ArticleJournal of orthopaedic translation2021
The effect of topical administration of simvastatin on entochondrostosis and intramembranous ossification: An animal experiment.
Article in Journal of orthopaedic translation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Effect of zoledronic acid combined with simvastatin on postoperative recovery of elderly patients with osteoporotic intertrochanteric fractures.Journal of orthopaedic surgery and research · 2026Article
- Overactivation of EGFR signaling in skeletal stem/progenitor cells promotes bone formation and repair.Theranostics · 2025Article
- A personalized biomimetic dual-drug delivery system via controlled release of PTHFrontiers in bioengineering and biotechnology · 2024Article
- Simvastatin-hydroxyapatite coatings prevent biofilm formation and improve bone formation in implant-associated infections.Bioactive materials · 2023Article
- Impact of High-Altitude Hypoxia on Bone Defect Repair: A Review of Molecular Mechanisms and Therapeutic Implications.Frontiers in medicine · 2022Review
- Glucocorticoid, Covid-19, bone and nerve repair.Journal of orthopaedic translation · 2021Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSimvastatin, a drug for lowering serum cholesterol, has been shown to enhance bone regeneration, but few studies have qualitatively and quantitatively tested its effect when used topically in different animal models. This study aims to investigate topical administration of simvastatin as a bone regeneration inducer by testing its effect on bone formation in both long tubular bone and flat bone defect, and the mechanism involved.
methodsTwo animal models were used for testing the effect of simvastatin on entochondrostosis and intramembranous ossification respectively. Simvastatin of different dosages combined with poly lactic acid were implanted in extreme radial defects of 12 adult male New Zealand rabbits. Bone formation was monitored using x-ray and CT-scan and measured using x-ray scales, pixel values and spiral CT-scan for 16 weeks before being subject to histological and immunohistochemistry examination. The result was compared with that of autograft and blank control groups. Simvastatin with thrombin and fibrin sealant were implanted in calvarial defects of three Rhesus monkeys and monitored for 18 weeks. Bone formation was compared between the simvastatin and the blank control group using spiral CT-scan and histological examination.
resultsBoth visual and quantitative measurements by x-ray and spiral CT-scan indicated significant bone formation in radial defects in all simvastatin groups and the autograft group whereas no bone formation was found in control groups. There was no significant difference in bone formation quantity between 100 mg simvastatin and autograft. Histological and immunohistochemistry examination indicated entochondrostosis in association with positive expression of BMP-2 and HIF-1 alpha. Spiral CT-scan and histological examination of calvarial defects of monkeys showed intramembranous ossification after simvastatin implantation. No change was found in the control group.
conclusionsTopical administration of simvastatin induces entochondrostosis and intramembranous ossification by enhancing expression of BMP-2 and HIF-1 alpha. The effect of simvastatin on bone regeneration is comparable to autograft. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Topical administration of simvastatin can repair bone defect in both long tubular bones and flat bones of rabbits and monkeys as effectively as autograft. Given that it is cheap, safe and already in clinical use, simvastatin might be considered as a bone regeneration inducer with great potential.
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