systemic mastocytosis, diagnosed based on widespread pigmented papules and macules, elevated serum tryptase levels and confirmatory skin and bone marrow biopsy, on a background of osteoporosis. A CT demonstrated multiple sclerotic lesions within lumbar vertebral bodies, sacrum and ileum, with surrounding osteolysis but no obvious compression fractures. She was treated with the RANK-L inhibitor denosumab, resulting in significant bone mineral density gain over the following 5 years. However, her serum tryptase levels gradually increased during this period despite treatment with the multikinase inhibitor, midostaurin. It is thus conceivable that her rapid increase in bone mineral density may be partly contributed by a predominance of pro-osteoblastic mediators released by abnormal mast cells, suggestive of more advanced disease. This case highlights the complexities of systemic mastocytosis-related bone disease and the interplay of numerous mediators contributing to a phenotype of both increased bone resorption and formation. Learning points Systemic mastocytosis is a neoplastic disease of mast cells characterized by abnormal proliferation and accumulation in the skin and other organs. It is most frequently associated with the somatic gain-of-function KIT D816V mutation. Systemic mastocytosis should be suspected in patients presenting with not only cutaneous symptoms suggestive of mast cell degranulation such as anaphylaxis, flushing or urticaria but also unexplained osteoporosis and gastrointestinal and constitutional symptoms. The prevalence of osteoporosis in systemic mastocytosis is high. Mast cell activation leads to the secretion of numerous chemical mediators which either promote or inhibit osteoclastic and/or osteoblastic activity, with the balance usually in favour of increased bone resorption. However, in advanced diseases with high mast cell burden, mast-cell-derived cytokines and mediators may promote osteoblastic activity, leading to osteosclerosis and apparent increases in bone mineral density. Treatment of osteoporosis in systemic mastocytosis involves antiresorptive therapy with bisphosphonates and more recently, denosumab. There are limited data on the role of osteoanabolic agents.

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

Cited by 16 publications

References 31 publications

Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α

Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α

The Role of Mast Cells in Bone Metabolism and Bone Disorders

Skin and bones: systemic mastocytosis and bone

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