Biomedicines (Aug 2022)

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

DOI
https://doi.org/10.3390/biomedicines10081915
Journal volume & issue
Vol. 10, no. 8
p. 1915

Abstract

Read online

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.

Keywords