Muscle and Bone Defects in Metastatic Disease

Abstract

Purpose of review: The present review addresses most recently identified mechanisms implicated in metastasis-induced bone resorption and muscle-wasting syndrome, known as cachexia.

Recent findings: Metastatic disease in bone and soft tissues is often associated with skeletal muscle defects. Recent studies have identified a number of secreted molecules and extracellular vesicles that contribute to cancer cell growth and metastasis leading to bone destruction and muscle atrophy. In addition, alterations in muscle microenvironment including dysfunctions in hepatic and mitochondrial metabolism have been implicated in cancer-induced regeneration defect and muscle loss. Moreover, we review novel in vitro and animal models including promising new drug candidates for bone metastases and cancer cachexia. Preservation of bone health could be highly beneficial for maintaining muscle mass and function. Therefore, a better understanding of molecular pathways implicated in bone and muscle crosstalk in metastatic disease may provide new insights and identify new strategies to improve current anticancer therapeutics.

Keywords: Bone destruction; Cachexia; Metastasis; Muscle weakness; Secreted factors.

Fig. 1

Bone-muscle crosstalk in bone metastasis. Bone-derived osteokines and muscle-derived myokines mediate the bone-muscle interactions in physiological and pathological conditions. In bone metastasis, several cytokines are released from the bone matrix (e.g., TGF-β) that impair muscle function and promote tumor growth. Furthermore, local such as RANKL promote bone destruction and reduce muscle strength. Thus, preventing pathological bone resorption could be an effective therapeutic strategy to preserve not only the bone but also muscle health in metastasis