The routine measurement of bone remodeling biomarkers should be performed in all patients with systemic mastocytosis (SM), according to findings from a cross-sectional study published in The Journal of Allergy and Clinical Immunology: In Practice.

In patients with SM, tissue accumulation of clonal mast cells often includes bone involvement. Although several mast cell mediators, such as receptor activator of nuclear factor κ-β ligand (RANKL) and interleukin (IL)-6, have been linked with bone loss in individuals with SM, data on the role played by mediators other than tryptase on diffuse bone sclerosis are lacking.

The researchers sought to explore the potential relationship between cytokine and bone remodeling markers with bone disease in patients with SM. The objective of the study was to identify unique biomarker profiles of bone loss and osteosclerosis in the plasma of adults with SM, which might lead to earlier diagnoses and an improved understanding of the pathogenesis of bone disease in these individuals.

Study inclusion criteria were as follows:

  • Aged more than 18 years
  • Diagnosis of SM
  • Full clinical and laboratory assessment performed at the Spanish Reference Center for Mastocytosis
  • Plasma samples obtained and frozen at -80⁰ C, prior to the administration of any cytoreductive medication.

At SM diagnosis, plasma concentrations of cytokines and serum baseline tryptase (sBT), along with bone turnover marker levels, were calculated. Of the 120 participants, 58 were male. The median patient age was 46 years (range, 36-55 years).

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Results showed that 39% (47 of 120) of the participants exhibited significant loss of bone mass, 23% (27 of 120) of the patients had diffuse bone sclerosis, and 38% (46 of 120) of the participants demonstrated no evidence of bone disease. Interestingly, anaphylaxis (P =.004), atopy (P =.004), and Hymenoptera venom allergy (P =.03) all were reported significantly less often among patients with diffuse bone sclerosis than among participants in the other 2 groups.

Bone loss was linked with significantly higher levels of sBT (P =.01), interferon-γ (IFN-γ; P =.05), IL-1β (P =.05), and IL-6 (P =.05) compared with concentrations observed in patients with healthy bone. Additionally, compared with patients with no evidence of bone disease,  those with diffuse bone sclerosis exhibited significantly higher levels of sBT
(P <.001), C-terminal telopeptide (P <.001), amino-terminal propeptide of type 1 procollagen (P <.001), osteocalcin
(P <.001), bone alkaline phosphatase (P <.001), osteopontin (P <.01), and the chemokine ligand 5/regulated upon activation normal: T-cell expressed and secreted (CCL5/RANTES) chemokine (P =.01), along with significantly lower plasma levels of IFN-γ (P =.03) and RANKL (P =.04).

“Further longitudinal long-term studies in large cohorts of [patients with SM] and age- and sex-matched controls are needed for a more in-depth understanding of the role of these biomarkers in the development of bone disease in SM and the underlying mechanisms involved,” the authors concluded.


Rama TA, Henriques AF, Matito A, et al. Bone and cytokine markers associated with bone disease in systemic mastocytosis. J Allergy Clin Immunol Pract. Published online February 18, 2023. doi:10.1016/j.jaip.2023.02.007