title: Alendronate-induced atypical bone fracture: evidence that the drug inhibits osteogenesis.
abstract: OBJECTIVE
  Alendronate (ALN) is used for the treatment of post-menopausal osteoporosis. By reducing bone turnover, it increases bone mineral density. However, recent reports suggest an increased risk of atypical bone fractures after long-term ALN administration. Despite its well-known anti-osteoclastic activity, it is unclear whether ALN also suppresses human mesenchymal stem cell (hMSC)-mediated osteogenesis, thus possibly resulting in atypical bone fragility. We hypothesized that ALN does this and we look at its in vitro effects on osteogenesis.
  
  
  METHODS
  Morphological analysis, reverse transcriptase polymerase chain reaction, cell viability, alkaline phosphatase (ALP) activity and mineralization assays were investigated in hMSCs treated with a wide range of ALN.
  
  
  CONCLUSIONS
  After treatment with high concentrations of ALN for 3 and 7 days, cell viability was significantly reduced and cell morphology was altered. Osteogenic differentiation of hMSCs was also substantially suppressed as demonstrated by decreased ALP activity although ALN did not affect osteogenic-related genes tested. Furthermore, ALN at all concentrations tested drastically inhibited alizarin red S-positive mineralized matrix.
  
  
  CONCLUSIONS
  ALN has a strong inhibitory effect on hMSC-mediated osteogenesis by suppressing cell proliferation, osteoblast differentiation and function. The insight gained may help in the development of safer alternatives.
authors.affiliation: Thammasat University, Pathumthani, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Patntirapong
authors.forename: W
authors.initials: W
authors.lastname: Singhatanadgit
authors.forename: S
authors.initials: S
authors.lastname: Arphavasin
mesh_terms: D019386:Alendronate / Q000633:toxicity*; D050071:Bone Density Conservation Agents / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050723:Fractures, Bone / Q000139:chemically induced*; D006801:Humans; D066298:In Vitro Techniques; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D019386:Alendronate
keywords: alendronate; mesenchymal stem cell; mineralization; osteoblast differentiation; viability