title: Alendronate alters osteoblast activities.
abstract: OBJECTIVE
  Due to accumulation in the bone matrix and a half-life of at least 10 years, it is important to understand the cellular impact of bisphosphonates (BPs). This study assessed the effects of alendronate (ALN) on human primary osteoblasts.
  
  
  METHODS
  Osteoblasts were incubated with ALN (5, 20 and 100 μM), and both cells and cell culture media were harvested after d 1, 3, 7 or 14. Proliferation was evaluated by3H-thymidine incorporation and tetrazolium dye (MTT) colorimetric assay, and viability by the lactate dehydrogenase (LDH) activity in the medium. Differentiation was evaluated using protein Luminex multiplex assays and RT-PCR.
  
  
  RESULTS
  ALN had no significant effects on cell viability. The lower concentrations enhanced the proliferation, whereas 100 μM diminished the proliferation. mRNA expression of osteocalcin (OC), alkaline phosphatase (ALP) and α-1 type 1 collagen were reduced, whereas ALN enhanced the expression of leptin mRNA and the secretion of interleukin-8 (IL-8) and regulated on activation normal T cell expressed and secreted (RANTES).
  
  
  CONCLUSIONS
  ALN enhanced the secretion of immune factors from human osteoblasts. Combined with a lower rate of proliferation and a decline in differentiation, this indicates that higher dosages or accumulation may cause undesirable local changes in bone.
authors.affiliation: a Department of Oral Surgery and Oral Medicine, Faculty of Dentistry , University of Oslo , Oslo , Norway.
authors.forename: Tormod B
authors.initials: TB
authors.lastname: Krüger
authors.affiliation: a Department of Oral Surgery and Oral Medicine, Faculty of Dentistry , University of Oslo , Oslo , Norway.
authors.forename: Bente B
authors.initials: BB
authors.lastname: Herlofson
authors.affiliation: b Department of Biomaterials, Faculty of Dentistry , University of Oslo , Oslo , Norway.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Landin
authors.affiliation: b Department of Biomaterials, Faculty of Dentistry , University of Oslo , Oslo , Norway.
authors.forename: Janne E
authors.initials: JE
authors.lastname: Reseland
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000187:drug effects; D024042:Collagen Type I / Q000187:drug effects; D000090602:Collagen Type I, alpha 1 Chain; D006801:Humans; D016209:Interleukin-8 / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D020738:Leptin / Q000032:analysis; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000187:drug effects
chemical_list: D050071:Bone Density Conservation Agents; C483024:CCL5 protein, human; C508606:CXCL8 protein, human; D018946:Chemokine CCL5; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016209:Interleukin-8; D020738:Leptin; D015675:Osteocalcin; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D019386:Alendronate
keywords: Bisphosphonates; bone; cytotoxic; osteonecrosis