Red Yeast Rice Increases Bone Morphogenetic Protein-2 Expression and Enhances Fracture Healing Process in Delayed Union Models of Sprague-Dawley Rats: A Preclinical Study.

Abstract

Introduction: Delayed union management is both challenging and expensive. Statins, which are HMG-CoA reductase inhibitors, induce bone morphogenetic protein-2 (BMP-2) gene expression, which in turn increases bone formation. Red yeast rice contains monacolin, which has a similar activity to lovastatin as an HMG-CoA reductase inhibitor. Red-yeast rice is readily available and inexpensive. This study aimed to demonstrate the effectiveness of red yeast rice in enhancing fracture healing in a delayed union model through increased expression of BMP-2.

Materials and methods: This experimental animal study was conducted using 24 delayed union Sprague-Dawley (SD) rats divided into four groups (n=6 each), consisting of; the 4-weeks-given-red yeast rice extract group (4RYR), 2-weeks-given-red yeast rice extract group (2RYR), 4-weeks-control group (4C), and 2-weeks-control group (2C). The animals were euthanized in the second and fourth week. Immunohistochemical staining was used to assess BMP-2 expression using an Immunoreactive Score (IRS). The fracture healing process was evaluated using histomorphometry by measuring the fibrous area, cartilage area, and woven bone area percentage.

Results: In the 2RYR group, there was significantly higher BMP-2 expression (p=0.03), less fibrous area (p=0.05), and larger cartilage area (p= 0.04) than in the 2C group. In the 4RYR group, there was significantly higher expression of BMP-2 (p=0.011), larger woven bone area (p=0.01), and less fibrous area (p = 0.03) than in the 4C group. There was also a significantly smaller fibrous area (p=0.02), a larger cartilage area (p=0.05), and a larger woven bone area (p=0.04) in the 4RYR group than in the 2RYR group. The BMP-2 expression in the 2RYR group was as high as that in the 4RYR group.

Conclusion: Red yeast rice effectively improved fracture healing by increasing BMP-2 expression in a delayed-union model in SD rats.