Bone Loss, Osteoporosis, and Skeletal Fragility: Hidden Consequences of Cancer Cachexia

Cancer cachexia (CC) is a devastating, multi-organ syndrome historically defined by the progressive wasting of skeletal muscle and adipose tissue. However, emerging evidence suggests that the skeletal system is also a major, yet underappreciated target of this catabolic state. While bone loss in oncology is primarily attributed to skeletal metastasis or cancer treatment-induced bone loss (CTIBL), clinical and preclinical data has increasingly demonstrated that tumor and host-derived systemic signals can drive severe bone deterioration even in non-metastatic disease. This review synthesizes current information available on bone loss, osteopenia, and skeletal decline in the context of CC, with a specific focus on non-metastatic disease. By examining the available literature, we argue that bone loss is a “hidden” yet fundamental systemic manifestation of the cachectic state. Furthermore, we aim to highlight how concurrent muscle and bone deterioration (osteosarcopenia) dramatically worsens prognosis in several different cancers in both the adult and pediatric populations. Ultimately, this review highlights the potential contribution of cancer cachexia to osteoporosis and skeletal fragility, supporting the need for greater clinical awareness, improved musculoskeletal screening, and the development of targeted therapeutic strategies.