Because osteoclasts are primarily responsible for bone loss in SM, disphosphonates have also been recommended.26 Unfortunately, patients with SM do not tolerate diphosphonate infusions well and commonly experience worsening digestive symptoms as well as more frequent and severe acute phase responses.10 Denosumab, an anti-RANKL monoclonal antibody is currently being studied to treat SM-related bone loss related to SM with positive results.10 Palliative radiation therapy has been used for decreasing severe bone pain.26 This evidence concerns the gene TNFSF11 and systemic mastocytosis.