Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification.

Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is crucial for the longitudinal growth and development of long bones, but what triggers the process is unknown. Reactive oxygen species (ROS) have been implicated in cellular damage; however, the physiological role of ROS in chondrogenesis is not well characterized. We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. Elevated ROS levels are detected in hypertrophic chondrocytes. In vivo and in vitro treatment with N-acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. In ataxia telangiectasia mutated (Atm)-deficient (Atm(-/-)) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. Decreased proliferation and excessive hypertrophy in Atm(-/-) mice were also rescued by antioxidant treatment. These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes.

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.

Morphometric analysis of the lumbar intervertebral foramen in patients with degenerative lumbar scoliosis by multidetector-row computed tomography.

PURPOSE: How the lumbar neural foramina are affected by segmental deformities in patients in whom degenerative lumbar scoliosis (DLS) is unknown. Here, we used multidetector-row computed tomography (MDCT) to measure the morphology of the foramina in three dimensions, which allowed us to elucidate the relationships between foraminal morphology and segmental deformities in DLS. METHODS: In 77 DLS patients (mean age, 69.4) and 19 controls (mean age, 69), the foraminal height (FH), foraminal width (FW), posterior disc height (PDH), interval between the pedicle and superior articular process (P-SAP), and cross-sectional foraminal area (FA) were measured on reconstructed MDCT data, using image-editing software, at the entrance, minimum-area point, and exit of each foramen. The parameters of segmental deformity included the intervertebral wedging angle and anteroposterior and lateral translation rate, measured on radiographs, and the vertebral rotation angle, measured using reconstructed MDCT images. RESULTS: The FH, PDH, P-SAP, and FA were smaller at lower lumbar levels and on the concave side of intervertebral wedging (p < 0.05). In the DLS patients, the FH, P-SAP, and FA were significantly smaller than for the control group at all three foraminal locations and every lumbar level (p < 0.05). Intervertebral wedging strongly decreased the FA of the concave side (p < 0.05). Anteroposterior translation caused the greatest reduction in P-SAP (p < 0.05). Vertebral rotation decreased the P-SAP and FA at the minimum-area point on the same side as the rotation (p < 0.05). CONCLUSION: The new analysis method proposed here is useful for understanding the pathomechanisms of foraminal stenosis in DLS patients.

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.

Ectodomain shedding of FLT3 ligand is mediated by TNF-alpha converting enzyme.

FLT3 ligand (FLT3L) has diverse roles in the hematopoietic system, which include stimulating proliferation of hematopoietic precursors and development of NK cells and dendritic cells. FLT3L is initially synthesized as a membrane-bound protein, which must be cleaved to become a soluble growth factor. However, little is known about the enzyme involved in the proteolytic release of FLT3L. In the current study, we show that shedding of FLT3L is metalloprotease-dependent, and that this proteolytic activity was abolished in fibroblasts lacking TNF-alpha converting enzyme (TACE) and could be rescued by reintroducing wild-type TACE in these cells. Moreover, we found that cells derived from the thymus of conditional TACE-deficient mice produce less FLT3L, and that serum FLT3L levels in these TACE mutant mice are significantly lower, both after LPS treatment and in the absence of such a challenge, further corroborating the relevance of TACE as FLT3L sheddase in vivo. Considering the involvements of FLT3 and FLT3L in hematopoietic malignancies and stem cell mobilization, the identification of the enzyme involved in FLT3L shedding may have important clinical implications.

Conditional inactivation of TACE by a Sox9 promoter leads to osteoporosis and increased granulopoiesis via dysregulation of IL-17 and G-CSF.

The TNF-alpha converting enzyme (TACE/ADAM17) is involved in the proteolytic release of the ectodomain of diverse cell surface proteins with critical roles in development, immunity, and hematopoiesis. As the perinatal lethality of TACE-deficient mice has prevented an analysis of the roles of TACE in adult animals, we generated mice in which floxed Tace alleles were deleted by Cre recombinase driven by a Sox9 promoter. These mutant mice survived up to 9-10 mo, but exhibited severe growth retardation as well as skin defects and infertility. The analysis of the skeletal system revealed shorter long bones and prominent bone loss, characterized by an increase in osteoclast and osteoblast activity. In addition, these mice exhibited hypercellularity in the bone marrow and extramedullary hematopoiesis in the spleen and liver. Flow cytometric analysis of the bone marrow cells showed a sharp increase in granulopoiesis and in the population of c-Kit-1(+) Sca-1(+) lineage(-) cells, and a decrease in lymphopoiesis. Moreover, we found that serum levels of IL-17 and G-CSF were significantly elevated compared with control littermates. These findings indicate that TACE is associated with a regulation of IL-17 and G-CSF expression in vivo, and that the dysregulation in G-CSF production is causally related to both the osteoporosis-like phenotype and the defects in the hematopoietic system.

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.

MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing.

Matrix metalloproteinases (MMPs) have been implicated in wound healing. To analyze the roles of MMP-9 and MMP-13 in wound healing, we generated full-thickness cutaneous wounds in MMP-9 knockout (KO), MMP-13 KO, MMP-9/13 double KO, and wild-type mice. Macroscopic wound closure was delayed in all of the KO mice, as compared with wild-type mice. The rate of re-epithelialization was significantly delayed in MMP-9 KO and MMP-13 KO mice and remarkably delayed in MMP-9/13 double KO mice, as compared with wild-type mice. Both MMP-9 and MMP-13 were expressed by the leading edges of epidermal cells in wild-type mice, and the migration of keratinocytes was suppressed by treatment with an MMP inhibitor or transfection of small interfering RNAs for MMP-9 or MMP-13, as compared with controls. The vascular density in wound granulation was significantly lower in both MMP-13 KO and MMP-9/13 double KO mice than in wild-type mice. Degradation of connective tissue growth factor in wound tissue was transiently prevented in MMP-13 KO mice. Morphometric analyses demonstrated a reduction in both wound contraction and myofibroblast formation in both MMP-13 KO and MMP-9/13 double KO mice. Proliferation and transforming growth factor-beta1-induced myofibroblast differentiation of dermal fibroblasts from MMP-13 KO mice were decreased, as compared with wild-type dermal fibroblasts. These data suggest that MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in wound healing, while MMP-9 functions in keratinocyte migration.

Absence of gelatinase (MMP-9) or collagenase (MMP-13) attenuates adriamycin-induced albuminuria and glomerulosclerosis.

BACKGROUND/AIMS: The role of matrix metalloproteinases (MMPs) in the pathogenesis of glomerular injury appears to be complex. To investigate the role of individual MMPs, we examined the course of Adriamycin-induced albuminuria and glomerulosclerosis in mice lacking either a gelatinase (MMP-9) or a collagenase (MMP-13). METHODS: Adriamycin was administered to MMP-9 or MMP-13 knockout (KO) mice. Glomerular injury was assessed by the quantification of albuminuria, the glomerular injury score and type IV collagen immunostaining. RESULTS: Treatment of mice with Adriamycin (18 mg/kg i.v.) resulted in marked albuminuria and glomerulosclerosis reaching a peak at 4-8 weeks. The albuminuria and glomerulosclerosis were significantly (p < 0.05) attenuated in both the MMP-9 KO and MMP-13 KO mice compared to controls. In contrast, treatment of wild-type mice with the broad-spectrum MMP inhibitor doxycycline did not have a beneficial effect on the albuminuria and glomerulosclerosis. CONCLUSION: These results support a role for both gelatinase (MMP-9) and collagenase (MMP-13) in the pathogenesis of glomerular injury in the Adriamycin-induced glomerulosclerosis model. MMP inhibitors with high specificity towards MMP-9 and/or MMP-13 may be potential future candidates to provide more effective therapies to inhibit the development of glomerulosclerosis.

1-Alpha, 25-dihydroxy vitamin D3 inhibits osteoclastogenesis through IFN-beta-dependent NFATc1 suppression.

1-Alpha, 25-dihydroxy vitamin D(3) (1alpha,25(OH)(2)D(3)), an active form of vitamin D(3), plays a critical role in calcium and bone metabolism. Although 1alpha,25(OH)(2)D(3) has been used for osteoporosis therapy, the direct role of 1alpha,25(OH)(2)D(3) on human osteoclastogenesis has not been well characterized. Here we show that 1alpha,25(OH)(2)D(3) treatment significantly inhibited human osteoclast formation at the early stage of differentiation in a concentration-dependent manner. 1alpha,25(OH)(2)D(3) inhibited the expression of nuclear factor of activated T cells c1 (NFATc1, also referred as NFAT2), an essential transcription factor for osteoclast differentiation, and upregulated the expression of interferon-beta (IFN-beta), a strong inhibitor of osteoclastogenesis in osteoclast progenitors. Inhibitory effects of 1alpha,25(OH)(2)D(3) on osteoclastogenesis and NFATc1 expression were restored by treatment with an antibody against IFN-beta, suggesting that upregulation of IFN-beta by 1alpha,25(OH)(2)D(3) treatment results in inhibition of NFATc1 expression, in turn interfering with osteoclast formation. Thus, our study may provide a molecular basis for the treatment of human bone diseases by 1alpha,25(OH)(2)D(3) through regulation of the IFN-beta and NFATc1 axis.

[Updates on ossification of posterior longitudinal ligament. Bone metabolism in ossification of posterior longitudinal ligament].

Ossification of the longitudinal ligament in the spine is a disorder of unknown cause characterized by ectopic ossification. In the animal models of spinal hyperostosis, the vertebral ligament is gradually replaced by bony tissue forming an osseous bridge around enthesis, and a high turnover osteopenia occurs after the maturation in the trabecular bone of vertebrae. It has been suggested that the recruited vasculature facilitated the filling of the niche with host-derived haematopoietic cells during the ectopic ossification process. Recent data suggest that regulation of hematopoietic and osteogenic stem/progenitor cell populations may contribute to the formation of an ectopic spinal hyperostosis.

Risk factors for closure of lamina after open-door laminoplasty.

OBJECT: This retrospective study was conducted to evaluate the prevalence and clinical consequences of postoperative lamina closure after open-door laminoplasty and to identify the risk factors. METHODS: Eighty-two consecutive patients with cervical myelopathy who underwent open-door laminoplasty without plates or spacers in the open side (Hirabayashi's original method) were included (62 men and 20 women with a mean age of 62 years and a mean follow-up of 1.8 years). In 67 patients the cause of cervical myelopathy was spondylotic myelopathy, and in 15 it was caused by ossification of posterior longitudinal ligament. Radiographic measurements were made of the anteroposterior diameters of the spinal canal and vertebral bodies from C3-6, and the presence of kyphosis were assessed. Lamina closure was defined as > or = 10% decrease in the canal-to-body ratio at the final follow-up compared with that immediately after surgery at > or = 1 vertebral level. The impact of lamina closure on neck pain, patient satisfaction, Japanese Orthopaedic Association scores, and recovery rates were also evaluated. RESULTS: The mean canal-to-body ratio at C3-6 was 0.69-0.72 preoperatively, 1.25-1.28 immediately after surgery, and 1.18-1.24 at the final follow-up examination. Lamina closure was observed in 34% of patients and was not associated with sex, age, or cause of myelopathy, but was significantly associated with the presence of preoperative kyphosis (p = 0.014). Between patients with and without lamina closure, there was no significant difference in preoperative (9.7 +/- 3.1 vs 10.6 +/- 2.5) and postoperative (13.7 +/- 2.4 vs 13.1 +/- 2.7) Japanese Orthopaedic Association scores, recovery rates (53.9 +/- 29.9% vs 44.3 +/- 29.5%), neck pain scores (3.5 +/- 0.7 vs 3.3 +/- 1.0), or patient satisfaction level (4.0 +/- 1.4 vs 4.8 +/- 1.0). CONCLUSIONS: Lamina closure at > or = 1 vertebral level occurred in 34% of patients. Although patients with lamina closure obtained equivalent recovery from myelopathy in a short-term follow-up, they tended to be less satisfied with surgery compared with those who did not have closure. The only significant risk factor identified was the presence of preoperative cervical kyphosis, and preventative methods for lamina closure, therefore, should be considered for patients with preoperative kyphosis.

Extensive total spondylectomy for recurrent giant cell tumor in the thoracic spine. Case report.

The authors report the case of a 47-year-old woman who harbored a giant cell tumor at the T-5 level. She had undergone curettage of the tumor via a combined anterior and posterior approach at a regional hospital and was later referred to the authors' institution for treatment after the tumor recurred. On examination she exhibited progressive paraparesis and was nonambulatory due to cord compression caused by the tumor, which had invaded the spinal canal and extended to the right paravertebral muscles and right thoracic cavity. A spondylectomy was performed through a single posterior approach. The tumor, together with a portion of the dura mater, pleura, and muscles, was resected en bloc from T-4 to T-6. After resection, spinal reconstruction was performed by placement of an anterior titanium mesh cage as well as posterior pedicle screw and rod instrumentation. The patient's postoperative course was uneventful, and she exhibited substantial neurological recovery and became ambulatory. Two and a half years after surgery, the patient was tumor free. En bloc resection of a recurrent giant cell tumor was successfully achieved through a single posterior approach. This surgical technique can be an effective option for this pathological condition, which is difficult to manage using other conventional treatment options including repeated curettage and radiotherapy.

Risk factors for intervertebral instability assessed by temporal evaluation of the radiographs and reconstructed computed tomography images after L5-S1 single-level transforaminal interbody fusion: A retrospective study.

Intervertebral instability risks following L5-S1 transforaminal lumbar interbody fusion (TLIF) and causes of bony bridge formation on computed tomography (CT) remain largely unknown. We evaluated the temporal changes on plain radiographs and reconstructed CT images from 178 patients who had undergone single-level L5-S1 TLIF between February 2011 and February 2015. We statistically analyzed temporal changes the L5-S1 angle on radiographs and intervertebral stability (IVS) at the last observation. Bony bridge formation between the L5-S1 vertebral bodies and the titanium cage subsidence were analyzed by using reconstructed CT. Preoperative L5-S1 angle in the non-IVS group was significantly greater than that in the IVS group. The cage subsidence was classified as follows: type A, both upper and lower endplates; type B, either endplate; or type C, no subsidence. Types B and C decreased over time, whereas type A increased after surgery. The bony bridges between vertebral bodies were found in 87.2% of patients, and 94.5% of all bony bridges were found only in the cage, not on the contralateral side. Our findings suggested that high preoperative L5-S1 angle increased the risk of intervertebral instability after TLIF. The L5-S1 angle decreased over time with increasing type A subsidence, and almost all bony bridges were found only in the cage. These results suggest that the vertebral bodies were stabilized because of cage subsidence, and final bony bridges were created. Methods to improve bony bridge creation are needed to obtain reliable L5-S1 intervertebral bone union.

Postoperative factors affecting neurological recovery after surgery for cervical spondylotic myelopathy.

OBJECT: Many prognostic factors associated with surgery for cervical spondylotic myelopathy (CSM) have been detailed in the literature. All of these factors, however, are defined preoperatively. If it is possible to clarify factors influencing surgical results that can be modulated after surgery, then the overall results of surgery may improve. The purpose of this study was to elucidate such postoperative factors affecting neurological recovery. METHODS: The authors assessed the surgical outcomes obtained in 183 patients with CSM who underwent expansive open-door laminoplasty between 1993 and 2004 and who underwent follow up for a minimum of 1 year. They classified the cases into two groups according to the degree of neurological recovery: an excellent recovery group, comprising patients in whom the recovery rates were greater than 75%, and a poor recovery group, composed of patients in whom the recovery rates were lower than 30%. Comparisons of various clinical and imaging parameters revealed that the mean age at surgery was significantly lower in patients in the excellent recovery group than that in the poor recovery group. Therefore, the authors repeated the same analyses after adjustment for age. Postoperative cervical range of motion (ROM) was significantly more reduced in the excellent recovery group than in the poor recovery group. There was a significant positive correlation between reduced cervical ROM and recovery rate in the poor recovery group. CONCLUSIONS: Dynamic stress may ameliorate functional recovery of the degenerated spinal cord even after sufficient decompression. Postoperative preservation of cervical ROM may not always be beneficial for neurological recovery in patients with CSM.

Long-term results after expansive open-door laminoplasty for the segmental-type of ossification of the posterior longitudinal ligament of the cervical spine: a comparison with nonsegmental-type lesions.

OBJECT: The segmental-type of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine is distinct from other types in its morphological features. Whether the results of expansive open-door laminoplasty for the segmental-type are different from those for other types remains unclear. To clarify this issue, the long-term results after surgical treatment of segmental-type OPLL were compared with those of other types. METHODS: Clinical results were documented in 57 patients who underwent expansive open-door laminoplasty and were followed for a minimum of 7 years, results were quantified using the Japanese Orthopaedic Association (JOA) scoring system to determine function. Segmental-type OPLL was observed in 10 patients (Group 1) and other types in 47 patients (Group 2). Preoperative JOA scores were not significantly different between the two groups. As many as 5 years after surgery, clinical results were favorable and maintained in both groups, and no significant intergroup difference in postoperative JOA scores was observed; however, after 5 years postoperatively, JOA scores decreased in both groups. The decrease was greater in Group 1, and a significant intergroup difference in JOA scores was demonstrated when analyzing final follow-up data. In Group 1, the authors found that the degree of late-onset deterioration relating to cervical myelopathy positively correlated with the cervical range of motion. CONCLUSIONS: The long-term results of expansive open-door laminoplasty in the treatment of segmental-type OPLL were inferior to those for other types. Cervical mobility may contribute to the development of late deterioration of cervical myelopathy.

Long-term results of expansive open-door laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine.

OBJECT: Numerous surgical procedures have been developed for treatment of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine, and these can be performed via three approaches: anterior, posterior, or combined anterior-posterior. The optimal approach in cases involving OPLL-induced cervical myelopathy, however, remains controversial. To address this issue, the authors assessed the benefits and limitations of expansive open-door laminoplasty for OPLL-related myelopathy by evaluating mid- and long-term clinical results. METHODS: Clinical results obtained in 72 patients who underwent expansive open-door laminoplasty between 1983 and 1997 and who were followed for at least 5 years were assessed using the Japanese Orthopaedic Association (JOA) scoring system. The mean preoperative JOA score was 9.2 +/- 0.4; at 3 years postoperatively, the JOA score was 14.2 +/- 0.3 and the recovery rate (calculated using the Hirabayashi method) was 63.1 +/- 4.5%, both having reached their highest level. These favorable results were maintained up to 5 years after surgery. An increase in cervical myelopathy due to progression of the ossified ligament was observed in only two of 30 patients who could be followed for more than 10 years. Severe surgery-related complications were not observed. Preoperative JOA score, age at the time of surgery, and duration between onset of initial symptoms and surgery affected clinical results. CONCLUSIONS: Mid-term and long-term results of expansive open-door laminoplasty were satisfactory. Considering factors that affected surgical results, early surgery is recommended for OPLL of the cervical spine.

Remodeling of C2 facet deformity prevents recurrent subluxation in patients with chronic atlantoaxial rotatory fixation: a novel strategy for treatment of chronic atlantoaxial rotatory fixation.

STUDY DESIGN: A retrospective case series. OBJECTIVE: To propose a novel treatment strategy for chronic atlantoaxial rotatory fixation (AARF). SUMMARY OF BACKGROUND DATA: Treatment strategy for chronic or recurrent AARF remains controversial. We have previously reported that a deformity of the superior facet of the axis (C2 facet deformity), which is frequently observed in patients with chronic AARFs, is a risk factor for recurrent dislocation. In this article, we report seven consecutive cases of chronic AARF who underwent closed manipulation followed by external halo fixation and maintained good reduction with the remodeling of the C2 facet deformity. METHODS: Seven girls with a chronic AARF who sustained torticollis for an average of 4.6 months after the onset were referred to our clinic. Closed manipulation by careful manipulation under general anesthesia followed by external immobilization with a halo vest was performed in all cases. Radiographic findings and clinical courses were retrospectively reviewed with approvals by the institutional review board. RESULTS: Three-dimensional computed tomography images before reduction revealed persistent atlantoaxial subluxation and the C2 facet deformity in the dislocated side in all cases. Follow-up three-dimensional computed tomographic scans demonstrated the remodeling of the C2 facet deformity at an average of 2.8 months after successful reduction of subluxation. Subsequently, the halo vests were removed and gentle neck range of motion exercise was started in all cases. The normal cervical range of motion was obtained 2 weeks after the removal of halo vests in five cases, whereas the range of motion remained limited in two cases. At a mean follow-up of 17.4 months, neither symptoms nor recurrence of subluxation occurred in all cases. CONCLUSION: Chronic irreducible and recurrent unstable AARF can be managed successfully by careful closed manipulation followed by halo fixation, if the C1 and C2 have not been osseously fused. The remodeling of the C2 facet deformity detected on follow-up CT scans can be a useful radiographic parameter to determine the appropriate period of halo fixation in this new treatment strategy obviating the need for surgical intervention.

Reduced postoperative wound pain after lumbar spinous process-splitting laminectomy for lumbar canal stenosis: a randomized controlled study.

OBJECT: to reduce intraoperative damage to the posterior supporting structures of the lumbar spine during decompressive surgery for lumbar canal stenosis (LCS), lumbar spinous process-splitting laminectomy (LSPSL or split laminectomy) was developed. This prospective, randomized, controlled study was conducted to clarify whether the split laminectomy decreases acute postoperative wound pain compared with conventional laminectomy. METHODS: forty-one patients with LCS were enrolled in this study. The patients were randomly assigned to either the LSPSL group (22 patients) or the conventional laminectomy group (19 patients). Questionnaires regarding wound pain (intensity, depth, and duration) and activities of daily living (ADL) were administered at postoperative days (PODs) 3 and 7. Additionally, the authors evaluated the pre- and postoperative serum levels of C-reactive protein and creatine phosphokinase, the amount of pain analgesics used during a 3-day postoperative period, and the muscle atrophy rate measured on 1-month postsurgical MR images. RESULTS: data obtained in patients in the LSPSL group and in 16 patients in the conventional laminectomy group were analyzed. The mean visual analog scale for wound pain on POD 7 was significantly lower in the LSPSL group (16 ± 17 mm vs 34 ± 31 mm, respectively; p = 0.04). The mean depth-of-pain scores on POD 7 were significantly lower in the LSPSL group than in the conventional group (0.9 ± 0.6 vs 1.7 ± 0.8, respectively; p = 0.013). On POD 3, the mean serum creatine phosphokinase level was significantly lower in the LSPSL group (126 ± 93 U/L) than in the other group (207 ± 150 U/L) (p = 0.02); on POD 7, the mean serum C-reactive protein level was significantly lower in the LSPSL group (1.1 ± 0.6 mg/dl) than in the conventional laminectomy group (1.9 ± 1.5 mg/dl) (p = 0.04). The number of pain analgesics taken during the 3-day postoperative period was lower in the LSPSL group than in the conventional laminectomy group (1.7 ± 1.3 tablets vs 2.3 ± 2.4 tablets, respectively; p = 0.22). The mean muscle atrophy rate was also significantly lower in the LSPSL group (24% ± 15% vs 43% ± 22%; p = 0.004). CONCLUSIONS: lumbar spinous process-splitting laminectomy for the treatment of LCS reduced acute postoperative wound pain and prevented postoperative muscle atrophy compared with conventional laminectomy, possibly because of minimized damage to the paraspinal muscles.

Ball tip technique for thoracic pedicle screw placement in patients with adolescent idiopathic scoliosis.

OBJECT: The aim in this study was to evaluate the efficacy of the ball tip technique in placing thoracic pedicle screws (TPSs), as compared with the conventional freehand technique, in both a cadaveric study and a clinical study of patients with adolescent idiopathic scoliosis. Although posterior spinal surgery using TPSs has been widely applied, these screws are associated with the potential risk of vascular, pulmonary, or neurological complications. To further enhance the accuracy and safety of TPS placement, the authors developed the ball tip technique. METHODS: After creating an appropriate starting point for probe insertion, a specially designed ball tip probe consisting of a ball-shaped tip with a flexible metal shaft is used to make a guide hole into the pedicle. Holding the probe with the fingertips while using an appropriate amount of pressure or by tapping it gently and continuously with a hammer, one can safely insert the ball tip probe into the cancellous channel in the pedicle. In a cadaveric study, 5 spine fellows with similar levels of experience in placing TPSs applied the ball tip or the conventional technique to place screws in 5 cadavers with no spinal deformities. The incidence of misplaced screws was evaluated by dissecting the spines. In a clinical study, 40 patients with adolescent idiopathic scoliosis underwent posterior surgery with TPS placement via the ball tip or conventional technique (20 patients in each treatment group). The accuracy of the TPS placements was evaluated on postoperative axial CT scanning. RESULTS: In the cadaveric study, 100 TPSs were evaluated, and the incidence of misplaced screws was 14% in the ball tip group and 34% in the conventional group (p = 0.0192). In the clinical study, 574 TPSs were evaluated. One hundred seventy-one intrapedicular screws (67%) were recognized in the conventional group and 288 (90%) in the ball tip group (p < 0.01). In the conventional and ball tip groups, the respective numbers of TPSs with a pedicle breach of < or = 2 mm were 20 (8%) and 15 (5%), those with a pedicle breach of > 2 mm were 32 (13%) and 9 (3%; p < 0.01), and those located in the costovertebral joints were 32 (13%) and 7 (2%). CONCLUSIONS: In both cadaveric and clinical studies the ball tip technique enhanced the accuracy of TPS placement as compared with the conventional freehand technique. Thus, the ball tip technique is useful for the accurate and safe placement of TPSs in deformed spines.