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Cancer-Associated Bone Disease; Role of Obesity and Adipokines

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Obesity and cancer-associated bone disease

Bone is commonly affected in cancer from the primary disease, or from therapies. Finding novel therapies necessitates the elucidation of the underlying mechanisms.


Cancer-associated bone disease is a major cause of morbidity and mortality for patients with the haematological malignancy multiple myeloma. Also, prostate cancer often generates skeletal metastases and anti-cancer therapies could lead to bone fragility. To identify new therapeutic targets against this secondary condition, it is necessary to dissect the complex mechanisms within the bone marrow that promote both tumour growth and the associated bone disease. There is increasing evidence to suggest that obesity and adipokines are associated with malignancy. However, their precise role in bone metastases has not been fully elucidated. With this in mind, scientists of the EU-funded CABROA (Cancer-associated bone disease; role of obesity and adipokines) project utilised in vivo models that combined cancer-induced bone disease with diet-induced obesity. Their work demonstrated that diet-induced obesity created a permissive environment for the development of a myeloma-like condition. This type of obesity was strongly associated with tumour burden within bone as well as bone loss. Although this phenotype was linked to changes in insulin-like growth factor 1 levels, there was no myeloma development in a genetic obesity model. To elucidate the effect of bone marrow adiposity in cancer-induced bone disease further, researchers employed genetic models of adiposity. Additionally, they performed a high-throughput analysis of adipokines and adiposity-related factors in patients with prostate cancer or myeloma. Their findings unveiled a number of novel adipokines that were deregulated in cancer-induced bone disease and warrant further investigation. Future work aims to delineate the precise function of one novel factor associated with prostate cancer bone metastasis. From a therapeutic perspective, the consortium demonstrated the protective effect of the anti-diabetic agent metformin in cancer-induced bone disease. Given that metformin regulates adipokines and adipocytes, it further validates the association of adiposity and adipokines in the pathogenesis of the skeletal metastases. These findings could be used to develop novel effective therapeutic approaches.


Obesity, cancer-associated bone disease, multiple myeloma, prostate cancer, adipokine, insulin-like growth factor 1, metformin

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