title: Local effects of malignancy on bone.
abstract: OBJECTIVE
  Skeletal-related complications occur commonly in many solid tumors including breast, prostate and lung cancer as well as multiple myeloma. In addition, malignancies and their associated treatment may result in bone loss or osteoporosis. This review will focus solely on recent data associated with metastatic bone disease with a focus on breast cancer, prostate cancer and multiple myeloma. Bone loss or osteoporosis associated with cancer will be covered in a separate article in this issue.
  
  
  RESULTS
  Recent progress in understanding the pathophysiology of bone metastases has pointed to several novel pathways: transforming growth factor beta; receptor activator of nuclear factor beta ligand and osteoprotegerin; and Wnt signaling pathways and associated factors such as dickkopf-1 and endothelin-1.
  
  
  CONCLUSIONS
  The identification of new pathways is important in metastatic bone disease from cancer and has allowed for the development of novel therapeutics aimed at preventing the devastating complications of bone metastases. Bisphosphonates remain the predominant therapy in use for the treatment and prevention of skeletal-related adverse effects from cancer.
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, Virginia, USA. sab2f@virginia.edu
authors.forename: Sue A
authors.initials: SA
authors.lastname: Brown
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Clines
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Guise
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004164:Diphosphonates / Q000627:therapeutic use; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D053244:Osteoprotegerin / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D050071:Bone Density Conservation Agents; C501126:DKK1 protein, human; D004164:Diphosphonates; D019332:Endothelin-1; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins