Alendronate-induced atypical bone fracture: evidence that the drug inhibits osteogenesis.

Abstract

WHAT IS KNOWN AND 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.

RESULTS AND DISCUSSION:

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.

WHAT IS NEW AND CONCLUSION:

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: S Patntirapong, W Singhatanadgit, S Arphavasin
• Journal: Journal of clinical pharmacy and therapeutics (J Clin Pharm Ther) Vol. 39 Issue 4 Pg. 349-53 (Aug 2014) ISSN: 1365-2710 [Electronic] England
• PMID: 24661151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Bone Density Conservation Agents
• Alendronate

Topics

• Alendronate (toxicity)
• Bone Density Conservation Agents (toxicity)
• Cell Differentiation (drug effects)
• Cell Proliferation (drug effects)
• Fractures, Bone (chemically induced)
• Humans
• In Vitro Techniques
• Mesenchymal Stem Cells (cytology, drug effects)
• Osteogenesis (drug effects)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors