Tian Wang1, Matthew H Pelletier1, Chris Christou1, Rema Oliver1, Ralph J Mobbs2, William R Walsh3. 1. Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Gate 6, Avoca St, Randwick, Sydney, NSW 2031, Australia. 2. Neurospine Clinic, Prince of Wales Hospital, University of New South Wales, Barker St, Randwick, Sydney, NSW 2031, Australia. 3. Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Gate 6, Avoca St, Randwick, Sydney, NSW 2031, Australia. Electronic address: w.walsh@unsw.edu.au.
Abstract
BACKGROUND CONTEXT: Degenerative disc disease (DDD) is a common, widespread socioeconomic problem. Appropriate large animal models of DDD are required for improved understanding and to serve as preclinical test beds for therapeutic strategies. PURPOSE: To evaluate the effects of short and medium duration immobilization on the sheep lumbar intervertebral disc (IVD) and facet joints (FJs), and to establish a large animal model for DDD research. STUDY DESIGN: An in vivo sheep model evaluating the effect of short- and medium-term immobilization on disc degeneration. METHODS: Eighteen sheep were equally randomized into three groups: short-term (6-week) immobilization (n=6), medium-term (26-week) immobilization (n=6), and control (no surgery) (n=6). Immobilization of L3-L4 was achieved with pedicle screw and rod implantation, the IVD was kept intact, and the annulus and end plates were not disrupted. The IVD and FJs were assessed with planar radiography, computerized tomography (CT), magnetic resonance imaging (MRI), pure moment biomechanical testing, and histologic analysis. RESULTS: Disc height was reduced for 6- and 26-week immobilization groups. The MRI and histologic analysis demonstrated significant disc degeneration for both immobilized groups compared with control, but no statistical difference was detected between short- and medium-term duration. Progressive degenerative changes in FJs were observed with micro-CT and histologic end points. Immobilization significantly reduced lateral bending and flexion-extension range of motion. CONCLUSIONS: The mechanical environment set up by immobilization alone is capable of inducing lumbar disc degeneration at both 6 and 26 weeks in sheep. Longer duration immobilization did not advance disc degeneration process beyond of that found with short duration. The present model produces a degenerative disc with intact annulus and without acute injury, more closely representing the scenario common in human disc degeneration. This provides a suitable large animal in vivo model for the evaluation of the new therapies for disc degeneration. Further studies would do well to examine the effect of remobilization after immobilization in this model.
BACKGROUND CONTEXT: Degenerative disc disease (DDD) is a common, widespread socioeconomic problem. Appropriate large animal models of DDD are required for improved understanding and to serve as preclinical test beds for therapeutic strategies. PURPOSE: To evaluate the effects of short and medium duration immobilization on the sheep lumbar intervertebral disc (IVD) and facet joints (FJs), and to establish a large animal model for DDD research. STUDY DESIGN: An in vivo sheep model evaluating the effect of short- and medium-term immobilization on disc degeneration. METHODS: Eighteen sheep were equally randomized into three groups: short-term (6-week) immobilization (n=6), medium-term (26-week) immobilization (n=6), and control (no surgery) (n=6). Immobilization of L3-L4 was achieved with pedicle screw and rod implantation, the IVD was kept intact, and the annulus and end plates were not disrupted. The IVD and FJs were assessed with planar radiography, computerized tomography (CT), magnetic resonance imaging (MRI), pure moment biomechanical testing, and histologic analysis. RESULTS: Disc height was reduced for 6- and 26-week immobilization groups. The MRI and histologic analysis demonstrated significant disc degeneration for both immobilized groups compared with control, but no statistical difference was detected between short- and medium-term duration. Progressive degenerative changes in FJs were observed with micro-CT and histologic end points. Immobilization significantly reduced lateral bending and flexion-extension range of motion. CONCLUSIONS: The mechanical environment set up by immobilization alone is capable of inducing lumbar disc degeneration at both 6 and 26 weeks in sheep. Longer duration immobilization did not advance disc degeneration process beyond of that found with short duration. The present model produces a degenerative disc with intact annulus and without acute injury, more closely representing the scenario common in humandisc degeneration. This provides a suitable large animal in vivo model for the evaluation of the new therapies for disc degeneration. Further studies would do well to examine the effect of remobilization after immobilization in this model.