Purpose of Review <p>The present review will examine bone disease in mastocytosis, analyze the existing literature on its management, and propose a strategy for osteoporosis treatment in systemic mastocytosis. This strategy is based on both the available scientific evidence and the experience gained at our expert center (CEREMAST).</p> Recent Findings <p>Systemic mastocytosis is a rare disorder, primarily affecting the bone and leading to osteoporosis, bone pain, and bone structural abnormalities. While traditionally described in indolent systemic mastocytosis, bone involvement is also observed in bone marrow mastocytosis. The true prevalence of systemic mastocytosis is likely underreported, highlighting the importance for clinicians to be familiar with the condition, particularly in cases of osteoporosis. Osteoporosis management typically involves bisphosphonates, with potential benefits from combining them with specific treatments like interferon in severe osteoporosis with vertebral fractures. The potential of new mast cell-targeting molecules to treat bone involvement needs to be demonstrated.</p> Summary <p>This review provides a guide for osteoporosis and bone pain management in systemic mastocytosis.</p>