Anabolic Effects of a Novel Simvastatin Derivative on Treating Rat Bone Defects

Tien Ching Lee, Hui Ting Chen, I. Chun Tai, Li Ting Kao, Ming Hsin Hung, Chung Hwan Chen, Yin Chih Fu, Yan Hsiung Wang, Chih Ming Kao, Je Ken Chang, Mei Ling Ho*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Large bone defects may develop fracture nonunion, leading to disability and psychosocial burdens. Bone grafting with anabolic agents is a good autografting alternative. Simvastatin, as a cholesterol-lowering agent worldwide, is proven to enhance osteogenesis. Considering its dose-dependent adverse effects, we developed a simvastatin derivative, named KMUHC-01, which has bone anabolic capacity and lower cytotoxicity than simvastatin. We hypothesize that KMUHC-01 could help bone formation in bone-defect animal models. We used rat models of critical calvarial and long-bone defects to evaluate the effects of KMUHC-01 and simvastatin on biological changes at the bone defect through histology, immunohistology, and mechanical testing using three-point bending and evaluated the new bone formation microstructure through microcomputed tomography analysis. The newly formed bone microstructure at the calvarial defect site showed a significantly improved trabecular bone volume in the KMUHC-01 1-μM group compared with that in the control and simvastatin groups. The biomechanical study revealed a significantly increased maximal strength in the KMUHC-01 1-μM group compared with that in the control group. KUMHC-01, as a simvastatin derivative, showed a great anabolic effect in promoting bone defect healing. However, further studies will be conducted to prove the bioavailability and bone-forming efficacy of KMUHC-01 via systemic administration.

Original languageEnglish
Article number1915
JournalBiomedicines
Volume10
Issue number8
DOIs
StatePublished - Aug 2022

Keywords

  • bone defect
  • bone regeneration
  • drug
  • osteogenesis
  • simvastatin

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