Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis

Abstract

Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown. To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis. A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n= 46), (2) significant bone loss (n= 47), and (3) diffuse bone sclerosis (n= 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis. Bone loss was associated with significantly higher levels of serum baseline tryptase (P= .01), IFN-γ (P= .05), IL-1β (P= .05), and IL-6 (P= .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P< .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P= .01), together with lower IFN-γ (P= .03) and RANK-ligand (P= .04) plasma levels versus healthy bone cases. SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.