Indolent Systemic Mastocytosis Presenting with Consecutive Vertebral Fragility Fractures despite Normal Bone Mineral...

Indolent systemic mastocytosis (ISM) is a rare clonal mast-cell disorder that may present with skeletal involvement, driven by mast-cell mediator-induced osteoclast activation. Vertebral fragility fractures can occur even in the presence of normal bone mineral density (BMD), making early diagnosis challenging.

A 56-year-old woman with a prior history of cutaneous mastocytosis and persistently elevated serum tryptase presented with acute thoracolumbar pain after minimal trauma. Initial imaging revealed a T11 compression fracture with normal BMD on dual-energy X-ray absorptiometry. Kyphoplasty resulted in symptomatic improvement. Ten weeks later, she developed a second atraumatic L1 vertebral fracture. Given the atypical fracture pattern and mastocytosis history, she underwent L1 kyphoplasty with concurrent osseous biopsy. Histopathology showed mast-cell infiltrates with CD25 expression, and molecular testing identified KIT D816V mutation. Bone marrow biopsy confirmed multifocal mast-cell infiltration, establishing a diagnosis of ISM. The patient was treated with intravenous bisphosphonates and multidisciplinary follow-up. At the last follow-up, she demonstrated pain resolution and no new fractures.

This case underscores that ISM may present solely with skeletal manifestations despite normal BMD. Mast-cell mediators, including tryptase, histamine, tumor necrosis factor-alpha, and interleukin-6 promote osteoclastogenesis and microarchitectural bone fragility. Kyphoplasty-guided biopsy is a key diagnostic opportunity in unexplained vertebral fractures.

ISM should be considered in patients with atypical vertebral fractures, particularly when BMD is normal. Serum tryptase, KIT mutation testing, and bone biopsy enable timely diagnosis and treatment to prevent further skeletal morbidity.