(12.02) Systemic Mastocytosis, a Rare Cause of Secondary Osteoporosis

Mastocytosis is a rare neoplastic disease that results in pathologic accumulation of mast cells within one or more organ systems. Mastocystosis encompasses a spectrum of presentations that ranges from the milder cutaneous mastocytosis (CM) to the most severe mast cell leukemia. Indolent systemic mastocytosis (ISM) exists on the milder end of the spectrum while still causing significant clinical disease.  Signs and symptoms of allergic reactions and anaphylaxis are well recognized in ISM, while other consequences of the disease may be clinically silent or not recognized as symptoms of ISM until later in the disease process. One such complication of ISM is osteopenia/osteoporosis which occurs in approximately 30% of ISM patients. Early diagnosis and treatment of both ISM and osteoporosis is necessary to prevent comorbidity in this population.

Case(s) Description :

A 29-year-old man presented with a vertebral burst fracture after a ground level fall. Biochemical evaluations revealed normal TSH, CMP, PTH, 24-hr urine calcium, but elevated serum tryptase. Presence of a fragility fracture prompted further testing to include bone marrow biopsy and DEXA scan. Bone marrow biopsy was diagnostic for systemic mastocystosis with KIT D816V + point mutation. DEXA scan confirmed osteoporosis with spine bone mineral density of 0.632 g/cm² (Z-Score -4.2) with osteopenia of the hip and radius. He started treatment with Avipritinib (PDGFR Inhibitor) for the ISM and infusions of zoledronic acid for osteoporosis without adverse effects.

Discussion :

Bony disease in mastocytosis is common and occurs primarily through activation of osteoclasts via release of multiple vasoactive mediators from mast cells including histamine, IL-6, and TNF- α. Osteopenia/osteoporosis are the most common bone disease caused by ISM. Trabecular bone is most affected, with highest incidence in the spine and higher rates of vertebral fractures as seen in this patient. Screening for osteoporosis in these patients should be done regardless of age, with optimization of calcium and Vitamin D intake and aggressive treatment of osteoporosis, if present. Early diagnosis and management are the keys to preventing morbidity and maintaining a high quality of life in patients with mastocytosis.