Endocrine manifestations of systemic mastocytosis in bone.

Systemic Mastocytosis (SM) is characterized by accumulation of clonal, neoplastic proliferations of abnormal mast cells (MC) in one or more organ system other than skin. Presence of these multifocal clusters of abnormal mast cells is an essential feature of SM. Frequently associated with D816V (KIT) mutation, the presence of this mutation and elevated serum tryptase are minor criteria for diagnosis. SM manifestations depend on the degree of mast cell proliferation, activation and degranulation. SM has a variable prognosis and presentation, from indolent to "smoldering" to life-threatening disease. Bone manifestations of SM include: osteopenia with or without lytic lesions, osteoporosis with or without atraumatic fracture, osteosclerosis with increased bone density, and isolated lytic lesions. Male sex, older age, higher bone resorption markers, lower DKK1 level, lower BMD, absence of urticaria pigmentosa, and alcohol intake are all associated with increased risk of fracture. Treatment of SM is generally palliative. Most therapy is symptom-directed; and, infrequently, chemotherapy for refractory symptoms is indicated. Anti-histamines may alleviate direct bone effects of histamine. Bisphosphonates, including alendronate, clodronate, pamidronate and zoledronic acid are recommended as a first line treatment of SM and osteoporosis. Interferon α may act synergistically with bisphosphonates. As elevation of RANKL and OPG is reported in SM, denosumab could be an effective therapy for bone manifestations of SM.