Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease.

BACKGROUND CONTEXT: 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 chondrogenesis of the IVD. Simvastatin is known to upregulate 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. PURPOSE: The purpose of the present study was to develop a novel conservative treatment for DDD and related discogenic back pain. STUDY DESIGN/SETTING: The setting of this study is the laboratory investigation. METHODS: Disc injury was induced in 272 rats via 21-ga needle puncture. After 6 weeks, injured discs were treated with simvastatin in a saline or hydrogel carrier. Rats were sacrificed at predetermined time points. Outcome measures assessed were radiologic, histologic, and genetic. Radiologically, the magnetic resonance imaging (MRI) index (number of pixels multiplied by the corresponding image densities) was determined. Histologically, disc spaces were read by three blinded scorers using a previously described histologic grading scale. Genetically, nuclei pulposi were harvested, and polymerase chain reaction was run to determine relative levels of aggrecan, collagen type II, and BMP-2 gene expression. RESULTS: Radiologically, discs treated with 5 mg/mL of simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks after treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated improved grades compared 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 of simvastatin in a hydrogel carrier demonstrated radiographic and histologic features resembling normal noninjured IVDs. In addition, the gene expression of aggrecan and collagen type II (important constituents of the IVD extracellular matrix) was upregulated in treated discs. Injection of simvastatin into degenerate IVDs may result in retardation of disc degeneration and represents a promising investigational therapy for conservative treatment of DDD.

Schmorl's nodes.

INTRODUCTION: First described in 1927, a Schmorl's node (SN) is the herniation of nucleus pulposus (NP) through the cartilaginous and bony end plate into the body of the adjacent vertebra. SNs are common findings on imaging, and although most SNs are asymptomatic, some have been shown to become painful lesions. In this manuscript, we review the literature regarding the epidemiology, clinical presentation, pathogenesis, imaging, and management of SNs. MATERIALS AND METHODS: Using databases from the US National Library of Medicine and the National Institutes of Health, relevant articles were identified. RESULTS: While several theories regarding the pathogenesis of SNs have been proposed, an axial load model appears to have the greatest supporting evidence. Symptomatic SNs are thought to be due to the inflammatory response solicited by the herniation of NP into the well-vascularized vertebral body. Management options for symptomatic SNs vary, ranging from medical management to surgical fusion. CONCLUSION: SNs are common lesions that are often asymptomatic. In certain cases, SNs can cause back pain. No consensus on pathogenesis exists. There is no established treatment modality for symptomatic SNs.