Tumor-associated cachexia is a multifactorial disease with progressive skeletal muscle loss irreversible by standard nutritional aid, ultimately resulting in functional impairment. In a very recent Editorial published in JBMR, Elena Tsourdi has highlighted several important aspects of tumor-associated cachexia, including the possibility of cachexia in nonmetastatic disease and the therapeutic prospects. Tsourdi specifically commented on an article by Pin and colleagues that has just been published in JBMR. Namely, Pin et al. examined the role of tumor-secreted RANKL in both bone loss and skeletal muscle atrophy in the setting of ovarian cancer. By using in vitro and in vivo experimental models, they found that elevated circulating RANKL was sufficient to cause skeletal muscle atrophy and bone resorption, whereas bone preservation by means of antiresorptive and anti-RANKL treatments concurrently benefited muscle mass and function in cancer cachexia. These findings support RANKL as a novel therapeutic target for the treatment of musculoskeletal complications associated with RANKL-expressing nonmetastatic cancers. Tsourdi also emphasized the importance of research on the largely neglected impact of nonmetastatic cancer on bone and muscle homeostasis, and pointed out the relevance of emerging knowledge on skeletal effects of adjuvant endocrine therapies of breast and prostate cancer and antiosteoporosis medications. In particular, denosumab, an antibody targeting human RANKL, is suitable both for osteoporosis treatment and for maintenance of bone mass in patients undergoing hormone ablation therapy for breast and prostate cancer. Clearly, there are new opportunities for an additional use of denosumab as a well-characterized FDA-approved antiresorptive drug to treat tumor cachexia, but further studies are warranted to confirm its efficacy in the management of muscle and bone defects in ovarian cancer.