Longitudinal characterization of intervertebral disc remodeling following acute annular injury in a rat model of degenerative disc disease.

Objective: Characterize 3D remodeling of the rat intervertebral disc (IVD) following acute annular injury via in vivo micro-computed tomography (µCT), ex vivo contrast-enhanced (CE)-µCT, and histology. Design: Female Lewis rats (N = 4/group) underwent either sham surgery or anterior annular puncture to L3-L4 and L5-L6 (n = 8 IVDs/group) to induce IVD degeneration. Rats were allowed ad libidum cage activity before and after surgery and underwent in vivo µCT scanning at baseline and every 2 weeks post-op for 12 weeks to characterize longitudinal changes in IVD height. At 12 weeks, lumbar spines were dissected and underwent CE-µCT scanning to characterize endpoint glycosaminoglycan distribution and nucleus pulposus (NP) volume ratio. Spines were processed for safranin-O-stained sagittal histology, and IVD degeneration was graded via the Rutges scale. Results: Puncture IVDs exhibited loss of IVD height at all time points from 4 weeks onward compared to Sham-the most severe height loss occurred posteriorly, with significant changes also occurring in the NP and laterally. Puncture IVDs exhibited higher CE-µCT attenuation, indicative of lower glycosaminoglycan content, and reduced NP volume ratio compared to Sham. Histologically, Puncture IVDs had higher Rutges damage scores and exhibited reduced NP cellularity and hydration, disorganized annulus fibrosus (AF) lamellae with evidence of the stab tract, and indistinct AF-NP border compared to Sham. Conclusions: Characterization of the complex, 3D alterations involved in the onset and early progression of IVD degeneration can foster greater understanding of the pathoetiology of IVD degeneration and may inform future studies assessing more sensitive diagnostic techniques or novel therapies.

Dynamic adaptation of vertebral endplate and trabecular bone following annular injury in a rat model of degenerative disc disease.

BACKGROUND CONTEXT: Degenerative disc disease (DDD) is associated with longitudinal remodeling of paravertebral tissues. Although chronic vertebral changes in advanced stages of DDD are well-studied, very little data exists on acute vertebral bone remodeling at the onset and progression of DDD. PURPOSE: To longitudinally characterize bony remodeling in a rodent model of disc injury-induced DDD. STUDY DESIGN: In vivo animal study involving a rat annulus fibrosus injury model of DDD. METHODS: Eight female Lewis rats were assigned to intervertebral disc (IVD) injury (Puncture) or sham surgery (Sham). All rats underwent anterior, transperitoneal approach to the lumbar spine, and Puncture rats underwent annulus fibrosus injury at the L3-L4 and L5-L6 IVDs (n = 8 per group). Live micro computed tomography imaging (10-µm voxel size) was performed 1 week before surgery and postoperatively at 2-week intervals up to a 12-week endpoint. Bone morphology and densitometry of the cranial vertebral body and bony endplate were analyzed and reported with respect to the preoperative baseline scan. Sagittal Safranin-O/Fast-Green and Toluidine Blue histology evaluated using the Rutges IVD score and a custom vertebral endplate score. RESULTS: Vertebral trabecular tissue mineral density (TMD), vertebral trabecular spacing, endplate TMD, and endplate apparent bone mineral density were all significantly greater in Puncture compared with Sham at 4 weeks and each subsequent timepoint. Puncture rats exhibited marginally lower endplate total volume. Anterior endplate osteophyte formation and central physeal ossification were observed in Puncture rats. Endpoint histological analysis demonstrated moderate evidence of IVD degeneration, indicating that vertebral bone adaptation occurs in the acute phases of DDD onset and progression. CONCLUSIONS: Annulus injury-induced DDD leads to acute and progressive changes to the morphology and densitometry of bone in the adjacent vertebral bodies and endplates.