The influence of costal resection on pulmonary function after total en bloc spondylectomy for spine tumor.

BACKGROUND: Total en bloc spondylectomy (TES) is one of the surgical procedures which has been recognized as a complete resection for spine tumors. Although the surgery achieves favorable local control for solitary spinal lesion, performing the procedure in the thoracic spine requires circumferential dissection around the vertebral body and bilateral rib resections which might result in decline of pulmonary function postoperatively. This study aimed to clarify whether the number of rib resections negatively impacts pulmonary function after the procedure. METHODS: This study included 31 patients who underwent vertebrectomy (17 males and 14 females) with a mean age of 54.2 years. Pulmonary function testing (PFT) was performed before surgery and at 1 month, 6 months, and 1 year postoperative visits. Patients with restrictive disorders such as space occupying lesions in the lung, obstructive problems such as a history of asthma, and smoking history were excluded from this study. Associations between the number of rib resections and PFT data were analyzed based on the resected level of the thoracic spine. RESULTS: There was a significant decrease in forced vital capacity (FVC) at 1 month (72% of preoperative value), followed by gradual recovery at 6 months (89%) and 1 year (90%). The percentage of predicted forced expiratory volume in 1 s remained stable. Patients who underwent three pairs of rib resections showed a significant decrease in the FVC (83.5% of the preoperative value) and FEV1 (82.1% of the preoperative value) compared with one or two pairs of rib resections. CONCLUSION: FVC decreased 1 month after vertebrectomy and returned to 90% of preoperative value at 1 year postoperatively. Three pairs of rib resections showed a significant decrease in FVC, suggesting the influence of a greater numbers of rib resections on pulmonary function.

Clinical outcomes and prognostic factors following the surgical resection of renal cell carcinoma spinal metastases.

The efficacy of surgical resection in metastatic renal cell carcinoma is an active and important research field in the postcytokine era. Bone metastases, especially in the spine, compromise patient performance status. Metastasectomy is indicated, if feasible, because it helps to achieve the best clinical outcomes possible compared with other treatments. This study examined the postoperative survival and prognostic factors in patients who underwent metastasectomy of spinal lesions. The retrospective study included 65 consecutive patients with metastatic renal cell carcinomas who were operated on by spinal metastasectomy between 1995 and 2017 at our institution. The cancer-specific survival times from the first spinal metastasectomy to death or the last follow-up (≥3 years) were determined using Kaplan-Meier analysis. Potential factors influencing survival were analyzed using Cox proportional hazard models. Planned surgical resection of all the spine tumors was achieved in all patients. Of these, 38 had complete metastasectomy of all visible metastases, including extraspinal lesions. In all patients, the estimated median cancer-specific survival time was 100 months. The 3-, 5-, and 10-year cancer-specific survival rates were 77%, 62%, and 48%, respectively. The survival times after spinal metastasectomy were similar in both cytokine and postcytokine groups. In multivariate analyses, postoperative disability, the coexistence of liver metastases, multiple spinal metastases, and incomplete metastasectomy were significant risk factors associated with short-term survival. Complete metastasectomy, including extraspinal metastases, was associated with improved cancer-specific survival. Proper patient selection and complete metastasectomy provide a better prognosis in metastatic renal cell carcinoma patients.

Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model.

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6-8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.

Indication for anterior spinal cord decompression via a posterolateral approach for the treatment of ossification of the posterior longitudinal ligament in the thoracic spine: a prospective cohort study.

PURPOSE: For ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine, anterior decompression is the most effective method for relieving spinal cord compression. The purpose of this study was to prospectively analyze the surgical outcomes based on our strategy in the treatment of thoracic OPLL. METHODS: This study included 23 patients who underwent surgery for thoracic OPLL based on the following strategy between 2011 and 2017. For patients with a beak-type OPLL in the kyphotic curve with a ≥ 50% canal occupying ratio, circumferential decompression via a posterolateral approach and fusion (CDF) was indicated. For other types of OPLL, posterior decompression and fusion (PDF) was commonly indicated. Posterior fusion without decompression (PF) was applied when the spinal cord was separated from the posterior spinal elements. Clinical and radiological outcomes were compared among the CDF, PDF, and PF groups with a minimum of 20-month follow-up. RESULTS: Ten, eleven, and two patients underwent CDF, PDF, and PF, respectively. The preoperative Japanese Orthopedic Association (JOA) score in the CDF group was significantly lower than that in the PDF group. The average recovery rate, according to JOA score, was 63%, 56%, and 25% in the CDF, PDF, and PF groups, respectively. The result in the CDF group was better than that in the PF group. CONCLUSIONS: Anterior decompression was appropriate for patients with localized spinal cord compression by a large OPLL in the kyphotic curve, and CDF via a posterolateral approach appears to be safe and effective. These slides can be retrieved under Electronic Supplementary Material.

The factors related to the poor ADL in the patients with osteoporotic vertebral fracture after instrumentation surgery.

PURPOSE: Osteoporotic vertebral fracture (OVF) with nonunion or neurological deficit may be a candidate for surgical treatment. However, some patients do not show improvement as expected. Therefore, we conducted a nationwide multicenter study to determine the predictors for postoperative poor activity of daily living (ADL) in patients with OVF. METHODS: We retrospectively reviewed the case histories of 309 patients with OVF who underwent surgery. To determine the factors predicting postoperative poor ADL, uni- and multivariate statistical analyses were performed. RESULTS: The frequency of poor ADL at final follow-up period was 9.1%. In univariate analysis, preoperative neurological deficit (OR, 4.1; 95% CI, 1.8-10.3; P < 0.001), perioperative complication (OR, 3.4; P = 0.006), absence of preoperative bone-modifying agent (BMA) administration (OR, 2.7; P = 0.03), and absence of postoperative recombinant human parathyroid hormone (rPTH) administration (OR, 3.9; P = 0.006) were significantly associated. In multivariate analysis, preoperative neurological deficit (OR, 4.6; P < 0.001), perioperative complication (OR, 3.4; P = 0.01), and absence of postoperative rPTH administration (OR, 3.9; P = 0.02) showed statistical significance. CONCLUSIONS: Preoperative neurological deficit, perioperative complication, and absence of postoperative rPTH administration were considered as predictors for postoperative poor ADL in patients with OVF. Neurological deficits and complications are often inevitable factors; therefore, rPTH is an important option for postoperative treatment for OVF. These slides can be retrieved under Electronic Supplementary Material.

Effect of bisphosphonates or teriparatide on mechanical complications after posterior instrumented fusion for osteoporotic vertebral fracture: a multi-center retrospective study.

BACKGROUND: The optimal treatment of osteoporosis after reconstruction surgery for osteoporotic vertebral fractures (OVF) remains unclear. In this multicentre retrospective study, we investigated the effects of typically used agents for osteoporosis, namely, bisphosphonates (BP) and teriparatide (TP), on surgical results in patients with osteoporotic vertebral fractures. METHODS: Retrospectively registered data were collected from 27 universities and affiliated hospitals in Japan. We compared the effects of BP vs TP on postoperative mechanical complication rates, implant-related reoperation rates, and clinical outcomes in patients who underwent posterior instrumented fusion for OVF. Data were analysed according to whether the osteoporosis was primary or glucocorticoid-induced. RESULTS: A total of 159 patients who underwent posterior instrumented fusion for OVF were included. The overall mechanical complication rate was significantly lower in the TP group than in the BP group (BP vs TP: 73.1% vs 58.2%, p = 0.045). The screw backout rate was significantly lower and the rates of new vertebral fractures and pseudoarthrosis tended to be lower in the TP group than in the BP group. However, there were no significant differences in lumbar functional scores and visual analogue scale pain scores or in implant-related reoperation rates between the two groups. The incidence of pseudoarthrosis was significantly higher in patients with glucocorticoid-induced osteoporosis (GIOP) than in those with primary osteoporosis; however, the pseudoarthrosis rate was reduced by using TP. The use of TP also tended to reduce the overall mechanical complication rate in both primary osteoporosis and GIOP. CONCLUSIONS: The overall mechanical complication rate was lower in patients who received TP than in those who received a BP postoperatively, regardless of type of osteoporosis. The incidence of pseudoarthrosis was significantly higher in patients with GIOP, but the use of TP reduced the rate of pseudoarthrosis in GIOP patients. The use of TP was effective to reduce postoperative complications for OVF patients treated with posterior fusion.

Short- versus long-segment posterior spinal fusion with vertebroplasty for osteoporotic vertebral collapse with neurological impairment in thoracolumbar spine: a multicenter study.

BACKGROUND: Vertebroplasty with posterior spinal fusion (VP + PSF) is one of the most widely accepted surgical techniques for treating osteoporotic vertebral collapse (OVC). Nevertheless, the effect of the extent of fusion on surgical outcomes remains to be established. This study aimed to evaluate the surgical outcomes of short- versus long-segment VP + PSF for OVC with neurological impairment in thoracolumbar spine. METHODS: We retrospectively collected data from 133 patients (median age, 77 years; 42 men and 91 women) from 27 university hospitals and their affiliated hospitals. We divided patients into two groups: a short-segment fusion group (S group) with 2- or 3-segment fusion (87 patients) and a long-segment fusion group (L group) with 4- through 6-segment fusion (46 patients). Surgical invasion, clinical outcomes, local kyphosis angle (LKA), and complications were evaluated. RESULTS: No significant differences between the two groups were observed in terms of neurological recovery, pain scale scores, and complications. Surgical time was shorter and blood loss was less in the S group, whereas LKA at the final follow-up and correction loss were superior in the L group. CONCLUSION: Although less invasiveness and validity of pain and neurological relief are secured by short-segment VP + PSF, surgeons should be cautious regarding correction loss.

Abdominal trunk muscle weakness and its association with chronic low back pain and risk of falling in older women.

BACKGROUND: Previous studies have indicated that trunk muscle strength decreases with chronic low back pain, and is associated with poor balance, poor functional performance, and falls in older adults. Strengthening exercises for chronic low back pain are considered the most effective intervention to improve functional outcomes. We developed an innovative exercise device for abdominal trunk muscles that also measures muscle strength. The correlation between muscle weakness, as measured by our device, the presence of chronic low back pain, and decreased physical ability associated with a risk of falling were evaluated in older women. METHODS: Thirty-eight elderly women, who could walk without support during daily activities and attended our outpatient clinic for treatment of chronic low back pain, knee or hip arthritis, or osteoporosis, were included in this study. Anthropometric measurements were performed. Grip power and one-leg standing time with eyes open were measured, and abdominal trunk muscle strength was measured using our device. History of falling in the previous 12 months was noted. Subjects with chronic low back pain (visual analog scale score ≥ 20 mm) for over 3 months were assigned to the low back pain group (n = 21). The remaining subjects formed the non-low back pain group (n = 17). RESULTS: Abdominal muscle strength of subjects in the low back pain group, and with history of falling, was significantly lower compared with that of subjects in the non-low back pain group, and in subjects without a history of falling, respectively. There was a moderate positive correlation between abdominal trunk muscle strength and one-leg standing time with eyes open. CONCLUSION: We measured abdominal muscle strength in older women with chronic low back pain using our device, and it was significantly lower than that of those without chronic low back pain. Muscle weakness was associated with a history and risk of falling.

Surgical outcomes of spinal fusion for osteoporotic thoracolumbar vertebral fractures in patients with Parkinson's disease: what is the impact of Parkinson's disease on surgical outcome?

BACKGROUND: To date, there have been little published data on surgical outcomes for patients with PD with thoracolumbar OVF. We conducted a retrospective multicenter study of registry data to investigate the outcomes of fusion surgery for patients with Parkinson's disease (PD) with osteoporotic vertebral fracture (OVF) in the thoracolumbar junction. METHODS: Retrospectively registered data were collected from 27 universities and their affiliated hospitals in Japan. In total, 26 patients with PD (mean age, 76 years; 3 men and 23 women) with thoracolumbar OVF who underwent spinal fusion with a minimum of 2 years of follow-up were included (PD group). Surgical invasion, perioperative complications, radiographic sagittal alignment, mechanical failure (MF) related to instrumentation, and clinical outcomes were evaluated. A control group of 296 non-PD patients (non-PD group) matched for age, sex, distribution of surgical procedures, number of fused segments, and follow-up period were used for comparison. RESULTS: The PD group showed higher rates of perioperative complications (p < 0.01) and frequency of delirium than the non-PD group (p < 0.01). There were no significant differences in the degree of kyphosis correction, frequency of MF, visual analog scale of the symptoms, and improvement according to the Japanese Orthopaedic Association scoring system between the two groups. However, the PD group showed a higher proportion of non-ambulators and dependent ambulators with walkers at the final follow-up (p < 0.01). CONCLUSIONS: A similar surgical strategy can be applicable to patients with PD with OVF in the thoracolumbar junction. However, physicians should pay extra attention to intensive perioperative care to prevent various adverse events and implement a rehabilitation regimen to regain walking ability.

Surgical outcomes of spinal fusion for osteoporotic vertebral fracture in the thoracolumbar spine: Comprehensive evaluations of 5 typical surgical fusion techniques.

BACKGROUND: A consensus on the optimal surgical procedure for thoracolumbar OVF has yet to be reached due to the previous relatively small number of case series. The study was conducted to investigate surgical outcomes for osteoporotic vertebral fracture (OVF) in the thoracolumbar spine. METHODS: In total, 315 OVF patients (mean age, 74 years; 68 men and 247 women) with neurological symptoms who underwent spinal fusion with a minimum 2-year follow-up were included. The patients were divided into 5 groups by procedure: anterior spinal fusion alone (ASF group, n = 19), anterior/posterior combined fusion (APSF group, n = 27), posterior spinal fusion alone (PSF group, n = 40), PSF with 3-column osteotomy (3CO group, n = 92), and PSF with vertebroplasty (VP + PSF group, n = 137). RESULTS: Mean operation time was longer in the APSF group (p < 0.05), and intraoperative blood loss was lower in the VP + PSF group (p < 0.05). The amount of local kyphosis correction was greater in the APSF and 3CO groups (p < 0.05). Clinical outcomes were approximately equivalent among all groups. CONCLUSION: All 5 procedures resulted in acceptable neurological outcomes and functional improvement in walking ability. Moreover, they were similar with regard to complication rates, prevalence of mechanical failure related to the instrumentation, and subsequent vertebral fracture. Individual surgical techniques can be adapted to suit patient condition or severity of OVF.

Total spondylectomy for Enneking stage III giant cell tumor of the mobile spine.

PURPOSE: We reported the surgical outcomes of total en bloc spondylectomy (TES) with intralesional T-saw transpedicular osteotomy in patients with Enneking stage III spinal giant cell tumors (GCTs). METHODS: The medical records and imaging and pathological studies of 25 consecutive patients with Enneking stage III spinal GCTs undergoing surgery at our institution who were followed for at least 2 years were retrospectively reviewed. RESULTS: Eight men and 17 women (mean age: 34.2 years, range 16-51 years, at the time of surgery) were included. Six patients underwent previous tumor excision at another hospital, and one patient had a history of denosumab treatment. The GCTs were at the cervical, thoracic, and lumbar levels in three, nine, and 13 patients, respectively. TES was performed in 13 patients; 12 required intralesional pediculotomy. The remaining patients underwent total piecemeal spondylectomy with further intralesional tumor resection. During a mean follow-up of 99.2 months (range 24-216), two patients who underwent total piecemeal spondylectomy had local tumor recurrence, but no patients who underwent TES with intralesional pediculotomy had recurrence. The 2- and 10-year recurrence-free survival rates of patients treated with total piecemeal spondylectomy were 91.7% and 78.6%, respectively, while those of patients treated with TES were both 100%. CONCLUSIONS: TES with intralesional pediculotomy had a good surgical outcome even in patients with Enneking stage III spinal GCT, suggesting that minimal intralesional procedures could radically cure spinal GCTs. These slides can be retrieved under Electronic Supplementary Material.

Risk factors for local recurrence after total en bloc spondylectomy for metastatic spinal tumors: A retrospective study.

BACKGROUND: The aim of this study was to evaluate local recurrence and survival outcomes after frozen autograft total en bloc spondylectomy for metastatic spinal tumors. METHODS: We retrospectively analyzed data from 91 patients with metastatic spinal tumors who underwent frozen autograft total en bloc spondylectomy at our institution between May 2010 and April 2015. We assessed the incidence, primary cancer type, and sites of local recurrence. Risk factors for local recurrence were also examined through the statistical analysis of 17 items, including clinico-pathological characteristics, treatment history, and preoperative or surgical complications. Survival outcomes were evaluated with particular attention paid to the presence of local recurrence. RESULTS: The median follow-up duration was 27.4 months (range, 4-66 months). Local recurrence was diagnosed in 10 of 91 patients (11.0%). The sites of recurrence were intradural in 4 cases, epidural in 3 cases, in a vertebral body adjacent to the resected vertebral body in 2 cases, and in the paraspinal muscle in 3 cases. None of the patients had recurrence from the liquid nitrogen-treated tumor-bearing autograft. There were no local recurrences of renal cell carcinoma, thyroid cancer, or lung cancer. Multivariate analysis indicated that radiotherapy history was the only risk factor for local recurrence (odds ratio, 6.26; 95% confidence interval, 1.21-45.62; p = 0.04). The 2-year survival rate was significantly lower for the recurrence group than for the non-recurrence group (p < 0.05). CONCLUSIONS: A history of radiation was the only risk factor for local recurrence. Patients with recurrence had a significantly worse prognosis than those without recurrence.

Spinal metastasectomy of renal cell carcinoma: A 16-year single center experience with a minimum 3-year follow-up.

BACKGROUND AND OBJECTIVES: Metastasectomy of spinal lesions from renal cell carcinoma (RCC) is a promising strategy. However, its clinical outcome after spinal metastasectomy is unknown owing to the difficulty of curative surgical resection. This is the first study to examine the survival rates of patients who underwent metastasectomy of solitary spinal metastases from RCC. METHODS: A retrospective cohort study of 36 consecutive patients with RCC who underwent nephrectomy and complete removal of solitary spinal lesions between 1995 and 2010 at our institution. Cancer-specific survival (CSS) time from the spinal metastasectomy to death or last follow-up was the main endpoint. Potential factors associated with survival were evaluated with Kaplan-Meier analysis and the long-rank test. RESULTS: For all patients, the estimated median CSS time was 130 months. The 3, 5, and 10-year CSS rates were 77.8%, 69.1%, and 58.0%, respectively, for all patients, and 72.7%, 54.5%, and 27.3%, respectively, for patients with lung metastases at the time of surgery. Only the presence of liver metastases was significantly associated with short-term survival after spinal metastasectomy. CONCLUSIONS: Liver metastases were associated with short-term survival, although lung metastases were not. For selected patients, curative resection of solitary spinal metastases can potentially prolong survival. J. Surg. Oncol. 2016;113:587-592. © 2016 Wiley Periodicals, Inc.

Repeated total en bloc spondylectomy for spinal metastases at different sites in one patient.

PURPOSE: Total en bloc spondylectomy (TES) is accompanied by preoperative embolization of segmental arteries, which is limited to three consecutive levels to avoid the risk of spinal cord ischemia. We retrospectively examined the efficacy and safety of repeated TES with embolization of more than three levels of segmental arteries. METHODS: Seven patients underwent TES twice for spinal metastases at different levels. Every patient underwent embolization of the bilateral segmental arteries before each surgery. We assessed the total number of segmental arteries embolized, the existence of Adamkiewicz arteries during the embolization procedure, intraoperative blood loss, and the motor function of the lower limbs, using the American Spinal Injury Association (ASIA) motor score. RESULTS: No patient experienced any motor deficit after embolization. During the embolization procedure, an Adamkiewicz artery was depicted in five patients, which precluded embolization at that level. The median number of segmental arteries embolized in total was 9 (9-11). Intraoperative blood loss (median, IQR) was 480 (420-630) ml during the first surgery and 520 (280-600) ml during the second surgery. The ASIA motor scores (median, IQR) were as follows; 100 (98-100) (first admission), 100 (100-100) (first discharge), 100 (98-100) (second admission), and 97 (94-100) (second discharge). No patients had developed statistically significant neurological deterioration, and there had been no local recurrence after a median follow-up of 17.8 months (range 1-51 months). CONCLUSION: Repeated TES procedures can be performed safely even if more than three levels of segmental arteries are embolized.

[Motion Analysis of Lumbar Spine and Hip Joint on Sequential Radiographs Acquired with a Dynamic Flat-panel Detector (FPD) System].

PURPOSE: To design an evaluation method for lumbar spine and hip joint function using dynamic radiography using a flat-panel detector (FPD) system. METHOD: Sixteen healthy subjects (males; age range, 22-60 years; median, 27 years) and 9 patients (7 males and 2 females; age range, 67-85 years; median, 73 years) with L4 degenerative spondylolisthesis were examined using a dynamic FPD system (CANON Inc.). Sequential images were captured with the subjects in the standing position with maximal forward bending followed by backward bending for 10 s. The lateral lumbar radiographs were obtained at 2 frames/s (fps). The flexion-extension angles of L1 and S1 were measured on those images. RESULTS AND DISCUSSION: The range of motion (ROM) of the lumbar joints was significantly larger in the healthy group (82.4 ± 8.7°) than in the disease group (50.4 ± 8.5°; p<0.05). The ROM of the pelvic region was significantly smaller in the healthy group (26.9 ± 17.1°) than in the disease group (53.1 ± 17.6°; p<0.05). The healthy subjects exhibited a normal lumbar-pelvic rhythm. In the disease group, hip joint movements tended to be completed earlier compared with those in the healthy group. In the disease group, the loss of lumbar flexibility was compensated by an increase in hip joint motion due to the lumbar disease. CONCLUSION: The dynamic FPD system is a convenient imaging modality for the diagnosis of lumbar diseases through the assessment of locomotive function in the lumbar spine and hip joints.

More than 10-year follow-up after total en bloc spondylectomy for spinal tumors.

BACKGROUND: There are many reports of en bloc resection for spinal tumors. However, no studies have evaluated the clinical outcomes with follow-up exceeding 10 years after surgery. METHODS: We reviewed 82 patients who had undergone total en bloc spondylectomy (TES) before January 2002 and identified 29 (19 with primary tumors and 10 with metastatic tumors) who had survived for more than 10 years after surgery. We evaluated the clinical outcomes including patient-based outcomes using questionnaire. The questionnaire included subjective assessment of the results of TES and SF-36. RESULTS: Overall, 33 % of patients with metastases from kidney cancer and 25 % of those with metastases from thyroid cancer survived for more than 10 years after TES for solitary spinal metastases. Four patients with metastatic tumors had no evidence of disease at the time of survey. There were no tumor recurrences in any of the 23 patients who underwent TES as the primary surgery. No revision surgeries have been required as a result of instrumentation failure in any of the 29 patients. About 90 % of the patients were satisfied or very satisfied with the results of TES. The SF-36 results demonstrated that the both physical and mental health of patients with primary tumors was equivalent to those of healthy individuals, and the mental health of patients with metastatic tumors was almost similar to them. CONCLUSIONS: This study showed the long-term clinical outcomes after TES to be favorable. TES played an important role in the treatment strategy for spinal tumors including metastases.

Characterization of a unique motif in LIM mineralization protein-1 that interacts with jun activation-domain-binding protein 1.

Development and repair of the skeletal system and other organs are highly dependent on precise regulation of the bone morphogenetic protein (BMP) pathway. The use of BMPs clinically to induce bone formation has been limited in part by the requirement of much higher doses of recombinant proteins in primates than were needed in cell culture or rodents. Therefore, increasing cellular responsiveness to BMPs has become our focus. We determined that an osteogenic LIM mineralization protein, LMP-1 interacts with Smurf1 (Smad ubiquitin regulatory factor 1) and prevents ubiquitination of Smads resulting in potentiation of BMP activity. In the region of LMP-1 responsible for bone formation, there is a motif that directly interacts with the Smurf1 WW2 domain and thus effectively competes for binding with Smad1 and Smad5, key signaling proteins in the BMP pathway. Here we show that the same region also contains a motif that interacts with Jun activation-domain-binding protein 1 (Jab1) which targets a common Smad, Smad4, shared by both the BMP and transforming growth factor-ß (TGF-ß) pathways, for proteasomal degradation. Jab1 was first identified as a coactivator of the transcription factor c-Jun. Jab1 binds to Smad4, Smad5, and Smad7, key intracellular signaling molecules of the TGF-ß superfamily, and causes ubiquitination and/or degradation of these Smads. We confirmed a direct interaction of Jab1 with LMP-1 using recombinantly expressed wild-type and mutant proteins in slot-blot-binding assays. We hypothesized that LMP-1 binding to Jab1 prevents the binding and subsequent degradation of these Smads causing increased accumulation of osteogenic Smads in cells. We identified a sequence motif in LMP-1 that was predicted to interact with Jab1 based on the MAME/MAST sequence analysis of several cellular signaling molecules that are known to interact with Jab-1. We further mutated the potential key interacting residues in LMP-1 and showed loss of binding to Jab1 in binding assays in vitro. The activities of various wild-type and mutant LMP-1 proteins were evaluated using a BMP-responsive luciferase reporter and alkaline phosphatase assay in mouse myoblastic cells that were differentiated toward the osteoblastic phenotype. Finally, to strengthen physiological relevance of LMP-1 and Jab1 interaction, we showed that overexpression of LMP-1 caused nuclear accumulation of Smad4 upon BMP treatment which is reflective of increased Smad signaling in cells.

Pedicle screws can be 4 times stronger than lateral mass screws for insertion in the midcervical spine: a biomechanical study on strength of fixation.

STUDY DESIGN: A biomechanical study. OBJECTIVE: To compare, in cervical vertebrae (C3-C6), the pullout strengths of pedicle screws and lateral mass screws after both types of screw had been subjected to a period of cyclic loading in 2 planes. SUMMARY OF BACKGROUND DATA: In posterior subaxial cervical fixation systems, screws are usually inserted into the lateral mass. As an alternative to lateral mass fixation, pedicle screw fixation became popular in the 1990s and was first used for lower cervical spine trauma cases. However, it is controversial as to whether lateral mass screw fixation in the upper-middle cervical spine offers as much biomechanical security as compared with pedicle screw fixation. METHODS: For each of the 32 vertebrae, 1 side was randomly chosen to receive a pedicle screw and the other side a lateral mass screw. The pedicle or lateral mass screws inserted into the first 16 vertebrae were cyclically loaded to simulate torsion and the remaining 16 vertebrae were cyclically loaded to simulate flexion/extension of the spine. At the end of the cyclic loading each screw was pulled out along its long axis. RESULTS: For the torsion group, the mean pullout strength of the pedicle screws was nearly 4 times greater than the mean pullout strength of the lateral mass screws (cf 762 N with 191 N). In contrast, the mean pullout strength of the pedicle screws in the flexion/extension group was only twice the mean pullout strength of the lateral mass screws (cf 571 N with 289 N). CONCLUSIONS: Not forgetting the potential risks of inserting pedicle screws in cervical vertebrae, pedicle screws are a better biomechanical choice than lateral mass screws for cervical fixation at the levels C3 through to C6.

Characteristics and risk factors of instrumentation failure following total en bloc spondylectomy.

AIMS: The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF. METHODS: The medical records from 136 patients (65 male, 71 female) with a mean age of 52.7 years (14 to 80) who underwent TES were retrospectively reviewed. The mean follow-up period was 101 months (36 to 232). Analyzed factors included incidence of IF, age, sex, BMI, history of chemotherapy or radiotherapy, tumour histology (primary or metastasis; benign or malignant), surgical approach (posterior or combined), tumour location (thoracic or lumbar; junctional or non-junctional), number of resected vertebrae (single or multilevel), anterior resection line (disc-to-disc or intravertebra), type of bone graft (autograft or frozen autograft), cage subsidence (CS), and local alignment (LA). A survival analysis of the instrumentation was performed, and relationships between IF and other factors were investigated using the Cox regression model. RESULTS: A total of 44 patients (32.4%) developed IF at a median of 31 months (interquartile range 23 to 74) following TES. Most IFs were rod fractures preceded by a mean CS of 6.1 mm (2 to 18) and LA kyphotic enhancement of 10.8° (-1 to 36). IF-free survival rates were 75.8% at five years and 56.9% at ten years. The interval from TES to IF peaked at two to three years postoperatively and continued to occur over a period of time thereafter; the early IF-developing group had greater CS at one month postoperatively (CS1M) and more lumbar TES. CS1M ≥ 3 mm and sole use of frozen autografts were identified as independent risk factors for IF. CONCLUSION: IF is a common complication following TES. We have demonstrated that robust spinal reconstruction preventing CS, and high-quality bone grafting are necessary for successful reconstruction.Cite this article: Bone Joint J 2023;105-B(2):172-179.