Sclerostin may serve as a useful marker for identifying advanced stages of mastocytosis and associated bone disease, particularly in advanced systemic mastocytosis (SM), according to results from a study published recently in Scientific Reports.
Patients with severe mastocytosis demonstrated significantly elevated sclerostin levels, especially in patients with advanced SM and sclerotic changes in the spongy bone. These results provide important insight into the progression of mastocytosis and its effect on bone health.
What is SM?
Systemic mastocytosis (SM) is a rare hematological disease characterized by mast cells that are overactive and accumulate in different parts of the body such as the bone marrow, liver, spleen, gastrointestinal tract and lymph nodes.
This study involved 39 patients diagnosed with mastocytosis, with a median age of 49 years. The most common diagnosis was indolent SM (46.2%), and advanced cases included advanced SM (20.5%) and SM with associated hematologic neoplasm (2.6%).
Read more about SM testing and diagnosis
Bone complications, such as spinal fractures, were reported in 17.9% of participants. Importantly, 85% of patients were carriers of the KIT D816V mutation, which is commonly linked to mastocytosis.
For patients, the results underlined the importance of early detection and monitoring of sclerostin levels to assess the risk of bone complications. Targeted therapies addressing elevated sclerostin or inflammatory pathways could improve outcomes for those with advanced mastocytosis. Further research is needed to clarify the role of sclerostin in progression of disease and explore its potential as a therapeutic target.
“Mast cells in vitro are capable of secretion of sclerostin and its level correlates with some radiological and clinical features of bone disease in SM patients,” the authors said. They added: “It suggests the impact of sclerostin on the complex process of bone remodeling in patients with mastocytosis and justify the need for further research using an experimental bone formation model and larger patient groups.”
Analysis of cultures of human mast cells revealed that neoplastic mast cells secrete sclerostin, a protein implicated in bone remodeling. Stimulation with interleukin-6 significantly increased sclerostin levels, suggesting a potential role for inflammatory processes in the progression of mastocytosis-related bone disease.
Plasma concentrations of sclerostin were notably higher in patients with advanced SM, SM with associated hematologic neoplasm and smoldering SM compared to those with less advanced forms such as indolent SM and cutaneous mastocytosis.
Elevated sclerostin levels were strongly associated with bone sclerosis observed in low-dose computed tomography scans. Patients with increased sclerosis had median sclerostin concentrations of 37 pmol/L, compared to 15.2 pmol/L in those without such bone changes. In addition, correlations were found between sclerostin levels and interleukin-6, while an inverse relationship was noted with alkaline phosphatase activity, highlighting sclerostin’s potential as a biomarker for severity of disease.
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