ABSTRACT
Maintenance of bone homeostasis and the balance between bone resorption and formation are crucial for maintaining skeletal integrity. This study sought to investigate the role of salt-inducible kinase 3 (SIK3), a key regulator in cellular energy metabolism, during the differentiation of osteoclasts. Despite osteoclasts being high energy-consuming cells essential for breaking down mineralized bone tissue, the specific function of SIK3 in this process remains unclear. To address this issue, we generated osteoclast-specific SIK3 conditional knockout mice and assessed the impact of SIK3 deletion on bone homeostasis. Our findings revealed that SIK3 conditional knockout mice exhibited increased bone mass and an osteopetrosis phenotype, suggesting a pivotal role for SIK3 in bone resorption. Moreover, we assessed the impact of pterosin B, a SIK3 inhibitor, on osteoclast differentiation. The treatment with pterosin B inhibited osteoclast differentiation, reduced the numbers of multinucleated osteoclasts, and suppressed resorption activity in vitro. Gene expression analysis demonstrated that SIK3 deletion and pterosin B treatment influence a common set of genes involved in osteoclast differentiation and bone resorption. Furthermore, pterosin B treatment altered intracellular metabolism, particularly affecting key metabolic pathways, such as the tricarboxylic acid cycle and oxidative phosphorylation. These results provide valuable insights into the involvement of SIK3 in osteoclast differentiation and the molecular mechanisms underlying osteoclast function and bone diseases.
Osteoporosis is a disease that causes bones to become weak and fragile, increasing the risk of fractures especially in elderly. It is caused by an imbalance between the formation of new bone and the destruction of old bone. Cells called osteoclasts are responsible for breaking down old bone. Excessive osteoclast activity results in bone loss and osteoporosis. Our research has identified a LKB1-SIK3 pathway, which acts as an energy sensor in osteoclasts. We found that this pathway is activated when osteoclast activity is increased, and we were able to reduce osteoclast activity by genetically removing or inhibiting SIK3. These findings suggest that targeting the LKB1-SIK3 pathway may be a promising new approach for the treatment of osteoporosis. Developing drugs that inhibit SIK3 may slow bone loss and reduce the risk of fractures in osteoporotic patients.
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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.
ABSTRACT
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.
ABSTRACT
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.
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OBJECTIVE: Using segmental dynamic and static factors, we aimed to elucidate the pathogenesis and relationship between ossification of the posterior longitudinal ligament (OPLL) and the severity of cervical myelopathy. METHODS: Retrospective analysis of 163 OPLL patients' 815 segments. Imaging was used to evaluate each segmental space available for the spinal cord (SAC), OPLL diameter, type, bone space, K-line, the C2-7 Cobb angle, each segmental range of motion (ROM), and total ROM. Magnetic resonance imaging was used to evaluate spinal cord signal intensity. Patients were divided into the myelopathy group (M group) and the without myelopathy group (WM group). RESULTS: Minimal SAC (p = 0.043), (C2-7) Cobb angle (p = 0.004), total ROM (p = 0.013), and local ROM (p = 0.022) were evaluated as an independent predictor of myelopathy in OPLL. Different from the previous report, the M group had a straighter whole cervical spine (p < 0.001) and poorer cervical mobility (p < 0.001) compared to the WM group. Total ROM was not always a risk factor for myelopathy, as its impact depended on SAC, when SAC > 5 mm, the incidence rate of myelopathy decreased with the increase of total ROM. Lower cervical spine (C5-6, C6-7) showing increased "Bridge-Formation," along with spinal canal stenosis and segmental instability (C2-3, C3-4) in the upper cervical spine, could cause myelopathy in M group (p < 0.05). CONCLUSION: Cervical myelopathy is linked to the OPLL's narrowest segment and its segmental motion. The hypermobility of the C2-3 and C3-4, contributes significantly to the development of myelopathy in OPLL.
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BACKGROUND: Atypical fractures are caused by the combined effects of severe suppression of bone metabolism (SSBT) due to long-term bisphosphonate therapy and chronic repetitive bone microdamage. Atypical ulnar fractures (AUFs) due to SSBT are rare, and there is no standard treatment strategy for such fractures. The relevant literature was reviewed, and the treatment strategy for AUF is discussed. METHODS: A systematic review was conducted. All studies on ulnar fractures in individuals with a history of bisphosphonate use were included, and the data were extracted and analyzed from the perspective of the therapeutic strategy. RESULTS: Forty limbs of 35 patients were included. As for the treatment of AUF, 31 limbs were treated surgically, and conservative treatment with casting was performed for 9 limbs. The bone fusion rate was 22/40 (55.0%), and non-union was seen in all patients treated conservatively. There was a significant difference in the bone fusion rate between patients with surgical treatment and those with conservative treatment. The bone fusion rate of patients with parathyroid hormone (PTH) and surgery was 82.3% (14/17 limbs); the bone fusion rate with PTH and bone graft was 69.2% (9/13 limbs). However, there were no significant differences in the fusion rate in the groups with or without PTH, with or without bone grafting, or the combination of the two treatments. There was also no significant difference in the bone fusion rate in the groups with or without low-intensity pulsed ultrasound (LIPUS) treatment. CONCLUSIONS: Based on the literature review, surgery is necessary to achieve bone union, but surgery alone is not adequate to achieve bony union. Bone grafting and the administration of PTH and LIPUS may promote early bone fusion, but the present study did not show significant advantages of these additional treatments for bone union.
ABSTRACT
Ossification of the posterior longitudinal ligament (OPLL) is considered a multifactorial condition characterized by ectopic new bone formation in the spinal ligament. Recently, its connections with inflammation as well as sacroiliac (SI) joint ankylosis have been discussed. Nevertheless, whether inflammation, spinal ligament ossification, and SI joint changes are linked in OPLL has never been investigated. In this study, whole-spinal computed tomography and serum high-sensitive C-reactive protein (hs-CRP) levels were obtained in 162 patients with cervical OPLL. Ossification lesions were categorized as plateau and hill shapes. Accordingly, patients were divided into plateau-shaped (51 males and 33 females; mean age: 67.7 years) and hill-shaped (50 males and 28 females; mean age: 67.2 years) groups. SI joint changes were classified into four types and three subtypes, as previously described. Interactions among ossification shapes, hs-CRP levels, and morphological changes in the SI joint were investigated. The plateau shape was more common in the vertebral segments (59.5%), compared to the hill shape, which was predominant in the intervertebral regions (65.4%). Serum hs-CRP levels in the plateau-shaped group (0.11 ± 0.10 mg/dL) were significantly higher than those in the hill-shaped group (0.07 ± 0.08 mg/dL). SI joint intra-articular fusion was the main finding in the plateau-shaped group and showed significantly higher hs-CRP levels compared to the anterior para-articular bridging, which more frequently occurred in the hill-shaped group. Our findings suggested a possible inflammation mechanism that might contribute to the new bone formation in OPLL, particularly the plateau shape.
ABSTRACT
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.
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Purpose: We investigated the clinical outcomes of flexor tendon reconstruction for chronic rupture of the flexor tendon based on an evaluation of the voluntary active contraction distance (ACD) of the ruptured musculotendinous unit and changes in intraoperative total active motion (TAM) that could only be observed during wide-awake local anesthesia no tourniquet (WALANT) surgery. Methods: Reconstructions of 19 tendons of the flexor pollicis longus (FPL) and 18 tendons of the flexor digitorum profundus (FDP) were performed during WALANT surgery to evaluate the ACD of the ruptured musculotendinous unit and TAM observed during the surgery. Tendon grafting or tendon transfer was selected during the surgery based on ACD. TAM, pinch strength, and grip power were evaluated before the surgery, during the surgery, and at final follow-up, and they were surveyed based on Quick Disabilities of the Arm, Shoulder, and Hand (q-DASH) scores. The final outcomes of tendon grafting and tendon transfer were compared. Results: In FPL tendon reconstruction, tendon grafting was performed in 10 patients with a total PDD and ACD value greater than 30 mm, and tendon transfer was performed in 9 patients with the value less than 30 mm. In FDP tendon reconstruction, tendon grafting was performed in 8 patients and tendon repair in 2 patients with a total PDD and ACD value greater than 40 mm, and tendon transfer was performed in 8 patients with the value less than 40 mm. The TAM value, q-DASH score, pinch power, and grip strength were improved in all patients. In both the tendon reconstructions, intraoperative TAM was significantly increased compared with preoperative TAM but significantly decreased at final follow-up. No significant differences were identified in final follow-up TAM and the q-DASH scores between tendon transfer and tendon grafting. Conclusions: The great advantage of WALANT surgery is that surgeons can evaluate the ruptured musculotendinous unit and measure TAM during the surgery. Type of study/level of evidence: Therapeutic I.
ABSTRACT
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.
Subject(s)
Kyphosis , Scoliosis , Adolescent , Child , Disease Progression , Female , Humans , Male , Neural Networks, Computer , Pilot Projects , Scoliosis/surgeryABSTRACT
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.
Subject(s)
Ligamentum Flavum , Scoliosis , Adolescent , Gene Expression , Humans , Hypertrophy/genetics , Ligamentum Flavum/metabolism , Microarray Analysis , Scoliosis/diagnostic imaging , Scoliosis/geneticsABSTRACT
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.
Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Nucleus Pulposus , Fibroblasts/metabolism , Humans , Intervertebral Disc/metabolism , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/therapy , Intervertebral Disc Displacement , Nucleus Pulposus/metabolismABSTRACT
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.
Subject(s)
Scoliosis , Spinal Fusion , Surgeons , Adolescent , Analgesia, Patient-Controlled/methods , Analgesics, Opioid , Anesthetics, Local , Humans , Morphine , Pain, Postoperative/diagnosis , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Retrospective Studies , Scoliosis/etiology , Scoliosis/surgery , Spinal Fusion/adverse effects , Spinal Fusion/methodsABSTRACT
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.
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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.
Subject(s)
Hyperostosis, Diffuse Idiopathic Skeletal , Ossification of Posterior Longitudinal Ligament , Ossification, Heterotopic , C-Reactive Protein , Humans , Hyperostosis, Diffuse Idiopathic Skeletal/complications , Ossification of Posterior Longitudinal Ligament/complications , Ossification, Heterotopic/complications , Spine/pathologyABSTRACT
BACKGROUND: No anti-adhesive materials are currently in clinical use for orthopaedic surgery. We developed a hyperdry amniotic membrane (HD-AM) for easy storage and transplantation as amniotic membrane. The purpose of this study was to examine the application of HD-AM to reduce peritendinous adhesions without impairing tendon healing. METHODS: We randomly divided 3 digits (2nd, 3rd, and 4th digits) from each rabbit into three groups: a tendon repair group; a tendon repair with HD-AM group (HD-AM group); and a control group (cast only). The effects of HD-AM on peritendinous adhesions and tendon healing were examined using microscopic, histological, and mechanical analyses in a rabbit flexor digitorum profundus tendon model. RESULTS: Adhesions on macroscopic evaluation of the tendon repair site were significantly smaller in the HD-AM group than in the tendon repair group. Little adhesion formation or foreign body reactions were seen by on histologic evaluation in the HD-AM group. Range of motion following tendon repair was significantly better in the HD-AM group than in the tendon repair group. Maximal tensile strength required to pull the tendon from the site of adhesion was significantly smaller in the HD-AM group than in the tendon repair group. As for tendon repair site, no significant difference was seen between the tendon repair and HD-AM groups. CONCLUSIONS: HD-AM prevented peritendinous adhesion macroscopically, pathologically, and mechanically without impairing the sutured tendon. HD-AM has already been clinically applied in neurosurgery, ophthalmology, and otolaryngology, and clinical application as an anti-adhesive materials may be achieved in the future.
Subject(s)
Amnion , Tendon Injuries , Animals , Rabbits , Amnion/pathology , Tendon Injuries/prevention & control , Tendon Injuries/surgery , Tendons/pathology , Tendons/surgery , Tissue Adhesions/etiology , Tissue Adhesions/pathology , Tissue Adhesions/prevention & control , Wound HealingABSTRACT
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.
Subject(s)
Hyperostosis, Diffuse Idiopathic Skeletal/diagnostic imaging , Sacroiliac Joint/diagnostic imaging , Aged , Aged, 80 and over , Anatomic Variation , Female , Humans , Hyperostosis, Diffuse Idiopathic Skeletal/etiology , Hyperostosis, Diffuse Idiopathic Skeletal/pathology , Male , Retrospective Studies , Sacroiliac Joint/pathology , Tomography, X-Ray ComputedABSTRACT
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.
ABSTRACT
BACKGROUND: Although the pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear, there are little evidences of the pathogenesis in patients with thoracolumbar/lumbar AIS. The purpose of this study was to identify proteins or proteomes that may be causally related to the pathogenesis of AIS with structured thoracolumbar/lumbar curvature using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). METHODS: A total of 20 control volunteers and 61 AIS in patients with thoracolumbar/lumbar curvature were included. First, the plasma samples of each five AIS with pure thoracolumbar/lumbar curvature and control samples were subjected to 2D-DIGE analysis. Protein spots that were expressed differently by the AIS and control groups were selected and identified by nanoscale liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) analysis. To characterize the differently-expressed proteins in AIS patients, we performed functional pathway analysis using the Protein ANalysis THrough Evolutionary Relationships (PANTHER) system. Additionally, the proteins were compared between control and AIS using western blotting. Lastly, prospectively collected 15 control and 41 AIS with thoracolumbar/lumbar curvature samples were compared to the differentially expressed proteins. RESULTS: A total of 3862 ± 137 spots were detected, of which 11 spots met the criteria when compared with controls. Nine proteins were identified by nanoLC-MS/MS. Functional analysis showed the association of the proteins in AIS patients with blood coagulation using the PANTHER system. Of the proteins, vitamin D binding protein (DBP) significantly correlated with Cobb angle in thoracolumbar/lumbar curvatures. DBP expression of the prospectively collected AIS samples were significantly higher than those of controls (P < 0.05). CONCLUSIONS: This study suggests that DBP and several coagulation-related proteins may play a role in the pathogenesis of AIS. DBP appears to be a marker of severity of AIS with thoracolumbar/lumbar curvature.