Lumbar Disc Degeneration Phenotypes

The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University. All the experimental protocol and the methods were carried out in accordance with the relevant guidelines and regulations, and complied with the principles of the Declaration of Helsinki. Written informed consent was achieved from each participant.
This study participant including 454 patients with LDD and 485 controls were recruited from Spine Surgery and Physical Examination Center, the First Affiliated Hospital of Guangxi Medical University. The control group was composed of 252 females and 233 males, and the case group was composed of 259 females and 195 males. All patients were diagnosed with LDD based on clinical examinations and Magnetic Resonance Imaging (MRI). Clinical examinations were performed by one attending spine surgeon. MRI images were obtained using a 1.5-T magnetic resonance imaging Achieva scanner (Philips Medical Systems; Best, the Netherlands) with Nova Dual gradients. The following inclusion criteria were applied: (1) low back pain as the main symptom for at least 3 months; (2) MRI shows degenerative changes in lumbar spine; (3) no previous spinal surgery or other treatment that would deform the lumbar spine. Evaluation of the characteristics of the phenotypes based on MRI was performed by two independent radiologists. Any dispute between the two radiologists was resolved by a senior radiologist. According to MRI phenotypes^{36 (link)}, the patients with LDD were further divided into three different mutually exclusive subgroups based on as follows: subgroup 1 included 266 patients affected by lumbar disc herniation; subgroup 2 included 105 patients affected by lumbar spinal stenosis and subgroup 3 included 83 patients affected by lumbar spondylolisthesis (Fig. 3). The exclusion criteria were applied: (1) a history of clinician-diagnosed low back pain at least six months’ duration that was present more than half the days of the month; (2) spine deformity; (3) the history of intraspinal tumor, trauma, inflammatory disease and rheumatoid arthritis; (4) previous spinal surgery; (5) MRI phenotype of one patient fit into more than one subgroup. To be eligible for control group, the subjects had no history of low back pain, and were screened by a 1.5-T lumbar spine MRI scan. Disc degeneration were identified in the MRI images and graded according to the modified Pfirrmann grading system^{39 (link)}. The subjects with Pfirrmann’s Grade 1 were included in control group. Furthermore, we collected degenerative disc tissues (n = 34) and normal disc tissues (n = 21) from patients with lumbar disc herniation (subgroup 1) and patients with traumatic lumbar vertebral fracture, respectively. Patients with traumatic lumbar fracture had no history of low back pain before surgery and MRI evaluation showed no significant disc degeneration. According to Schneiderman’s classification^{40 (link)}, Grade 1 was in 19 patients and Grade 2 was in 2 patients. These samples were used to evaluate VDR expression via immunohistochemistry (IHC).Figure 3

Classification of patients into subgroups by MRI imaging. (A) Subgroup 1: patients with lumbar disc herniation; white arrow indicates L4/5 herniated disk bulges out toward the spinal canal. (B) Subgroup 2: patients with lumbar spinal stenosis; white arrows indicate L3-4 level spinal stenosis caused by degenerative thickening of the ligamentum flavum. (C) Subgroup 3: patients with lumbar spondylolisthesis; white arrow indicates subluxation of L5 vertebral body relative to S1 vertebral body.