title: The effects of zoledronate on the survival and function of human osteoblast-like cells.
abstract: BACKGROUND
  Prolonged bisphosphonate treatment might suppress bone remodeling to the extent that normal bone repair is impaired. While this adverse side effect is usually ascribed to the negative effects of bisphosphonates on osteoclast survival and function, these effects on osteoblasts are still unclear.
  
  
  METHODS
  In the current study, we hypothesized that zoledronate (ZOL) at the μM level might present negative effects on osteoblast survival and function. In vitro analyses of proliferation, migration and differentiation were performed on human osteoblast-like cells.
  
  
  RESULTS
  Our results revealed that ZOL treatment dose- and time-dependently induced apoptosis of osteoblasts after concentrations had reached 10 μM (p < 0.001). The concentrations at which ZOL inhibited osteoblast migration by 50 % were between 10 and 15 μM. Moreover, there was a dose-dependent reduction in the extent of matrix mineralization, but without a concomitant inhibition of osteogenic differentiation in terms of secreted type I collagen and osteocalcin and of alkaline phosphatase activity per viable cell. Analyses of the expression of osteogenic genes confirmed that ZOL at the μM level had no effects on osteogenic differentiation of osteoblasts.
  
  
  CONCLUSIONS
  We concluded that ZOL at the μM level affected osteoblast survival and migration, but did not affect differentiation. The pathophysiological implications of ZOL at the μM level on skeletal disorders need to be investigated and clarified in the future researches.
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan. kc2672@gmail.com.|Chang Gung University College of Medicine, Taoyuan, Taiwan. kc2672@gmail.com.|, Present address: No. 6, West Section, Chia-Pu Road, Pu-Tz City Chiayi County, 61313, Taiwan. kc2672@gmail.com.
authors.forename: Kuo-Chin
authors.initials: KC
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.|Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Chin-Chang
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Po-Yao
authors.initials: PY
authors.lastname: Chuang
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Tien-Yu
authors.initials: TY
authors.lastname: Yang
mesh_terms: D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid