Bone Metastases: Systemic Regulation and Impact on Host

Advanced cancers frequently metastasize to bone and disrupt normal bone remodeling to cause bone destruction. Bone metastases are incurable and result in significant morbidity: Pain, fracture, hypercalcemia, spinal cord compression, and muscle weakness. The associated muscle weakness may occur prior to or in the absence of cachexia. Tumor-induced bone destruction causes the release of growth factors that can fuel tumor progression in bone. These factors can also act systemically to cause muscle weakness. The resulting muscle dysfunction adds to cancer-associated morbidity and can increase the risk of falls and fractures in patients with bone metastases. In this review, we discuss the mechanisms by which bone metastases can induce muscle weakness and potential ways to identify and treat cancer-induced systemic dysfunction.