Asymmetric Load Transmission Induces Facet Joint Subchondral Sclerosis and Hypertrophy in Patients with Idiopathic Adolescent Scoliosis: Evaluation Using Finite Element Model and Surgical Specimen.

Adolescent idiopathic scoliosis (AIS) with thoracic curvature primarily progresses from the thoracolumbar region, causing abnormal twisting and rotation of the spinal column. This results in unbalanced, asymmetric loads on each vertebrae and increased demands on the thoracic facet joints to withstand rotational stress from adjacent vertebrae. However, no studies have focused on the stress distribution on the facet joints of the thoracic spine in patients with AIS. This study aimed to investigate the mechanical loading and its distribution on the thoracic facet joints of AIS patients using finite element (FE) analysis and surgical specimens. FE models of the thoracic spine were created from a total of 13 female AIS patients (Lenke type 1, n = 4; Lenke type 2, n = 4; Lenke type 3, n = 5). A load of 200 N on the T3 vertebrae and 30 N each on the bilateral superior articular processes were applied vertically to quantify the contact force on the facet joints from T3 to T11. In addition, morphological and histological analyses were performed on the inferior articular processes obtained during surgery. FE analysis demonstrated that contact forces of the facet joint progressively increased from the mid to lower thoracic spine of the concave side, reaching a maximum around the apex. More than 91% of the load was transmitted by the facet joints at the concave side, resulting in facet joint subchondral sclerosis and hypertrophy. The apical facet joint in AIS helps counteract rotational stress between vertebrae and transfers most stress through the concave side. In conclusion, this study found that asymmetric load transfer in the facet joints leads to subchondral sclerosis and hypertrophy. These findings can enhance our understanding of the stress loading on facet joints and the resulting biological changes and help clarify the mechanisms involved in scoliosis progression. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Rod Rotation with Outrigger Is Substantial for Correcting Apical Hypokyphosis in Patients with Adolescent Idiopathic Scoliosis: Novel Outrigger Device for Concave Rod Rotation.

The apical hypokyphosis of scoliotic patients is thought to lead to decreased lung capacity and cause shortness of breath. Additionally, concave rod curve reduction is a problem in the correction of apical hypokyphosis in posterior spinal fusion surgery in adolescent idiopathic scoliosis (AIS). We investigated the contributions of rod rotation (RR) with an outrigger device, followed by differential rod contouring (DRC) with the outrigger attached to the concave rod, designed to prevent concave rod curve-flattening. We analyzed and compared the results of segmental pedicle screw fixation without the outrigger in 41 AIS patients with thoracic curves (Lenke type I, 25; type II, 16) to those corrected using the outrigger in 36 patients (Lenke type I, 24; type II,12). The changes in the Cobb angle, apical kyphosis of five vertebrae, thoracic kyphosis (TK, T4-12), correction rate, correction angle of apical vertebral rotation, spinal penetration index (SPi), and rib hump index (RHi) before and after surgery were measured, and the contribution of the outrigger was analyzed. The mean scoliosis correction rates without and with the outrigger were 72.1° and 75.6°, respectively (p = 0.03). Kyphosis of the five apical vertebrae and TK were significantly greater in the surgery with the outrigger (p = 0.002). Significantly greater improvements in SPi and RHi were also noted in the surgery with the outrigger (p < 0.05). The use of concave RR and convex DRC with the outrigger appear to be advantageous for correcting apical hypokyphosis, followed by the subsequent formation of TK. As a result, breathing problems are less likely to occur during daily life because of improvements in SPi and RHi.

The origins and roles of osteoclasts in bone development, homeostasis and repair.

The mechanisms underlying bone development, repair and regeneration are reliant on the interplay and communication between osteoclasts and other surrounding cells. Osteoclasts are multinucleated monocyte lineage cells with resorptive abilities, forming the bone marrow cavity during development. This marrow cavity, essential to hematopoiesis and osteoclast-osteoblast interactions, provides a setting to investigate the origin of osteoclasts and their multi-faceted roles. This Review examines recent developments in the embryonic understanding of osteoclast origin, as well as interactions within the immune environment to regulate normal and pathological bone development, homeostasis and repair.

Efficacy of surgeon-directed postoperative local injection with an analgesic mixture in posterior fusion surgery for adolescent idiopathic scoliosis.

BACKGROUND: Severe postsurgical pain in posterior spinal fusion is common. Multimodality analgesia, including opioid-based patient-controlled analgesia (PCA), is commonly used, but opioid-related adverse events such as nausea and vomiting are sometimes a problem. We used a ropivacaine-epinephrine-dexamethasone mixture given as one-time local bilateral submyofascial injections at the operated levels added to conventional multimodality analgesia including PCA for postoperative pain control in one group of patients to confirm whether administration of this mixture reduced postoperative pain and opioid use status post posterior spinal fusion. METHODS: We retrospectively reviewed 67 consecutive patients who had undergone posterior fusion surgery for adolescent idiopathic scoliosis (AIS), 35 of whom were treated with conventional analgesia that consisted mainly of PCA (control group) and 32 of whom were treated with one-time submyofascial injections of a ropivacaine-epinephrine-dexamethasone mixture (submyofascial injection group) added to conventional multimodality analgesia. We compared postsurgical pain levels and the amount of opioid use over the first 48 h after surgery, as well as physical activity levels and adverse events 2 weeks after surgery. RESULTS: Postsurgical pain quantified by a numeric rating scale (1-10) in the submyofascial injection group was significantly lower than that in the control group. The amount of fentanyl use was significantly less in the submyofascial injection group at 24 h, 48 h, and all subsequent periods after surgery. In addition, Walking Recovery Time (WRT) defined as the number of days until the first event of ambulation was significantly less in the submyofascial injection group (3.3 d vs 4.1 d, P = 0.0007)). Laxative use was significantly less in the submyofascial injection group (0.3 times vs 1.3 times, P = 0.02). CONCLUSIONS: One-time submyofascial injections at the operated levels with a ropivacaine-epinephrine-dexamethasone mixture after spinal fusion surgery reduced pain, opioid consumption, and opioid-related adverse events. This technique can contribute significantly to postoperative analgesia.

Distinct Roles of Glutamine Metabolism in Benign and Malignant Cartilage Tumors With IDH Mutations.

Enchondromas and chondrosarcomas are common cartilage neoplasms that are either benign or malignant, respectively. The majority of these tumors harbor mutations in either IDH1 or IDH2. Glutamine metabolism has been implicated as a critical regulator of tumors with IDH mutations. Using genetic and pharmacological approaches, we demonstrated that glutaminase-mediated glutamine metabolism played distinct roles in enchondromas and chondrosarcomas with IDH1 or IDH2 mutations. Glutamine affected cell differentiation and viability in these tumors differently through different downstream metabolites. During murine enchondroma-like lesion development, glutamine-derived α-ketoglutarate promoted hypertrophic chondrocyte differentiation and regulated chondrocyte proliferation. Deletion of glutaminase in chondrocytes with Idh1 mutation increased the number and size of enchondroma-like lesions. In contrast, pharmacological inhibition of glutaminase in chondrosarcoma xenografts reduced overall tumor burden partially because glutamine-derived non-essential amino acids played an important role in preventing cell apoptosis. This study demonstrates that glutamine metabolism plays different roles in tumor initiation and cancer maintenance. Supplementation of α-ketoglutarate and inhibiting GLS may provide a therapeutic approach to suppress enchondroma and chondrosarcoma tumor growth, respectively. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Tumor-propagating side population cells are a dynamic subpopulation in undifferentiated pleomorphic sarcoma.

Sarcomas contain a subpopulation of tumor-propagating cells (TPCs) with enhanced tumor-initiating and self-renewal properties. However, it is unclear whether the TPC phenotype in sarcomas is stable or a dynamic cell state that can derive from non-TPCs. In this study, we utilized a mouse model of undifferentiated pleomorphic sarcoma (UPS) to trace the lineage relationship between sarcoma side population (SP) cells that are enriched for TPCs and non-SP cells. By cotransplanting SP and non-SP cells expressing different endogenous fluorescent reporters, we show that non-SP cells can give rise to SP cells with enhanced tumor-propagating potential in vivo. Lineage trajectory analysis using single-cell RNA sequencing from SP and non-SP cells supports the notion that non-SP cells can assume the SP cell phenotype de novo. To test the effect of eradicating SP cells on tumor growth and self-renewal, we generated mouse sarcomas in which the diphtheria toxin receptor is expressed in the SP cells and their progeny. Ablation of the SP population using diphtheria toxin did not impede tumor growth or self-renewal. Altogether, we show that the sarcoma SP represent a dynamic cell state and targeting TPCs alone is insufficient to eliminate tumor progression.

Monocyte/Macrophage Lineage Cells From Fetal Erythromyeloid Progenitors Orchestrate Bone Remodeling and Repair.

A third of the population sustains a bone fracture, and the pace of fracture healing slows with age. The slower pace of repair is responsible for the increased morbidity in older individuals who sustain a fracture. Bone healing progresses through overlapping phases, initiated by cells of the monocyte/macrophage lineage. The repair process ends with remodeling. This last phase is controlled by osteoclasts, which are bone-specific multinucleated cells also of the monocyte/macrophage lineage. The slower rate of healing in aging can be rejuvenated by macrophages from young animals, and secreted proteins from macrophage regulate undifferentiated mesenchymal cells to become bone-forming osteoblasts. Macrophages can derive from fetal erythromyeloid progenitors or from adult hematopoietic progenitors. Recent studies show that fetal erythromyeloid progenitors are responsible for the osteoclasts that form the space in bone for hematopoiesis and the fetal osteoclast precursors reside in the spleen postnatally, traveling through the blood to participate in fracture repair. Differences in secreted proteins between macrophages from old and young animals regulate the efficiency of osteoblast differentiation from undifferentiated mesenchymal precursor cells. Interestingly, during the remodeling phase osteoclasts can form from the fusion between monocyte/macrophage lineage cells from the fetal and postnatal precursor populations. Data from single cell RNA sequencing identifies specific markers for populations derived from the different precursor populations, a finding that can be used in future studies. Here, we review the diversity of macrophages and osteoclasts, and discuss recent finding about their developmental origin and functions, which provides novel insights into their roles in bone homeostasis and repair.

Yolk-sac-derived macrophages progressively expand in the mouse kidney with age.

Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, angiogenesis, and tissue remodeling. Recent reports highlight differential roles for ontogenically distinct renal macrophage populations in disease. However, little is known about how these populations change over time in normal, uninjured kidneys. Prior reports demonstrated a high proportion of HSC-derived macrophages in the young adult kidney. Unexpectedly, using genetic fate-mapping and parabiosis studies, we found that yolk-sac-derived macrophages progressively expand in number with age and become a major contributor to the renal macrophage population in older mice. This chronological shift in macrophage composition involves local cellular proliferation and recruitment from circulating progenitors and may contribute to the distinct immune responses, limited reparative capacity, and increased disease susceptibility of kidneys in the elderly population.

Older people are more likely to develop kidney disease, which increases their risk of having other conditions such as a heart attack or stroke and, in some cases, can lead to their death. Older kidneys are less able to repair themselves after an injury, which may help explain why aging contributes to kidney disease. Another possibility is that older kidneys are more susceptible to excessive inflammation. Learning more about the processes that lead to kidney inflammation in older people might lead to better ways to prevent or treat their kidney disease. Immune cells called macrophages help protect the body from injury and disease. They do this by triggering inflammation, which aides healing. Too much inflammation can be harmful though, making macrophages a prime suspect in age-related kidney harm. Studying these immune cells in the kidney and how they change over the lifespan could help scientists to better understand age-related kidney disease. Now, Ide, Yahara et al. show that one type of macrophage is better at multiplying in older kidneys. In the experiments, mice were genetically engineered to make a fluorescent red protein in one kind of macrophage. This allowed Ide, Yahara et al. to track these immune cells as the mice aged. The experiments showed that this subgroup of cells is first produced when the mice are embryos. They stay in the mouse kidneys into adulthood, and are so prolific that, over time, they eventually become the most common macrophage in older kidneys. The fact that one type of embryonically derived macrophage takes over with age may explain the increased inflammation and reduced repair capacity seen in aging kidneys. More studies will help scientists to understand how these particular cells contribute to age-related changes in susceptibility to kidney disease.

Sacroiliac joint variation associated with diffuse idiopathic skeletal hyperostosis.

BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by the ossification of vertebral bodies and peripheral entheses. However, variations in sacroiliac (SI) joint change in patients with DISH have not been fully clarified. The purpose of this study was to evaluate SI joint variation in patients with DISH in comparison with a non-DISH population. METHODS: A total of 342 SI joints in 171 patients (DISH+, n = 86; DISH-, n = 85) who had undergone lumbar spine surgery were analyzed by computed tomography examination. SI joint variations were classified into four types: Type 1, normal or tiny peripheral bone irregularity; Type 2, subchondral bone sclerosis and osteophytes formation; Type 3, vacuum phenomenon; and Type 4, bridging osteophyte and bony fusion. The type of bridging osteophyte in SI joints and the prevalence of ossification in each spinal segment from C1 to SI joint were also examined. RESULTS: The most common SI joint variation in the DISH+ group was bony fusion (Type 4), with 71.6% exhibiting anterior paraarticular bridging. On the other hand, SI joint vacuum phenomenon (Type 3) was the most frequent change (57.1%) in the DISH- group. The middle to lower thoracic spine and SI joints were highly affected in DISH and caused bony ankylosis. CONCLUSIONS: Anterior paraarticular bridging was the most common type of SI joint change in patients with DISH who underwent lumbar spine surgery. The present results regarding variations of SI joint changes in DISH should help understand the etiology of DISH.

Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair.

Osteoclasts are multinucleated cells of the monocyte/macrophage lineage that degrade bone. Here, we used lineage tracing studies-labelling cells expressing Cx3cr1, Csf1r or Flt3-to identify the precursors of osteoclasts in mice. We identified an erythromyeloid progenitor (EMP)-derived osteoclast precursor population. Yolk-sac macrophages of EMP origin produced neonatal osteoclasts that can create a space for postnatal bone marrow haematopoiesis. Furthermore, EMPs gave rise to long-lasting osteoclast precursors that contributed to postnatal bone remodelling in both physiological and pathological settings. Our single-cell RNA-sequencing data showed that EMP-derived osteoclast precursors arose independently of the haematopoietic stem cell (HSC) lineage and the data from fate tracking of EMP and HSC lineages indicated the possibility of cell-cell fusion between these two lineages. Cx3cr1+ yolk-sac macrophage descendants resided in the adult spleen, and parabiosis experiments showed that these cells migrated through the bloodstream to the remodelled bone after injury.

Three-Dimensional Computed Tomography Analysis of Spinal Canal Length Increase After Surgery for Adolescent Idiopathic Scoliosis: A Multicenter Study.

BACKGROUND: The most severe complication after surgery for adolescent idiopathic scoliosis is spinal cord injury. There is a relationship between corrective surgery and subsequent elongation of the spinal canal. We sought to investigate which factors are involved in this phenomenon. METHODS: Seventy-seven patients with adolescent idiopathic scoliosis (49 with Lenke type 1 and 28 with type 2) who underwent spinal correction surgery were included. The mean patient age at surgery was 14.2 years (range, 11 to 20 years). The spines of all patients were fused within the range of T2 to L2, and computed tomography (CT) data were retrospectively collected. We measured the preoperative and postoperative lengths of the spinal canal from T2 to L2 using 3-dimensional (3D) CT-based imaging software. We also examined the association between the change in T2-L2 spinal canal length and the radiographic parameters. RESULTS: The length of the spinal canal from T2 to L2 was increased by a mean of 8.5 mm in the patients with Lenke type 1, 12.7 mm in those with type 2, and 10.1 mm overall. Elongation was positively associated with the preoperative main thoracic Cobb angle in both the type-1 group (R = 0.43, p < 0.005) and the type-2 group (R = 0.77, p < 0.000001). The greatest elongation was observed in the periapical vertebral levels of the main thoracic curves. CONCLUSIONS: Corrective surgery for adolescent idiopathic scoliosis elongated the spinal canal. The preoperative proximal, main thoracic, and thoracolumbar/lumbar Cobb angles are moderate predictors of postoperative spinal canal length after scoliosis surgery. CLINICAL RELEVANCE: It is important to understand how much the spinal canal is elongated after surgery to lessen the risk of intraoperative and postoperative neurological complications.

Differential rod contouring on thoracolumbar/lumbar curvature in patients with adolescent idiopathic scoliosis: An analysis with intraoperative acquisition of three-dimensional imaging.

BACKGROUND: Differential rod contouring (DRC) is useful for periapical vertebral derotation and decreasing rib hump in patients with thoracic adolescent idiopathic scoliosis (AIS). However, it is unknown whether DRC in the thoracolumbar/lumbar spine also contributes to derotation. We assessed the contributions of rod contouring and of DRC to the reduction of apical axial vertebral body rotation in patients with AIS with thoracolumbar/lumbar curvatures. METHODS: Forty-five (Lenke type 3 or 4, 17; Lenke type 5 or 6, 28) were analyzed for the contribution of DRC to thoracolumbar/lumbar spinal derotation. Rod contouring was assessed by comparing the preinsertion x-ray with the post-operative CT images. Intraoperative C-arm fluoroscopic scans of the periapical vertebrae of the thoracolumbar/lumbar curve of the scoliosis (135 vertebrae) were taken post-rod rotation (RR) and post-DRC in all patients. Three-dimensional images were automatically reconstructed from the taken x-ray images. The angle of vertebral body rotation in these apical vertebrae was measured, and the contribution of DRC to apical vertebral body derotation and rib hump index (RHi) for lumbar prominence was analyzed. RESULTS: The pre-implantation convex rod curvatures of both Lenke 3/4 and 5/6 groups decreased after surgery. The mean further reductions in vertebral rotation with post-RR DRC were 3.7° for Lenke 3/4 and 4.4° for Lenke 5/6 (P < 0.01). Both changes in apical vertebral rotation and in RHi for evaluating lumbar prominence were significantly correlated with the difference between concave and convex rod curvature in preimplantation. Vertebral derotation was significantly higher in curves with a difference >20° (P < 0.05). CONCLUSIONS: DRC following rod rotation contributed substantial additional benefit to reducing vertebral rotation and decreasing lumbar prominence in thoracolumbar/lumbar scoliosis.

The effect of multiple lesions in patients with ossification of the posterior longitudinal ligament of the cervical spine.

PURPOSE: Ossification of the posterior longitudinal ligament of the cervical spine (cervical OPLL) is associated with the lesions at the thoracic and/or lumbar spine. Multiple spinal lesions cause additional neurological deficit, affecting the outcomes of cervical laminoplasty. This study aimed to clarify the effect of multiple lesions on the outcomes of cervical laminoplasty and to compare the results with data from patients without them. METHODS: From April 1981 to October 2015, 201 patients underwent laminoplasty for cervical OPLL; however, 167 patients were followed for >2 years. Twenty-four patients underwent additional surgery for multiple lesions due to spinal stenosis. The pathologies of the lesions were assessed. The patients were divided into two groups: the thoracic and thoraco-lumbar group (T-group: 8 patients) and the lumbar group (L-group: 16 patients). One-hundred patients without an additional surgery served as the control group. The maximum Japanese Orthopaedic Association (JOA) score and the most recent score for recovery was compared between the multiple and control groups. RESULTS: The maximum score and recovery rate and the score and recovery rate at the last follow-up in the multiple group were lower than those in the control group. There was no significant difference in the postoperative JOA score and recovery rate between the T-group and the L-group. CONCLUSIONS: Neurological recovery in patients with multiple lesions was poorer than in those without lesions. Therefore, special attention should be paid to cervical OPLL with multiple spinal lesions.

Clinical Impact of Ossification of the Posterior Longitudinal Ligament Progression After Cervical Laminoplasty.

STUDY DESIGN: This is a retrospective study. OBJECTIVES: (1) To analyze the incidence of second surgery after initial laminoplasty for ossification of the posterior longitudinal ligament (OPLL) due to disease progression, (2) to examine factors associated with poor surgical outcome. SUMMARY OF BACKGROUND DATA: Neurological deterioration after laminoplasty is frequently encountered due to OPLL progression. PATIENTS AND METHODS: Of 201 OPLL patients treated by laminoplasty at a single-institution, the 153 monitored for >3 years postsurgery were included in this analysis. Neurological findings were graded by the Japanese Orthopaedic Association (JOA) score. We retrospectively examined the incidence of second surgery due to OPLL progression. We also evaluated the clinical characteristics and the surgical outcomes after second operation to identify potential risk factors for poor outcome. RESULTS: Eight patients required a second surgery due to OPLL progression. Neurological recovery was achieved in 5 of these patients, whereas 3 exhibited continued dysfunction. Patients with poor recovery showed kyphotic changes of spinal alignment and high-intensity regions in the spinal cord on T2-weighted magnetic resonance images (T2-MRI). CONCLUSIONS: Only a small fraction of OPLL patients required a second surgery due to OPLL progression. Recovery was poor in those with clear high-intensity T2-MRI signals in the spinal cord.

Macrophage cells secrete factors including LRP1 that orchestrate the rejuvenation of bone repair in mice.

The pace of repair declines with age and, while exposure to a young circulation can rejuvenate fracture repair, the cell types and factors responsible for rejuvenation are unknown. Here we report that young macrophage cells produce factors that promote osteoblast differentiation of old bone marrow stromal cells. Heterochronic parabiosis exploiting young mice in which macrophages can be depleted and fractionated bone marrow transplantation experiments show that young macrophages rejuvenate fracture repair, and old macrophage cells slow healing in young mice. Proteomic analysis of the secretomes identify differential proteins secreted between old and young macrophages, such as low-density lipoprotein receptor-related protein 1 (Lrp1). Lrp1 is produced by young cells, and depleting Lrp1 abrogates the ability to rejuvenate fracture repair, while treating old mice with recombinant Lrp1 improves fracture healing. Macrophages and proteins they secrete orchestrate the fracture repair process, and young cells produce proteins that rejuvenate fracture repair in mice.

Sporadic hemangioblastoma of the film terminale with peritumoral cyst.

BACKGROUND: Spinal hemangioblastoma originating from the film terminale are rare tumors. Here, we present a film terminale hemangioblastoma and review the appropriate literature. CASE DESCRIPTION: A 37-year-old female presented with bilateral lower extremity pain without a focal neurological deficit. The magnetic resonance (MR) image demonstrated an intradural spinal tumor at the L1 level, which was accompanied by peritumoral cysts. In addition, there were multiple surpentine flow voids (e.g., consistent with torturous and convoluted vessels), which is typical for hemangioblastoma. At surgery, a spinal hemangioblastoma originating from the film terminale with peritumoral cysts at the L1 level was fully excised without producing a focal postoperative neurological deficit. Histological examination revealed stromal cells with vacuolated cytoplasm and small nuclei in a rich capillary network accompanied by several enlarged vessels. These finding were compatible with a hemangioblastoma. CONCLUSIONS: We reported a rare case of a hemangioblastoma originating from the conus presenting at the L1 level. Complete surgical resection was accomplished without any motor deficit.

Selection of posterior spinal osteotomies for more effective periapical segmental vertebral derotation in adolescent idiopathic scoliosis-An in vivo comparative analysis between Ponte osteotomy and inferior facetectomy alone.

BACKGROUND: Ponte osteotomy is a useful method in posterior spinal release. However, it is unclear whether Ponte osteotomy itself contributes to vertebral derotation in surgery for adolescent idiopathic scoliosis (AIS) patients compared to inferior facetectomy alone. This study aimed to assess the effect of Ponte osteotomy on the magnitude of periapical vertebral body rotation compared to inferior facetectomy alone. This study was a prospective collected data. METHODS: The study included 63 patients with AIS (Thoracic curve type, 35; thoracolumbar/lumbar curve type, 27), who underwent surgery between August 2011 and January 2015. All AIS patients underwent posterior spinal fusion with uniplanar screws and Ponte osteotomies on three periapical intervertebral segments. We measured and analyzed the flexibility of periapical intervertebral rotation pre- and post-bilateral inferior facetectomy, and post-Ponte osteotomy with our device (three times). The difference in intervertebral rotation between pre- and post-Ponte osteotomy was analyzed. RESULTS: The mean increase in angle was 5.6° for thoracic curves and 6.4° for thoracolumbar curves. The increase in angle for thoracolumbar curves was significantly larger than that for thoracic curves (P < 0.05). The more an apical region of the scoliosis was located at caudal side of spine, the more the flexibility due to Ponte osteotomy increased (P < 0.05). The significant differences of the increase in intervertebral flexibility between inferior facetectomies and Ponte osteotomies were recognized at middle thoracic and thoracolumbar regions (P < 0.005). CONCLUSIONS: Our data suggest that Ponte osteotomy has a loosening effect on periapical scoliotic curvature compared to inferior facetectomy alone. Ponte osteotomy is likely to be associated with an increase in loosening of the middle thoracic and thoracolumbar regions.

Lumbar spine surgery in patients with rheumatoid arthritis (RA): what affects the outcomes?

BACKGROUND CONTEXT: Although the cervical spine is only occasionally involved in rheumatoid arthritis (RA), involvement of the lumbar spine is even less common. A few reports on lumbar spinal stenosis in patients with RA have appeared. Although disc space narrowing occurs in aging, postoperative adjacent segment disease (ASD) in patients with RA has not been subject to much analysis. PURPOSE: The objective of this study was to investigate differences in ASD and clinical outcomes between lumbar spinal decompression with and without fusion in patients with RA. STUDY DESIGN/SETTING: This is a retrospective comparative study. PATIENT SAMPLE: A total of 52 patients with RA who underwent surgery for lumbar spinal disorders were included. Twenty-seven patients underwent decompression surgery with fusion and 25 underwent decompression surgery alone. OUTCOME MEASURES: Intervertebral disc space narrowing and spondylolisthesis of the segment immediately cranial to the surgical site were measured using a three-dimensional volume rendering software. Pre- and postoperative evaluation of RA activity and Japanese Orthopaedic Association (JOA) scores were conducted. MATERIALS AND METHODS: All patients had preoperative and annual postoperative lumbar radiographs and were followed up for a mean of 5.1 years (range 3.5-10.9 years). Pre- and postoperative (2 years after surgery) JOA scores were recorded and any postoperative complications were investigated. Degrees of intervertebral disc narrowing and spondylolisthesis at the adjacent levels were evaluated on radiographs and were compared between the two groups. Analysis was performed to look for any correlation between ASD and RA disease activities. RESULTS: Postoperative JOA scores were significantly improved in both groups. The rate of revision surgery was significantly higher in the fusion group than that in the non-fusion group. The rate of ASD was significantly greater in the fusion group than that in the non-fusion group at the final follow-up examination. Both matrix metalloproteinase 3 (MMP-3) and the 28-joint disease activity score incorporating C-reactive protein levels (DAS28-CRP) were significantly associated with the incidence and severity of ASD. CONCLUSIONS: Adjacent segment disease and the need for revision surgery were significantly higher in the fusion group than those in the non-fusion group. A preoperative high MMP-3 and DAS28-CRP are likely to be associated with postoperative ASD.

Sternum-splitting anterior approach following posterior decompression and fusion in patients with massive ossification of the posterior longitudinal ligament in the upper thoracic spine: report of 2 cases and literature review.

PURPOSE: Anterior approach to the upper thoracic spine is difficult. It is important for spine surgeons to know the indication and the effect of anterior decompression for upper thoracic lesions and also to recognize the complications which are related to the approach with sternotomy. We present two patients for whom we took the sternum-splitting anterior approach for thoracic ossification of the posterior longitudinal ligament (OPLL) following posterior decompression and fusion surgery; the clinical course and surgical outcome are discussed, with particular reference to complication avoidance and also we review the previous literature. METHODS: We present two cases with severe upper thoracic OPLL. The maximum occupying ratio of OPLL against the spinal canal was more than 80% in both cases. Posterior decompression and fusion were not effective and, therefore, anterior surgery with sternotomy was carried out. RESULTS: Cerebrospinal fluid leak was encountered with the removal of OPLL using the anterior approach. Subsequently, a polyglycolic acid sheet was used to cover the defect in the dura matter; a thoracic drainage system with a continuous suction unit was positioned at the surgical wound to avoid fluid retention in the mediastinum. In addition, we facilitated spinal drainage from the lumbar level. These procedures resulted in no complication caused by fluid retention in the mediastinum. CONCLUSION: Both a safe surgical approach and preventive measures to alleviate postoperative complications are mandatory in difficult cases with thoracic OPLL.

A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain.

Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1ß-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.