title: The effects of bisphosphonates on osteoblasts in vitro.
abstract: OBJECTIVE
  The purpose of this study was to test the effects of bisphosphonates on osteoblast viability and function.
  
  
  METHODS
  Primary rat osteoblasts were cultured in normal media or media containing increasing concentrations of 2 bisphosphonates, alendronate and zoledronate. Enzyme-linked immunoabsorbent assays (ELISAs) were used to measure interleukin (IL)-6, transforming growth factor (TGF) beta1, and receptor activator of nuclear factor kappaB ligand (RANKL) expression in supernatants after 24, 48, and 72 h. Live and necrotic cell numbers were assessed with trypan blue assays.
  
  
  RESULTS
  As drug concentrations increased, cell viability decreased significantly. The ELISAs revealed significant increases in TGF-beta1 in treatment groups, but no significant change in RANKL or IL-6.
  
  
  CONCLUSIONS
  High concentrations of alendronate and zoledronate were cytotoxic, decreasing cell viability at 72 h. Transforming growth factor beta1 increased even as viability decreased, suggesting a mechanism for bisphosphonate action. These data suggest that lower concentrations of bisphosphonates may have therapeutic benefits without the cytotoxic effects which may result in osteonecrosis.
authors.affiliation: Department of Diagnostic Science, Baylor College of Dentistry, Texas A&M Health Science Center, Dallas, Texas 75246, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Naidu
authors.forename: Paul C
authors.initials: PC
authors.lastname: Dechow
authors.forename: Robert
authors.initials: R
authors.lastname: Spears
authors.forename: John M
authors.initials: JM
authors.lastname: Wright
authors.forename: Harvey P
authors.initials: HP
authors.lastname: Kessler
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Opperman
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004164:Diphosphonates / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007093:Imidazoles / Q000008:administration & dosage / Q000633:toxicity; D015850:Interleukin-6 / Q000096:biosynthesis; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D053245:RANK Ligand / Q000096:biosynthesis; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D015850:Interleukin-6; D053245:RANK Ligand; D053773:Transforming Growth Factor beta1; D000077211:Zoledronic Acid; D019386:Alendronate