Quantifying a novel three-dimensional marker of scoliosis.

BACKGROUND: Scoliosis causes abnormal spinal curvature and torsional rotation of the vertebrae and has implications for human suffering and societal cost. In differential geometry, Writhe describes three-dimensional curvature. Differential geometric quantities can inform better diagnostic metrics of scoliotic deformity. This evaluation could help physicians and researchers study scoliosis and determine treatments. METHODS: Eight adult lumbar spine CT scans were analyzed in custom MATLAB programs to estimate Writhe and Cobb angle. Five patients exhibited scoliotic curvature, and three controls were asymptomatic. Vertebral centroids in three-dimensional space were determined, and Writhe was approximated. A T-test determined whether the affected spines had greater Writhe than the controls. Cohen's D test was used to determine effect size. RESULTS: Writhe of scoliotic spines (5.4E-4 ± 2.7E-4) was significantly higher than non-scoliotic spines (8.2E-5 ± 1.1E-4; p = 0.008). CONCLUSION: Writhe, a measure of curvature derived from 3D imaging, is significantly greater in scoliotic than in non-scoliotic spines. Future directions must include more subjects and examine writhe as a marker of scoliosis severity, progression, and response to treatment.

Effects of lithium administration on vertebral bone disease in mucopolysaccharidosis I dogs.

Mucopolysaccharidosis (MPS) I is a lysosomal storage disease characterized by deficient activity of the enzyme alpha-L-iduronidase, leading to abnormal accumulation of heparan and dermatan sulfate glycosaminoglycans in cells and tissues. Patients commonly exhibit progressive skeletal abnormalities, in part due to failures of endochondral ossification during postnatal growth. Previously, using the naturally-occurring canine model, we showed that bone and cartilage cells in MPS I exhibit elevated lysosomal storage from an early age and that animals subsequently exhibit significantly diminished vertebral trabecular bone formation. Wnts are critical regulators of endochondral ossification that depend on glycosaminoglycans for signaling. The objective of this study was to examine whether lithium, a glycogen synthase kinase-3 inhibitor and stimulator of Wnt/beta-catenin signaling, administered during postnatal growth could attenuate progression of vertebral trabecular bone disease in MPS I. MPS I dogs were treated orally with therapeutic levels of lithium carbonate from 14 days to 6 months-of-age. Untreated heterozygous and MPS I dogs served as controls. Serum was collected at 3 and 6 months for assessment of bone turnover markers. At the study end point, thoracic vertebrae were excised and assessed using microcomputed tomography and histology. Lithium-treated animals exhibited significantly improved trabecular spacing, number and connectivity density, and serum bone-specific alkaline phosphatase levels compared to untreated animals. Growth plates from lithium-treated animals exhibited increased numbers of hypertrophic chondrocytes relative to both untreated MPS I and heterozygous animals. These findings suggest that bone and cartilage cells in MPS I are still capable of responding to exogenous osteogenic signals even in the presence of significant lysosomal storage, and that targeted osteogenic therapies may represent a promising approach for attenuating bone disease progression in MPS I.

Progression of vertebral bone disease in mucopolysaccharidosis VII dogs from birth to skeletal maturity.

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient ß-glucuronidase activity, leading to accumulation of incompletely degraded heparan, dermatan and chondroitin sulfate glycosaminoglycans. Patients with MPS VII exhibit progressive spinal deformity, which decreases quality of life. Previously, we demonstrated that MPS VII dogs exhibit impaired initiation of secondary ossification in the vertebrae and long bones. The objective of this study was to build on these findings and comprehensively characterize how vertebral bone disease manifests progressively in MPS VII dogs throughout postnatal growth. Vertebrae were collected postmortem from MPS VII and healthy control dogs at seven ages ranging from 9 to 365 days. Microcomputed tomography and histology were used to characterize bone properties in primary and secondary ossification centers. Serum was analyzed for bone turnover biomarkers. Results demonstrated that not only was secondary ossification delayed in MPS VII vertebrae, but that it progressed aberrantly and was markedly diminished even at 365 days-of-age. Within primary ossification centers, bone volume fraction and bone mineral density were significantly lower in MPS VII at 180 and 365 days-of-age. MPS VII growth plates exhibited significantly lower proliferative and hypertrophic zone cellularity at 90 days-of-age, while serum bone-specific alkaline phosphatase (BAP) was significantly lower in MPS VII dogs at 180 days-of-age. Overall, these findings establish that vertebral bone formation is significantly diminished in MPS VII dogs in both primary and secondary ossification centers during postnatal growth.

Global 3D parameter of the spine: application of Calugareanu-White-Fuller theorem in classification of pediatric spinal deformity.

Several classification systems of the spinal curves in adolescent idiopathic scoliosis (AIS) have been developed to guide surgical decision-making. The current classification systems are based on the spinal deformity patterns or deformity magnitudes in one or two anatomical planes. Considering the 3D nature of the spinal deformity in AIS, these classifications fail to capture the spine's curve in its entirety. We proposed a classification based on the axial plane and showed that mathematical analysis of the 3D spinal curve, using differential geometry, supports the differences between the subtypes in this classification system. We calculated the writhe and twist of the entire spinal centerline, elements of the Calugareanu-White-Fuller theorem, in a cohort of 30 right thoracic AIS patients. We also classified this cohort manually based on the vertebral level at which the direction of vertebral rotation caudal to the thoracic curve changes: Lumbar in Group I (V-shaped axial projection) or thoracolumbar in Group II (S-shaped axial projection). The writhe and twist of the spinal curve were significantly different between these manual classification subgroups. Our manual classification distinguished the axial subgroups of right thoracic AIS supported by mathematical specifications of the entire curve in three dimensions. Graphical abstract.

Quantitative MRI correlates with histological grade in a percutaneous needle injury mouse model of disc degeneration.

Low back pain due to disc degeneration is a major cause of morbidity and health care expenditures worldwide. While stem cell-based therapies hold promise for disc regeneration, there is an urgent need to develop improved in vivo animal models to further develop and validate these potential treatments. The objectives of this study were to characterize a percutaneous needle injury model of intervertebral disc degeneration in the mouse caudal spine, and compare two non-invasive quantitative imaging techniques, microcomputed tomography and magnetic resonance imaging (MRI), as effective measures of disc degeneration in this model. Percutaneous needle injury of mouse caudal discs was undertaken using different needle sizes and injury types (unilateral or bilateral annulus fibrosus (AF) puncture). Mice were euthanized 4 weeks post-injury, and MRI and microcomputed tomography were used to determine T2 relaxation time of the NP and disc height index, respectively. Disc condition was then further assessed using semi-quantitative histological grading. Bilateral AF puncture with either 27 or 29G needles resulted in significantly lower T2 relaxation times compared to uninjured controls, while disc height index was not significantly affected by any injury type. There was a strong, inverse linear relationship between histological grade and NP T2 relaxation time. In this study, we demonstrated that quantitative MRI can detect disc degeneration in the mouse caudal spine 4 weeks following percutaneous needle injury, and may therefore serve as a surrogate for histology in longitudinal studies of both disc degeneration and cell-based therapies for disc regeneration using this model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2771-2779, 2018.