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.

Association between serum interleukin-17 levels and ectopic bone formation in OPLL patients with DISH.

OBJECTIVE: To investigate the relationship between the severity and morphology of heterotopic ossification in the spinal ligaments including sacroiliac (SI) joints, and serum interleukin-17 (IL-17) levels in patients with ossification of the posterior longitudinal ligament (OPLL) with or without diffuse idiopathic skeletal hyperostosis (DISH), as well as a non-OPLL group. METHODS: A total of 103 patients with OPLL (DISH (-), n = 50; DISH (+), n = 53) and 53 age- and gender-matched controls were included. The serum levels of IL-17 were analyzed, and the severity of ectopic ossification and the morphology of ectopic bone formation were evaluated. The SI joint morphological variations were categorized into four types. RESULTS: No significant differences were found in serum IL-17 levels between the OPLL and control groups. However, the DISH (+) group showed higher IL-17 levels than the DISH (-) group, especially in female patients (p = 0.003). Additionally, IL-17 levels were positively correlated with the number of Flat vertebral units, meaning one of the characteristics of DISH ossification type (R2 = 0.199, p = 0.012). IL-17 levels in type 4 were significantly higher in the DISH (+) group than in the DISH (-) group. CONCLUSIONS: The morphological characteristics of paravertebral bone formation in the entire spine, including the SI joint, are likely associated with serum IL-17 levels in OPLL. These findings provide pathological and serological evidence of local inflammation contributing to paravertebral ossification of OPLL patients.

Sacroiliac Joint Variation in Patients With Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: Ossification of the posterior longitudinal ligament (OPLL) reveals heterotopic ossification in the spinal ligament. OPLL also tends to ossify ligaments and entheses throughout the body. However, hallmarks of sacroiliac (SI) joint ossification and its variation in OPLL have not been clarified. Here, we investigated the morphological changes in SI joints in individuals with and without OPLL. METHODS: We included 240 age- and sex-matched patients (OPLL+, 120; OPLL-, 120) in the study. SI joint variations were classified into 4 types: Type 1, normal or small peripheral bone irregularity; Type 2, subchondral bone sclerosis and osteophyte formation; Type 3, vacuum phenomenon; and Type 4, bridging osteophyte and bony fusion. Type 4 was further divided into 3 subgroups as previously described. Interactions between the ossified spinal region in OPLL and morphological changes in the SI joint were evaluated. RESULTS: SI joint ankylosis occurs more frequently in patients with OPLL (51.7%) than in those without (non-OPLL) (33.3%). The SI joint vacuum phenomenon (49.2%) was the main finding in non-OPLL. SI joint ankylosis in OPLL was characterized by anterior bridging and intra-articular fusion. OPLL patients with multilevel ossification tend to develop degeneration and ankylosis of the SI joints. CONCLUSIONS: OPLL conferred a high risk of SI joint ossification compared with non-OPLL, and patients with extensive ossification had a higher rate of SI joint ankylosis. Understanding SI joint variation could help elucidate OPLL etiology and clarify the phenotypic differences in the SI joint between OPLL and other spinal disorders.

A deep convolutional neural network to predict the curve progression of adolescent idiopathic scoliosis: a pilot study.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that predominantly occurs in girls. While skeletal growth and maturation influence the development of AIS, accurate prediction of curve progression remains difficult because the prognosis for deformity differs among individuals. The purpose of this study is to develop a new diagnostic platform using a deep convolutional neural network (DCNN) that can predict the risk of scoliosis progression in patients with AIS. METHODS: Fifty-eight patients with AIS (49 females and 9 males; mean age: 12.5 ± 1.4 years) and a Cobb angle between 10 and 25 degrees (mean angle: 18.7 ± 4.5) were divided into two groups: those whose Cobb angle increased by more than 10 degrees within two years (progression group, 28 patients) and those whose Cobb angle changed by less than 5 degrees (non-progression group, 30 patients). The X-ray images of three regions of interest (ROIs) (lung [ROI1], abdomen [ROI2], and total spine [ROI3]), were used as the source data for learning and prediction. Five spine surgeons also predicted the progression of scoliosis by reading the X-rays in a blinded manner. RESULTS: The prediction performance of the DCNN for AIS curve progression showed an accuracy of 69% and an area under the receiver-operating characteristic curve of 0.70 using ROI3 images, whereas the diagnostic performance of the spine surgeons showed inferior at 47%. Transfer learning with a pretrained DCNN contributed to improved prediction accuracy. CONCLUSION: Our developed method to predict the risk of scoliosis progression in AIS by using a DCNN could be a valuable tool in decision-making for therapeutic interventions for AIS.

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.

Association of Ligamentum Flavum Hypertrophy with Adolescent Idiopathic Scoliosis Progression-Comparative Microarray Gene Expression Analysis.

The role of the ligamentum flavum (LF) in the pathogenesis of adolescent idiopathic scoliosis (AIS) is not well understood. Using magnetic resonance imaging (MRI), we investigated the degrees of LF hypertrophy in 18 patients without scoliosis and on the convex and concave sides of the apex of the curvature in 22 patients with AIS. Next, gene expression was compared among neutral vertebral LF and LF on the convex and concave sides of the apex of the curvature in patients with AIS. Histological and microarray analyses of the LF were compared among neutral vertebrae (control) and the LF on the apex of the curvatures. The mean area of LF in the without scoliosis, apical concave, and convex with scoliosis groups was 10.5, 13.5, and 20.3 mm2, respectively. There were significant differences among the three groups (p < 0.05). Histological analysis showed that the ratio of fibers (Collagen/Elastic) was significantly increased on the convex side compared to the concave side (p < 0.05). Microarray analysis showed that ERC2 and MAFB showed significantly increased gene expression on the convex side compared with those of the concave side and the neutral vertebral LF cells. These genes were significantly associated with increased expression of collagen by LF cells (p < 0.05). LF hypertrophy was identified in scoliosis patients, and the convex side was significantly more hypertrophic than that of the concave side. ERC2 and MAFB genes were associated with LF hypertrophy in patients with AIS. These phenomena are likely to be associated with the progression of scoliosis.

Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture.

Intervertebral disc (IVD) diseases are common spinal disorders that cause neck or back pain in the presence or absence of an underlying neurological disorder. IVD diseases develop on the basis of degeneration, and there are no established treatments for degeneration. IVD diseases may therefore represent a candidate for the application of regenerative medicine, potentially employing normal human dermal fibroblasts (NHDFs) induced to differentiate into nucleus pulposus (NP) cells. Here, we used a three-dimensional culture system to demonstrate that ectopic expression of MYC, KLF4, NOTO, SOX5, SOX6, and SOX9 in NHDFs generated NP-like cells, detected using Safranin-O staining. Quantitative PCR, microarray analysis, and fluorescence-activated cell sorting revealed that the induced NP cells exhibited a fully differentiated phenotype. These findings may significantly contribute to the development of effective strategies for treating IVD diseases.

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.

Morphological characteristics of DISH in patients with OPLL and its association with high-sensitivity CRP: inflammatory DISH.

OBJECTIVES: To characterize and clarify evidence as to whether the ectopic bone formations of DISH in patients with ossification of the posterior longitudinal ligament (OPLL) are caused by inflammatory or degenerative processes. METHODS: Whole-spine CT and serum high-sensitivity CRP (hs-CRP) levels were obtained from 182 cervical OPLL patients (DISH+, n = 104; DISH-, n = 78). In the DISH+ group, ectopic bone formations were categorized into Flat and Jaggy types, then further divided into three subgroups: group 1 (Jaggy-dominant pattern), group 2 (Equivalence of pattern) and group 3 (Flat-dominant pattern). Data were compared between the DISH+ and DISH- groups, and among the three subgroups. RESULTS: The upper thoracic spine was most affected by the Flat type, whereas the Jaggy type was more frequent in the middle and lower thoracic regions. There was no difference in hs-CRP levels between the DISH+ and DISH- groups. Among the three subgroups, hs-CRP levels in group 3 [mean (s.d.) 0.16 (0.09) mg/dl] were significantly higher than in group 1 [0.04 (0.02) mg/dl] and group 2 [0.08 (0.06) mg/dl]. Higher levels of hs-CRP were associated with a greater number of vertebral units with Flat-type formations (ß = 0.691, P < 0.0001) and with a lesser number of vertebral units with Jaggy-type formations (ß = -0.147, P = 0.036). CONCLUSION: The Flat type in DISH might be caused by an inflammatory pathogenesis rather than a degenerative process presented in the Jaggy type.

Serum Periostin Level Reflects Progression of Ossification of the Posterior Longitudinal Ligament.

Ossification of the posterior longitudinal ligament (OPLL), characterized by ectopic new bone formation in the spinal ligament, causes neurological impairment due to narrowing of the spinal canal. However, the etiology has not been fully elucidated yet. Several biomarkers may be related to the pathogenesis of OPLL. The present study focused on the serum level of periostin, which is recognized as an important bone formation regulator. METHODS: This study included 92 patients with OPLL and 54 control patients without OPLL. For the case-control analysis, 54 age and sex-matched patients were randomly included in the OPLL group. The serum fibroblast growth factor-23 (FGF-23), creatinine, inorganic phosphate, calcium, alkaline phosphatase, and periostin levels were assessed. Furthermore, the calcium, creatinine, and inorganic phosphate levels in urine and the percentage of tubular reabsorption of phosphate were also analyzed. Moreover, the relationship between the biomarkers and the extent of OPLL was analyzed. The data were compared between patients with OPLL progression (the progression group) and without OPLL progression (the non-progression group). RESULTS: The mean serum FGF-23 and periostin levels in the OPLL group were higher than that in the control group. The serum inorganic phosphate level in the OPLL group was lower than that in the control group. No correlation was found between any of the biomarkers and the extent of ossification. The serum periostin level in the progression group was higher than that in the non-progression group. No significant difference in the serum FGF-23 level was noted between the progression and non-progression groups. Moreover, no correlation was found between serum periostin and FGF-23 levels. CONCLUSIONS: The serum periostin level is related to OPLL progression. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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).

Accuracy of pedicle screw placement using patient-specific template guide system.

BACKGROUND: Despite repeated efforts for accurate cervical pedicle screw insertion, malpositioning of the inserted screw is commonly noted. To avoid neurovascular complications during cervical pedicle screw insertion, we have developed a new patient-specific screw guide system. This study aimed to evaluate the accuracy of cervical PS placement using the new patient-specific screw guide system. METHODS: This study is a retrospective clinical evaluation of prospectively enrolled patients. Seventeen consecutively enrolled patients who underwent posterior cervical fusion using the guide system were included. Firstly, three-dimensional planning of pedicle screw placement was done using simulation software. A screw guide for each vertebra was constructed preoperatively. A total of 77 screws were inserted with the guides. Postoperative computed tomography was used to evaluate pedicle perforation, and screw deviations, between the planned and actual screw positions, were measured. RESULTS: A total of 76 screws (98.7%) were completely inside the pedicle (C3-7), without neurovascular injuries. The mean screw deviations from the planned trajectory at the narrowest point of the pedicle and at the entry point in the axial and sagittal planes were 0.56 ± 0.43 mm and 0.43 ± 0.35 mm and 0.43 ± 0.30 mm and 0.63 ± 0.50 mm, respectively. There were no significant differences in any parameter at different spinal levels. Angular deviations in the sagittal and axial planes were 2.94 ± 2.04° and 2.53 ± 1.85°, respectively. Sagittal angular deviations tended to increase in the cranial vertebra (C3 and C4) compared to the middle cervical spine. CONCLUSIONS: We demonstrated that our patient-specific screw guide is vital for guiding precise screw insertion in the cervical pedicle. This technique may be an effective solution for achieving precise screw insertion and reducing the incidence of complications.

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.

Increase of the Serum FGF-23 in Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: Case-control study. OBJECTIVES: To determine the possible pathogenesis of ossification of the posterior longitudinal ligament (OPLL) in regard to the serum concentration of fibroblast growth factor 23 (FGF-23). METHODS: The study included 95 patients with OPLL and a control group of 73 age- and sex-matched volunteers. The serum concentrations of FGF-23, creatinine (Cre), alkaline phosphatase, calcium (Ca), inorganic phosphate (Pi), and hypersensitive C-reactive protein (hs-CRP) were analyzed from blood samples, and Cre, Ca, Pi, and tubular reabsorption of phosphate were measured using urine samples. We evaluated the severity of ossified spinal lesions in patients with OPLL according to the ossification index (the OP index and the OS index). Data was compared between the OPLL and control group and between the OPLL progression and no progression group. RESULTS: Serum FGF-23 and hs-CRP were higher, and serum Pi was lower in patients with OPLL than in the controls. There was a positive correlation between FGF-23 and hs-CRP and a negative correlation between serum Pi and the OS index; however, the correlations were very weak. Overall, 31.7% of patients had progression of OPLL during follow-up. FGF-23 and hs-CRP were higher in the progression group than in the no progression group. CONCLUSIONS: These results might indicate that FGF-23 and hs-CRP are positive markers for OPLL. Phosphate metabolism via FGF-23 might be a target for future study on the pathogenesis of OPLL.