Co- and triple-culture systems mimicking the marrow microenvironment revealed that MM-induced osteoclast formation was partially blocked by BDNF-neutralizing antibody and was nearly completely blocked by OPG, revealing that the significant effects of MM-derived BDNF on osteoclastogenesis may occur through MM-stromal interactions that upregulate RANKL expression. Here, BDNF is linked to Miyoshi myopathy.