Indolent Mastocytosis and Bone Health: Molecular Mechanisms and Emerging Treatment Options

Mastocytosis is a heterogeneous group of disorders, distinguished by the monoclonal proliferation of mast cells (MCs) in one or more organs. While cutaneous mastocytosis (CM) is restricted to the skin, systemic mastocytosis (SM) presents with high MC infiltration of various organs. Indolent systemic mastocytosis (ISM) is the most common form in individuals with adult-onset of the disease. Bone health impairment is present in the vast majority of patients, ranging from osteoporosis to osteosclerosis, often presenting with fragility fractures. In this review, we comprehensively examine the impact of ISM on bone health, with particular emphasis on the molecular and cellular mechanisms underlying skeletal involvement, the clinical heterogeneity of bone manifestations, and the limitations of current diagnostic tools, while also evaluating emerging therapeutic strategies that target both MC activity and bone remodeling pathways.