title: Bone Metastasis from Renal Cell Carcinoma.
abstract: About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The "vicious cycle" hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. scarchenone@yahoo.com.tw.|Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. scarchenone@yahoo.com.tw.|Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan. scarchenone@yahoo.com.tw.|Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. scarchenone@yahoo.com.tw.
authors.forename: Szu-Chia
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. kuopolin@seed.net.tw.|Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan. kuopolin@seed.net.tw.
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: bone metastasis; bone turnover markers; molecular mechanisms; renal cell carcinoma; therapies