Risk factors for early reoperation in patients after posterior lumbar interbody fusion surgery. A propensity-matched cohort analysis.

BACKGROUND: Reoperation is usually associated with poor results and increased morbidity and hospital costs. However, the rates, causes, and risk factors for reoperation in patients undergoing lumbar spinal fusion surgery remain controversial. This study aimed to identify the risk factors for early reoperation after posterior lumbar interbody fusion surgery and to compare the clinical outcomes between patients who underwent reoperation and those who did not. METHODS: We investigated a multicenter medical record database of 1263 patients who underwent posterior lumbar interbody fusion surgery between 2012 and 2015. A total of 72 (5.7%) reoperations within two years after surgery were identified and were propensity-matched for age, sex, number of fusion segments, and surgeon's experience. RESULTS: We analyzed a total of 114 patients (57 who underwent reoperation (R group) and 57 who did not (C group)). The mean age was 62.6 ± 13.4 years, with 78 men and 36 women. The mean number of fused segments was 1.2 ± 0.5. Surgical site infection was the most common cause of reoperation. There were significant differences in the incidence of diabetes mellitus (p = 0.024), preoperative ambulation status (p = 0.046), and ASA grade (p < 0.001) between the C and R groups. The recovery rate of the Japanese Orthopaedic Association score was significantly lower in the R group compared to the C group (R: 50.5 ± 28.8%, C: 63.9 ± 33.7%, p = 0.024). There were significant differences in the bone fusion rate (R: 63.2%, C: 96.5%, p < 0.001) and incidence of screw loosening (R: 31.6%; C: 10.5%; p = 0.006). CONCLUSION: Diabetes mellitus, preoperative ambulation status, and ASA grade were significant risk factors for early reoperation following posterior lumbar interbody fusion surgery. The patients who underwent early reoperation had worse clinical outcomes than those who did not.

Minimally Invasive Spinal Treatment (MIST)-A New Concept in the Treatment of Spinal Diseases: A Narrative Review.

In the past two decades, minimally invasive spine surgery (MISS) techniques have been developed for spinal surgery. Historically, minimizing invasiveness in decompression surgery was initially reported as a MISS technique. In recent years, MISS techniques have also been applied for spinal stabilization techniques, which were defined as minimally invasive spine stabilization (MISt), including percutaneous pedicle screws (PPS) fixation, lateral lumbar interbody fusion, balloon kyphoplasty, percutaneous vertebroplasty, cortical bone trajectory, and cervical total disc replacement. These MISS techniques typically provide many advantages such as preservation of paraspinal musculature, less blood loss, a shorter operative time, less postoperative pain, and a lower infection rate as well as being more cost-effective compared to traditional open techniques. However, even MISS techniques are associated with several limitations including technical difficulty, training opportunities, surgical cost, equipment cost, and radiation exposure. These downsides of surgical treatments make conservative treatments more feasible option. In the future, medicine must become "minimally invasive" in the broadest sense-for all patients, conventional surgeries, medical personnel, hospital management, nursing care, and the medical economy. As a new framework for the treatment of spinal diseases, the concept of minimally invasive spinal treatment (MIST) has been proposed.

Complications after spinal fixation surgery for osteoporotic vertebral collapse with neurological deficits: Japan Association of Spine Surgeons with ambition multicenter study.

BACKGROUND: There have been few reports on the incidence and risk factors of the complications after spinal fixation surgery for osteoporotic vertebral collapse (OVC) with neurological deficits. This study aimed to identify the incidence and risk factors of the complications after OVC surgery. METHODS: In this retrospective multicenter study, a total of 403 patients (314 women and 89 men; mean age 73.8 years) who underwent spinal fixation surgery for OVC with neurological deficits between 2005 and 2014 were enrolled. Data on patient demographics were collected, including age, sex, body mass index, smoking, steroid use, medical comorbidities, and surgical procedures. All postoperative complications that occurred within 6 weeks were recorded. Patients were classified into two groups, namely, complication group and no complication group, and risk factors for postoperative complications were investigated by univariate and multivariate analyses. RESULTS: Postoperative complications occurred in 57 patients (14.1%), and the most common complication was delirium (5.7%). In the univariate analysis, the complication group was found to be older (p = 0.039) and predominantly male (p = 0.049), with higher occurrence rate of liver disease (p = 0.001) and Parkinson's disease (p = 0.039) compared with the no-complication group. In the multivariate analysis, the significant independent risk factors were age (p = 0.021; odds ratio [OR] 1.051, 95% confidence interval [CI] 1.007-1.097), liver disease (p < 0.001; OR 8.993, 95% CI 2.882-28.065), and Parkinson's disease (p = 0.009; OR 3.636, 95% CI 1.378-9.599). CONCLUSIONS: Complications after spinal fixation surgery for OVC with neurological deficits occurred in 14.1%. Age, liver disease, and Parkinson's disease were demonstrated to be independent risk factors for postoperative complications.

Discography aids definitive diagnosis of posterior epidural migration of lumbar disc fragments: case report and literature review.

BACKGROUND: Posterior epidural migration of lumbar disc fragments (PEMLDF) is extremely rare. It is often confused with other posterior lesions and is usually diagnosed intraoperatively. We here describe the use of preoperative discography in the diagnosis of PEMLDF. CASE PRESENTATION: A 78-year-old man presented with acute low back pain, gait disturbance, and paresthesia in both legs. Magnetic resonance imaging showed a mass located posteriorly and laterally to the left aspect of the dural sac at the L3 level. The initial diagnosis indicated PEMLDF, malignancy, spontaneous hematoma, or epidural abscess. L3/4 discography clearly showed leakage of the contrast medium into the posterior dural space, indicating PEMLDF. The lesion was identified intraoperatively as a herniated-disc fragment, consistent with the preoperative discography. CONCLUSION: PEMDLF is difficult to diagnose preoperatively. Discography is useful for the definitive diagnosis of PEMDLF prior to surgery.

Presence of Modic type 1 change increases risk of postoperative pyogenic discitis following decompression surgery for lumbar canal stenosis.

STUDY DESIGN: Multicenter retrospective study. BACKGROUND: Postoperative surgical site infection is one of the most serious complications following spine surgery. Previous studies do not appear to have investigated pyogenic discitis following lumbar laminectomy without discectomy. This study aimed to identify risk factors for postoperative pyogenic discitis following lumbar decompression surgery. METHODS: We examined data from 2721 patients undergoing lumbar laminectomy without discectomy in five hospitals from April 2007 to March 2012. Patients who developed postoperative discitis following laminectomy (Group D) and a 4:1 matched cohort (Group C) were included. Fisher's exact test was used to determine risk factors, with values of p < 0.05 considered statistically significant. RESULTS: The cumulative incidence of postoperative discitis was 0.29% (8/2721 patients). All patients in Group D were male, with a mean age of 71.6 ± 7.2 years. Postoperative discitis was at L1/2 in 1 patient, at L3/4 in 3 patients, and at L4/5 in 4 patients. Except for 1 patient with discitis at L1/2, every patient developed discitis at the level of decompression. The associated pathogens were methicillin-resistant Staphylococcus aureus (n = 3, 37.5%), methicillin-susceptible Staphylococcus epidermidis (n = 1, 12.5%), methicillin-sensitive S. aureus (n = 1, 12.5%), and unknown (n = 3, 37.5%). In the analysis of risk factors for postoperative discitis, Group D showed a significantly lower ratio of patients who underwent surgery in the winter and a significantly higher ratio of patients who had Modic type 1 in the lumbar vertebrae compared to Group C. CONCLUSIONS: Although further prospective studies, in which other preoperative modalities are used for the evaluation, is needed, our data suggest the presence of Modic type 1 as a risk factor for discitis following laminectomy. Latent pyogenic discitis should be carefully ruled out in patients with Modic type 1. If lumbar laminectomy is performed for such patients, more careful observation is necessary to prevent the development of postoperative discitis.

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development.

Here we examined the involvement of Notch signaling in the endochondral ossification process, which is crucial for osteoarthritis (OA) development. Intracellular domains of Notch1 and -2 were translocated into the nucleus of chondrocytes with their differentiation in mouse limb cartilage and in mouse and human OA articular cartilage. A tissue-specific inactivation of the Notch transcriptional effector recombination signal binding protein for Ig kappa J (RBPjκ) in chondroprogenitor cells of SRY-box containing gene 9 (Sox9)-Cre;Rbpj(fl/fl) mouse embryos caused an impaired terminal stage of endochondral ossification in the limb cartilage. The RBPjκ inactivation in adult articular cartilage after normal skeletal growth using type II collagen (Col2a1)-Cre(ERT);Rbpj(fl/fl) mice by tamoxifen injection caused resistance to OA development in the knee joint. Notch intracellular domain with the effector RBPjκ stimulated endochondral ossification through induction of the target gene Hes1 in chondrocytes. Among the Notch ligands, Jagged1 was strongly induced during OA development. Finally, intraarticular injection of N-[N-(3,5-diflurophenylacetate)-L-alanyl]-(S)-phenylglycine t-butyl ester (DAPT), a small compound Notch inhibitor, to the mouse knee joint prevented OA development. The RBPjκ-dependent Notch signaling in chondrocytes modulates the terminal stage of endochondral ossification and OA development, representing an extracellular therapeutic target of OA.

Epidemiological survey of ossification of the posterior longitudinal ligament by using clinical investigation registration forms.

BACKGROUND: In Japan, ossification of the posterior longitudinal ligament (OPLL) has been designated as an intractable disease by the Ministry of Health, Labour, and Welfare. Here we aimed to clarify the epidemiological characteristics of severe OPLL patients by analyzing a national registry of this disease that uses clinical investigation registration forms. METHODS: We retrospectively investigated clinical investigation registration forms for 24,502 patients with OPLL. We examined the sex distribution, age of disease onset, period from disease onset to registration, family history, site of ossification as determined by plain radiographs, Japanese Orthopaedic Association score, and number of OPLL surgeries. RESULTS: The male-to-female ratios were 2.7:1 and 1.9:1 for new and renewed registrations, respectively. The mean ages at disease onset were 61.1 and 59.7 years for new and renewed registrations, respectively. The mean periods from disease onset to registration were 2.6 and 8.4 years for new and renewed registrations, respectively. The percentages of new registrations with and without family history were 5.3% and 51.5%, respectively (unknown for 43.3%). Of the new registrations, 3511, 359, and 200 cases exhibited ossification in the cervical spine, thoracic spine, and lumbar spine, respectively; the corresponding numbers for renewed registrations were 13,710, 2484, and 1508. The Japanese Orthopaedic Association score was 9.9 ± 3.6 for new registrations, and the mean score recovery rate for renewed registrations was 6.0%. The number of OPLL surgeries was one or zero, two, three, four, or five for 21,785, 2167, 412, 99, and 39 patients, respectively, with 11.1% of all patients having undergone multiple surgeries. CONCLUSIONS: This study offers new insight into the epidemiological characteristics of severe OPLL. In particular, we found that the age of disease onset was higher than previously reported, the period from disease onset to registration (surgery) was relatively short, and about 90% of the patients required only a single surgery.

A Novel Percutaneous Guide Wire (S-Wire) for Percutaneous Pedicle Screw Insertion: Its Development, Efficacy, and Safety.

PURPOSE: Minimally invasive spine stabilization (MISt) procedures, including MIS-transforaminal lumbar interbody fusion (MIS-TLIF), rely on precise placement of percutaneous pedicle screws (PPS). Serious intraoperative complications associated with PPS placement include great vessel and bowel injuries due to the guide-wire's anterior migration and penetration through the anterior aspect of the vertebral body. To address this issue, we developed a novel percutaneous guide wire (S-wire) and compared the biomechanical characteristics of S-wire and conventional wire in cadaveric spines, and to evaluate the S-wire's efficacy and safety in a clinical trial. METHODS: The S-wire is hollow, with braided wires extending at one tip. We compared the push-out and penetration forces of the S-wire and conventional wire in fresh cadaveric lumbar spines, from L1 to L5. RESULTS: Push-out forces caused the braided tip of the S-wire to bend or spread, and thus to resist anterior migration. The mean push-out forces for the S-wire and conventional wire were 15.5 ± 1.9 and 5.7 ± 0.8 N, respectively (P < .0001); the mean penetration forces were 69.1 ± 4.2 and 37.1± 4.8 N, respectively (P < .0005). There was no wire breakage or anterior-wall penetration in a clinical trial of 922 S-wires; interestingly, the pull-out force increased in 780 (84.6%) S-wires after placement. CONCLUSIONS: The mean push-out and penetration forces for the S-wire were approximately 3 and 2 times greater than those of conventional wire, respectively. The S-wire effectively prevented guide-wire anterior migration and penetration of the anterior vertebral-body wall. The S-wire device should effectively improve the safety of MISt procedures, including MIS-TLIF and percutaneous kyphoplasty in selected patient with osteoporosis.

Risk factors for adjacent segment disease after posterior lumbar interbody fusion and efficacy of simultaneous decompression surgery for symptomatic adjacent segment disease.

STUDY DESIGN: A retrospective study. SUMMARY OF BACKGROUND DATA: Posterior lumbar interbody fusion (PLIF) increases mechanical stress and can cause degenerative changes at the adjacent segment. However, the precise causes of adjacent segment disease (ASD) after PLIF are not known, and it is unclear whether simultaneous decompression surgery for symptomatic ASD is effective. OBJECTIVE: To study, radiographically and symptomatically, the risk factors for adjacent segment disease (ASD) in the lumbar spine after L4/5 PLIF and to examine whether decompression surgery for the adjacent segment (L3/4) reduces the occurrence of symptomatic ASD. METHODS: Fifty-four patients who underwent L4/5 PLIF for L4 degenerative spondylolisthesis and could be followed up for at least 2 years were included. Of these, 37 were treated simultaneously with decompression surgery at L3/4. We measured radiographic changes and assessed symptoms from the cranial adjacent segment. RESULTS: Thirty-one patients (57.4%) met radiologic criteria for ASD. The length of follow-up (P=0.004) and simultaneous decompression surgery at L3/4 (P=0.009) were statistically significant factors for radiologic diagnosis of ASD. Seven patients (13.0%) had symptomatic ASD: 6 in the decompression group (16.2%) and 1 in the PLIF-only group (5.9%). Simultaneous decompression surgery did not reduce the incidence of symptomatic ASD (P=0.256). Local lordosis at the fused segment (P=0.005) and the sagittal angle of the facet joint at L3/4 (P=0.024) were statistically significant predictors of symptomatic ASD, which was accompanied by postoperative anterior listhesis above the fused segment (S group, 8.4%±8.0%; nonsymptomatic group: -0.7%±5.0%, P=0.024). CONCLUSIONS: Patients whose facet joint at the adjacent segment had a more sagittal orientation had postoperative anterior listhesis, which caused symptomatic ASD. Simultaneous decompression surgery without fusion at the adjacent level was not effective for these patients, but rather, there was a possibility that it induced symptomatic ASD.

High preoperative hemoglobin A1c is a risk factor for surgical site infection after posterior thoracic and lumbar spinal instrumentation surgery.

BACKGROUND: Diabetes mellitus (DM) is reported to be a risk factor for surgical site infection (SSI), which is a serious complication after spinal surgery. The effect of DM on SSI after instrumented spinal surgery remains to be clarified. The aim was to elucidate perioperative risk factors for infection at the surgical site after posterior thoracic and lumbar spinal arthrodesis with instrumentation in patients with DM. METHODS: Consecutive patients who underwent posterior instrumented thoracic and lumbar spinal arthrodesis during the years 2005-2011, who could be followed for at least 1 year after surgery, were included. These included 36 patients with DM (19 males and 17 females; mean age 64.3 years). The patients' medical records were retrospectively reviewed to determine the SSI rate. The characteristics of the DM patients were examined in detail, including the levels of serum glucose and HbA1c, which indicate the level of diabetes control. RESULTS: Patients with DM had a higher rate of SSI (6 of 36 patients, 16.7 %) than patients without DM (10 of 309 patients, 3.2 %). Although the perioperative serum glucose level did not differ between DM patients that did or did not develop SSI, the preoperative HbA1c value was significantly higher in the patients who developed SSI (7.6 %) than in those who did not (6.9 %). SSI developed in 0.0 % of the patients with controlled diabetes (HbA1c <7.0 %) and in 35.3 % of the patients with uncontrolled diabetes (HbA1c ≥7.0 %). CONCLUSIONS: DM patients whose blood glucose levels were poorly controlled before surgery were at high risk for SSI. To prevent SSI in DM patients, we recommend lowering the HbA1c to <7.0 % before performing surgery.

Spinal coronal profiles and proximal femur bone mineral density in adolescent idiopathic scoliosis.

PURPOSE: Although the occurrence and progression of AIS has been linked to low bone mineral density (BMD), the relationships between spinal curvature and bilateral differences in proximal femur BMD are controversial. Few correlation studies have stratified patients by curve type. The purpose of this study was to evaluate the relationships between spinal coronal profile and bilateral differences in proximal femur BMD in patients with adolescent idiopathic scoliosis (AIS). METHODS: This study included 67 patients with AIS who underwent posterior correction and fusion surgery between January 2009 and October 2011. The mean age at the time of surgery was 17.4 ± 4.1 years. Bilateral proximal femur BMD was measured before surgery by dual-energy X-ray absorptiometry. We compared the proximal femur BMDs by determining the bilateral BMD ratio (left proximal femur BMD divided by that of the right). We evaluated correlations between coronal parameters, obtained from preoperative radiographs, and the BMD ratio using Pearson's correlation analysis. RESULTS: Patients with Lenke type 1 curve (48; all with a right convex curve) had a mean bilateral proximal femur BMD ratio of 1.00 ± 0.04. Patients with Lenke type 5 curve (19; all with a left convex curve) had a mean bilateral proximal femur BMD ratio of 0.94 ± 0.04, indicating that the BMD in the proximal femur on the right side (concave) was greater than that in the left (convex). Coronal balance was significantly correlated with the BMD ratio in both the Lenke type 1 and type 5 groups, with a correlation coefficient of 0.46 and 0.50, respectively. CONCLUSIONS: The bilateral proximal femur BMD ratio was significantly correlated with the coronal balance in AIS patients. When the C7 plumb line was shifted toward one side, the BMD was greater in the contralateral proximal femur.

Persistent Orthostatic Hypotension Following Surgery for Adult Spinal Deformity: Prevalence, Risk Factors, and Cardiovascular Evaluation.

STUDY DESIGN: Retrospective case-control study. PURPOSE: To understand the prevalence of persistent orthostatic hypotension (POH), as well as its risk factors and cardiovascular pathology, in patients receiving surgery for the adult spinal deformity (ASD). OVERVIEW OF LITERATURE: Although reports of the incidence of and risk factors for POH in different spinal disorders have recently been published, we are not aware of the comprehensive evaluation of POH following surgery for ASD. METHODS: We examined medical records from a single central database for 65 patients receiving surgical treatment for ASD. Statistical comparisons were made between patients who experienced postoperative POH and those who did not, by examining patient and operative characteristics, such as age, sex, comorbidities, functional status, preoperative neurological function, vertebral fractures, three-column osteotomy, total operative time, estimated blood loss, length of stay, and radiographic parameters. The determinants of POH were assessed using multiple logistic regression. RESULTS: We showed that postoperative POH was a complication of ASD surgery, with a 9% incidence rate. Patients with POH were statistically considerably more likely to require supported walkers due to partial paralysis and to have comorbidities including diabetes and neurodegenerative disease (ND). Furthermore, ND was an independent risk factor for postoperative POH (odds ratio, 4.073; 95% confidence interval, 1.094-8.362; p =0.020). Moreover, perioperative evaluation of the inferior vena cava showed that patients with postoperative POH had preoperative congestive heart failure and had hypovolemia lower postoperative diameter of the inferior vena cava than patients without POH. CONCLUSIONS: Postoperative POH is a potential complication of ASD surgery. The most pertinent risk factor is having an ND. According to our study, patients who have surgery for ASD may experience alterations in their hemodynamics.

Three-dimensional phase-contrast magnetic resonance imaging for the detention of a small communicating defect in a patient with a spinal extradural arachnoid cyst: illustrative case.

BACKGROUND: Spinal extradural arachnoid cysts are thought to be pouches that communicate with the intraspinal subarachnoid space through a dural defect. The treatment for these cysts is resection of the cyst wall followed by obliteration of the communicating defect, which is often elusive. OBSERVATIONS: The authors report the case of a 22-year-old man with an extradural arachnoid cyst with claudication and progressive motor weakness. Regular magnetic resonance imaging (MRI) and computed tomography did not reveal the location of the defect in the cyst. However, three-dimensional (3D) phase-contrast MRI clearly indicated the location of the defect and the flow of cerebrospinal fluid into the cyst. These findings allowed the authors to perform the least invasive surgery; the patient recovered motor function and could walk more smoothly. LESSONS: 3D phase-contrast MRI can reveal a subtle dural defect in patients with spinal extradural arachnoid cysts.

Receptor activator of NF-kappaB (RANK) ligand induces ectodomain shedding of RANK in murine RAW264.7 macrophages.

Osteoclastogenesis is a highly sophisticated process that involves a variety of membrane-bound proteins expressed in osteoblasts and osteoclast precursors. Over the past several years, proteolytic cleavage and release of the ectodomain of membrane-bound proteins, also referred to as ectodomain shedding, has emerged as an important posttranslational regulatory mechanism for modifying the function of cell surface proteins. In line with this notion, several membrane-bound molecules involved in osteoclastogenesis, including CSF-1R and receptor activator of NF-kappaB ligand (RANKL), are proteolytically cleaved and released from the cell surface. In this study, we investigated whether receptor activator of NF-kappaB (RANK), one of the most essential molecules in osteoclastogenesis, undergoes ectodomain shedding. The results showed that RANK is released in the form of a soluble monomeric protein and that TNF-alpha-converting enzyme is involved in this activity. We also identified potential cleavage sites in the juxtamembrane domain of RANK and found that rRANKL induces RANK shedding in a macrophage-like cell line RAW264.7 via TNFR-associated factor 6 and MAPK pathways. Furthermore, we found that RANKL-induced osteoclastogenesis is accelerated in TNF-alpha-converting enzyme-deficient osteoclast precursors. These observations suggest the potential involvement of ectodomain shedding in the regulation of RANK functions and may provide novel insights into the mechanisms of osteoclastogenesis.

Improvement of Coxarthrosis Due to Realignment of Pelvic Retroversion Following Spinal Corrective Surgery: A Case Report.

CASE: A 70-year-old woman presented with severe trunk deformity, gait disturbance, and bilateral hip pain. Radiography and magnetic resonance imaging revealed severe spinal kyphosis, bilateral osteoarthritis of the hip joints, and lumbar canal stenosis. A 2-stage corrective surgery for the treatment of spinal kyphosis was performed. Subsequently, the spinopelvic alignment changed remarkably. The spinal symptoms and radiographic parameters improved postoperatively, and bilateral hip pain and range of motion also showed improvement. CONCLUSION: Corrective surgery for the treatment of degenerative spinal kyphosis affected the spinopelvic alignment, and the symptoms of simultaneous coxarthrosis also improved after the corrective surgery.

Effect of low body mass index on clinical recovery after fusion surgery for osteoporotic vertebral fracture: A retrospective, multicenter study of 237 cases.

A retrospective multicenter study. Body mass index (BMI) is recognized as an important determinant of osteoporosis and spinal postoperative outcomes; however, the specific impact of BMI on surgery for osteoporotic vertebral fractures (OVFs) remains inconclusive. This retrospective multicenter study investigated the impact of BMI on clinical outcomes following fusion surgery for OVFs. 237 OVF patients (mean age, 74.3 years; 48 men and 189 women) with neurological symptoms who underwent spinal fusion were included in this study. Patients were grouped by World Health Organization BMI categories: low BMI (<18.5 kg/m2), normal BMI (≥18.5 and <25 kg/m2), and high BMI (≥25 kg/m2). Patients' backgrounds, surgical method, radiological findings, pain measurements, activities of daily living (ADL), and postoperative complications were compared after a mean follow-up period of 4 years. As results, the proportion of patients able to walk independently was significantly smaller in the low BMI group (75.0%) compared with the normal BMI group (89.9%; P = .01) and the high BMI group (94.3%; P = .04). Improvement in the visual analogue scale for leg pain was significantly less in the low BMI group than the high BMI group (26.7 vs 42.8 mm; P = .046). Radiological evaluation, the Frankel classification, and postoperative complications were not significantly different among all 3 groups. Improvement of pain intensity and ADL in the high BMI group was equivalent or non-significantly better for some outcome measures compared with the normal BMI group. Leg pain and independent walking ability after fusion surgery for patients with OVFs improved less in the low versus the high BMI group. Surgeons may want to carefully evaluate at risk low BMI patients before fusion surgery for OVF because poor clinical results may occur.

PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts.

Cytokine signaling via various transcription factors regulates receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-mediated osteoclast differentiation from monocyte/macrophage lineage cells involved in propagation and resolution of inflammatory bone destruction. Protein inhibitor of activated STAT3 (PIAS3) was initially identified as a molecule that inhibits DNA binding of STAT3 and regulates many transcription factors through distinct mechanisms. To analyze PIAS3 function in osteoclasts in vivo, we have generated transgenic mice in which PIAS3 is specifically expressed in the osteoclast lineage using the tartrate-resistant acid phosphatase (TRAP) gene promoter. PIAS3 transgenic mice showed an osteopetrotic phenotype due to impairment of osteoclast differentiation. Overexpression of PIAS3 in RAW264.7 cells suppressed RANKL-induced osteoclastogenesis by inhibiting the expression of c-Fos and NFATc1. Interestingly, PIAS3 inhibits the transcriptional activity of microphthalmia-associated transcription factor (MITF) independent of sumoylation. Down-regulation of PIAS3 markedly enhances RANKL-mediated osteoclastogenesis in RAW264.7 cells. Furthermore, overexpression of PIAS3 in mouse primary osteoblast (POB), down-regulates RANKL expression induced by interleukin-6 (IL-6) cytokine family, and inhibits osteoclast formation from bone marrow macrophages (BMMs) in vitro coculture system. Down-regulation of PIAS3 leads to the accelerated expression of RANKL in POB stimulated with IL-6 and soluble IL-6 receptor (sIL-6R). Taken together, our results clearly indicate that PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts.

IL-27 abrogates receptor activator of NF-kappa B ligand-mediated osteoclastogenesis of human granulocyte-macrophage colony-forming unit cells through STAT1-dependent inhibition of c-Fos.

IL-27 was first discovered as a factor supporting initial Th1 immune responses. Subsequent studies revealed that this cytokine has pleiotropic effects, including inhibition of certain immune cells, a regulatory role in hemopoietic stem cell differentiation, and antitumor activities. However, the role of human IL (hIL)-27 in human osteoclast precursors and inflammatory bone disease is unclear. Here, we examined the direct effect of hIL-27 on human osteoclastogenesis. Human bone marrow cells cultured in MethoCult medium containing human (h) GM-CSF, human stem cell factor, and hIL-3 expressed Mac-1, c-kit, and c-Fms. These cells, called hCFU-GMs, also expressed the IL-27 receptor, an IL-27Ralpha (WSX-1)/gp130 heterodimer. Cultivation in hM-CSF and human receptor activator of NF-kappaB ligand induced the differentiation of tartrate-resistant acid phosphatase-positive multinucleated cells (osteoclasts) from hCFU-GMs, and hIL-27 inhibited this osteoclastogenesis in a dose-dependent manner. hIL-27 also repressed bone resorption by osteoclasts on a dentine slice. hIL-27 caused a remarkable increase in STAT1 phosphorylation and enhanced the STAT1 protein level. It also inhibited the expression of receptor activator of NF-kappaB ligand-induced c-Fos and cytoplasmic, calcineurin-dependent 1 NFAT (NFATc1), which are indispensable transcription factors for osteoclastogenesis. Fludarabine, a STAT1 inhibitor, and STAT1 small interfering RNA partially rescued the inhibition of osteoclastogenesis by IL-27. A WSX-1 deficiency caused severe inflammatory bone destruction primed by Escherichia coli cell wall lysate in vivo. Therefore, hIL-27 may act as an anti-inflammatory cytokine in human bone destruction, by inhibiting osteoclastogenesis from hCFU-GMs via STAT1-dependent down-regulation of the transcription factor c-Fos. Our results suggest that hIL-27 may prove useful as a therapeutic target for inflammatory bone destruction.

Risk Factor for Poor Patient Satisfaction After Lumbar Spine Surgery in Elderly Patients Aged Over 80 years.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To clarify the poor patient satisfaction after lumbar spinal surgery in elderly patients. SUMMARY OF BACKGROUND DATA: As the global population continues to age, it is important to consider the surgical outcome and patient satisfaction in the elderly. No studies have assessed patient satisfaction in elderly patients undergoing surgical treatment and risk factors for poor satisfaction in elderly patients after lumbar spinal surgery. MATERIALS AND METHODS: A retrospective multicenter survey was performed in 169 patients aged above 80 years who underwent lumbar spinal surgery. Patients were followed up for at least 1 year after surgery. We assessed patient satisfaction from the results of surgery by using a newly developed patient questionnaire. Patients were assessed by demographic data, surgical procedures, complications, reoperation rate, pain improvement, and risk factors for poor patient satisfaction with surgery for lumbar spinal disease. RESULTS: In total, 131 patients (77.5%, G-group) were satisfied and 38 patients (22.5%, P-group) were dissatisfied with surgery. The 2 groups did not differ significantly in baseline characteristics and surgical data. Postoperative visual analog scale score for low back pain and leg pain were significantly higher in the P-group than in the G-group (low back pain: G-group, 1.7±1.9 vs. P-group, 5.2±2.5, P<0.001; leg pain: G-group, 1.4±2.0 vs. P-group, 5.5±2.6, P<0.001). Multivariate regression analysis revealed that postoperative vertebral fracture (P=0.049; odds ratio, 3.096; 95% confidence interval, 1.004-9.547) and reoperation (P=0.025; odds ratio, 5.692; 95% confidence interval, 1.250-25.913) were significantly associated with the patient satisfaction after lumbar spinal surgery. CONCLUSIONS: Postoperative vertebral fracture and reoperation were found to be risk factors for poor patient satisfaction after lumbar spinal surgery in elderly patients, which suggests a need for careful treatment of osteoporosis in addition to careful determination of surgical indication and procedure in elderly patients. LEVEL OF EVIDENCE: Level III.

The Surgical Outcomes of Spinal Fusion for Osteoporotic Vertebral Fractures in the Lower Lumbar Spine with a Neurological Deficit.

INTRODUCTION: Osteoporotic vertebral fracture (OVF) is the most common osteoporotic fracture, and some patients require surgical intervention to improve their impaired activities of daily living with neurological deficits. However, many previous reports have focused on OVF around the thoracolumbar junction, and the surgical outcomes of lumbar OVF have not been thoroughly discussed. We aimed to investigate the surgical outcomes for lumbar OVF with a neurological deficit. METHODS: Patients who underwent fusion surgery for thoracolumbar OVF with a neurological deficit were enrolled at 28 institutions. Clinical information, comorbidities, perioperative complications, Japanese Orthopaedic Association scores, visual analog scale scores, and radiographic parameters were compared between patients with lower lumbar fracture (L3-5) and those with thoracolumbar junction fracture (T10-L2). Each patient with lower lumbar fracture (L group) was matched with to patients with thoracolumbar junction fracture (T group). RESULTS: A total 403 patients (89 males and 314 females, mean age: 73.8 ± 7.8 years, mean follow-up: 3.9 ± 1.7 years) were included in this study. Lower lumbar OVF was frequently found in patients with lower bone mineral density. After matching, mechanical failure was more frequent in the L group (L group: 64%, T group: 39%; p < 0.001). There was no difference between groups in the clinical and radiographical outcomes, although the rates of complication and revision surgery were still high in both groups. CONCLUSIONS: The surgical intervention for OVF is effective in patients with myelopathy or radiculopathy regardless of the surgical level, although further study is required to improve clinical and radiographical outcomes. LEVEL OF EVIDENCE: Level III.