title: Zoledronic acid at the time of castration prevented castration-induced bone metastasis in mice.
abstract: Androgen deprivation therapy (ADT) is known to cause bone loss in a majority of patients with castration-resistant prostate cancer (CRPC). A study published in this issue of Endocrine-Related Cancer by Ottewell and colleagues shows that ADT increased bone resorption and triggered growth of disseminated prostate cancer (CaP) cells to form bone metastasis using an in vivo model. However, prevention of bone decay by weekly administration of zoledronic acid (ZOL) at the time of castration prevented ADT-induced tumor growth in bone. Recently, two publications from Japan have demonstrated that ZOL combined with ADT improved outcomes for patients with treatment-naïve CaP with bone metastasis. The mechanistic cause for these patients having an improved overall survival compared with those who were treated with ZOL after ADT initiation or before metastasis development was never explained. Ottewell and colleague's study now suggests that it is the bone loss caused by ADT that promoted bone metastasis, and if ZOL is administered at the time of ADT initiation, it would prevent this bone loss and prolong skeletal-related event-free survival.
authors.affiliation: Department of UrologyUniversity of California Davis School of Medicine, 4860 Y Street, Suite 3500, Sacramento, California 95817, USADepartment of Biochemistry and Molecular MedicineUniversity of California Davis, Sacramento, California, USAVA Northern California Health Care SystemSacramento, California, USA Department of UrologyUniversity of California Davis School of Medicine, 4860 Y Street, Suite 3500, Sacramento, California 95817, USADepartment of Biochemistry and Molecular MedicineUniversity of California Davis, Sacramento, California, USAVA Northern California Health Care SystemSacramento, California, USA Department of UrologyUniversity of California Davis School of Medicine, 4860 Y Street, Suite 3500, Sacramento, California 95817, USADepartment of Biochemistry and Molecular MedicineUniversity of California Davis, Sacramento, California, USAVA Northern California Health Care SystemSacramento, California, USA paramita.ghosh@ucdmc.ucdavis.edu.
authors.forename: Paramita M
authors.initials: PM
authors.lastname: Ghosh
authors.affiliation: Department of UrologyUniversity of California Davis School of Medicine, 4860 Y Street, Suite 3500, Sacramento, California 95817, USADepartment of Biochemistry and Molecular MedicineUniversity of California Davis, Sacramento, California, USAVA Northern California Health Care SystemSacramento, California, USA Department of UrologyUniversity of California Davis School of Medicine, 4860 Y Street, Suite 3500, Sacramento, California 95817, USADepartment of Biochemistry and Molecular MedicineUniversity of California Davis, Sacramento, California, USAVA Northern California Health Care SystemSacramento, California, USA.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Gao
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000556:secondary*; D001862:Bone Resorption / Q000517:prevention & control*; D002369:Castration; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: androgen deprivation therapy; bone loss; prostate cancer; zoledronic acid