TNFSF11 and systemic mastocytosis: In fact, denosumab appears to be a valid alternative for treating bone loss even in ISM patients intolerant to bisphosphonates, where the risk of side effects and new fractures is minimal, as observed by Orsolini et al. The purpose of this study was to investigate the therapeutic effect of denosumab, an anti-RANKL monoclonal antibody, for the treatment of bone loss in patients with indolent systemic mastocytosis intolerant to bisphosphonates.