Introduction: A large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone morphogenetic protein-2 (BMP-2) is known to play an important role in the chondrogenesis of the IVD. Simvastatin is known to up-regulate the expression of BMP-2. Thus, we hypothesized that intradiscal injection of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD.
Methods: Disc injury was induced in 272 rats via 21-gauge needle puncture. After six weeks, injured discs were treated with simvastatin in saline or a hydrogel carrier. Rats were sacrificed at predetermined time points. Outcomes measures assessed were radiologic, histologic, and genetic. Radiologically, the MRI index (the number of pixels multiplied by the corresponding image densities) was determined. Histologically, disc spaces were read by three blinded scorers based on a previously used grading scale. Genetically, nuclei pulposus were harvested and polymerase chain reaction was run to determine relative levels of aggrecan and collagen type II gene expression.
Results: Radiologically, discs treated with 5 mg/ml simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks post-treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/ml simvastatin in hydrogel demonstrated improved grades in comparison with discs treated at higher doses. Genetically, discs treated with 5 mg/ml of simvastatin in hydrogel demonstrated higher gene expression of aggrecan and collagen type II than control.
Conclusions: Degenerate discs treated with 5 mg/ml simvastatin in a hydrogel carrier demonstrated radiographic and histologic features resembling normal, non-injured IVDs. In addition, gene expression of aggrecan and collagen type II (important constituents of the IVD extracellular matrix) was up-regulated in treated discs. Injection of simvastatin into degenerate IVDs may result in retardation of disc degeneration and represents a promising investigational therapy for the conservative treatment of DDD.
Patient Care: This study lays the groundwork for future research on using simvastatin for the treatment of degenerative disc disease.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the role BMPs have in disc disease; 2) Identify laboratory outcomes measures used in DDD research; and 3) Explain the role statins may have in treating DDD.