Hodgkin's disease of the thoracic vertebrae.

BACKGROUND CONTEXT: Hodgkin's disease rarely occurs in the spine, which is usually a setting for the advanced form of the disease. PURPOSE: To describe an unusual case of isolated, primary spinal Hodgkin's disease and to draw attention to this disease as a possible diagnosis in patients with mixed inflammatory cell infiltrate lesions located in the thoracic spine. STUDY DESIGN/SETTING: A case report of a 28-year-old woman who presented with back pain and progressive weakness in the lower extremities as a result of spinal cord compression from Hodgkin's disease of the thoracic vertebrae. METHODS: We report a new case of spinal cord compression resulting from Hodgkin's disease of the thoracic vertebrae. Decompression surgery was performed in the patient, followed by antibiotic treatment. RESULTS: Antibiotic therapy temporarily improved inflammation and fever. However, magnetic resonance imaging (MRI) evaluation showed that the inflammatory reaction in the lesion was not completely resolved. The disease progressed and later investigations revealed Hodgkin's disease, which improved with a course of chemotherapy and radiation. CONCLUSIONS: Hodgkin's disease should be considered in the differential diagnosis of spinal neoplastic lesions with clinical features similar to spondylitis. Because MRI evaluation showed that the vertebral disc was maintained in this case, the presence of a tumor rather than inflammation should have been suspected.

Computer-assisted hemivertebral resection for congenital spinal deformity.

BACKGROUND: No studies have reported on osteotomies utilizing a navigation system in congenital scoliosis surgery. This study aimed to evaluate the surgical outcomes of eight patients with congenital scoliosis or kyphoscoliosis due to hemivertebrae treated by computer-assisted hemivertebral resection using only a posterior approach. METHODS: Eight consecutive patients (two scoliotics and six kyphoscoliotics) managed by computer-assisted hemivertebral resection using only a posterior approach with transpedicular instrumentation were investigated retrospectively. A CT-based navigation system was used to confirm the positions of the vertebra, spinal cord and aorta in real-time when we inserted a pedicle screw and conducted the osteotomy. The mean patient age at surgery was 18 years (range 11-41 years). The mean follow-up was 46 months (range 18-84 months). RESULTS: Before surgery, the mean kyphotic curve was 55.8° (range 26-83°), and the mean scoliotic curve was 50.0° (range 36-62°). At the final follow-up period, the curves averaged 23.2° (range 15-40°) and 31.6° (range 21-44°), respectively, yielding kyphotic angle corrections of 32.7° (range 11-58°) and Cobb angle correction rates of 36.8% (range 24.1-48.3%). A total of 72 pedicle screws were inserted with the navigation system, and two screws revealed a perforating pedicle. No neurovascular complications occurred. The perforation rate was 2.8%. CONCLUSIONS: Hemivertebral resection via a single posterior approach is less invasive than combined anterior and posterior approaches; however, this procedure increases the risk of spinal cord and vascular injuries. Computer-assisted hemivertebral resection enables safe and accurate performance of a hemivertebral resection via a single posterior approach.

Incidence of complications associated with spinal endoscopic surgery: nationwide survey in 2007 by the Committee on Spinal Endoscopic Surgical Skill Qualification of Japanese Orthopaedic Association.

BACKGROUND: This report was conducted to elucidate the current status of spinal endoscopic surgery and relevant incidents through analysis of the results of a questionnaire survey conducted in 2007 by the Committee on Spinal Endoscopic Surgical Skill Qualification of the Japanese Orthopaedic Association (JOA). METHODS: Questionnaire forms were sent to 2011 training facilities nationwide certified by the JOA, and 1082 of these facilities returned the filled questionnaires (response rate 53.8%). Of these facilities, 257 (23.8% of the responding facilities) undertook spinal endoscopic surgery in 2007. These institutions were asked to fill in the survey form with the details of the operations and relevant incidents as well as the incident levels. RESULTS: In total, the 257 facilities performed 6239 spinal endoscopic surgeries during 2007. Posterior spinal endoscopic surgery constituted most of the operations (6217 cases, 98.2%) including 4336 cases of microendoscopic discectomy (MED), 1273 cases of microendoscopic laminectomy or fenestration, and 379 cases of transforaminal or posterior lumbar interbody fusion. The total number of incidents was 133 (2.13%). The numbers of incidents by operative method were 75 (56.4%) during MED, 57 (42.9%) during microendoscopic laminectomy or fenestration, and 1 (0.8%) during interbody fusion. Of 133 incidents, dural tear occurred in 99 (74.4%), injury of the cauda equina or a nerve root in 7 (5.3%), facet fracture in 7 (5.3%), hematoma and wrong level in 6 each (4.5%), and wrong side and bedsore in 1 each (0.8%). The incident level was level 1 in 6, level 2 in 24, level 3a in 82, level 3b in 16, level 4 in 5, and level 5 (fatal) in 0. CONCLUSIONS: The results of this survey revealed an increasing trend of spinal endoscopic surgery and a decreasing trend of the complication rates. The complication rates of spinal endoscopic surgery were not higher than those of conventional surgery, indicating the safety of this surgical method.

Surgical resection without dural reconstruction of a lumbar meningioma in an elderly woman.

Meningiomas of the spine occur in the thoracic spine in approximately 80%, followed in frequency by the cervical and lumbar regions. The treatment of spinal meningiomas is complete surgical resection. As intraspinal meningiomas are almost always adherent to the dura, extensive dural resection or diathermic treatment of the dural attachment is usually performed to prevent tumor recurrence. The authors present the case of lumbar spinal meningioma in 82-year-old woman. Successful resection with preservation of the dura mater using the technique of Saito et al. (Spine 26:1805-1808, 2001) is described: After lumbar laminectomy a small incision was made in the surface of the spinal dura. The dura mater was separated into its inner and outer layers, and the tumor was resected with inner layer alone, preserving the outer layer. The outer layer is simply closed to achieve a watertight seal. The pathologic diagnosis was metaplastic (osseous) meningioma. Almost full recovery of the neurologic deficit was attained. Neither complication nor tumor recurrence has occurred in the 5 years since surgery. Dural preservation during surgical resection of spinal meningioma obviates the need for dural reconstruction and should reduce surgical morbidity. However, the patient should be followed long-term to watch for recurrence.

Characteristics of L3 nerve root radiculopathy.

BACKGROUND: In degenerative lumbar spinal disease with nerve root compression, the L5 and S1 nerve roots are the most often affected and the L3 nerve root is involved infrequently. The purpose of this study was to investigate the characteristics of L3 nerve root radiculopathy. METHODS: Seventeen consecutive patients with L3 radiculopathy were treated. The symptomatic nerve roots were determined by the pain distribution, the neurologic findings, and selective nerve root injection. The clinical characteristics and outcomes of these patients were assessed retrospectively. RESULTS: The average age was 76 years. The spinal diseases that were associated with L3 radiculopathy were lumbar canal stenosis in 6 patients, lumbar extraforaminal stenosis and lumbar disk herniation in 5 each, and lumbar canal stenosis with degenerative scoliosis in 1. The patients' symptoms were thigh pain in 12 patients, and hip or knee pain in 5. Four patients were nonambulatory because of severe pain. Although a sensory disturbance was reported in 9 patients, motor weakness was present in 2. Selective nerve root injection was completely effective in 10 patients. Six had decompressive surgery and/or fusion followed by a favorable outcome. Four patients were misdiagnosed and received conservative treatment for hip and/or knee joint diseases. CONCLUSIONS: L3 radiculopathy was characterized by various lower limb pain and neurologic deficit. Selective nerve root injection was effective for most patients. In elderly patients who do not respond to treatment for hip and/or knee joint diseases, L3 nerve root radiculopathy should be considered as the cause of lower limb pain.

Assessment of cervical myelopathy using transcranial magnetic stimulation and prediction of prognosis after laminoplasty.

STUDY DESIGN: This study investigated the clinical usefulness of motor-evoked potentials (MEPs) produced by transcranial magnetic stimulation of the brain for cervical myelopathy patients. OBJECTIVE: The purpose of this study was to determine the usefulness of MEPs for the assessment of the severity of myelopathy and prediction of the outcome of laminoplasty. SUMMARY OF BACKGROUND DATA: Magnetic stimulation has been widely used for examination of the descending excitatory motor pathways in the central nervous system, but little attention has been paid to cervical myelopathy. METHODS: We measured the MEPs of 56 patients who underwent surgery for cervical myelopathy. The MEPs from the abductor pollicis brevis, abductor digiti minimi, tibialis anterior, and abductor hallucis muscle were evoked by transcranial magnetic brain stimulation. The latency from the anterior horn cell of the spinal cord to the hand or foot muscles was also measured, with the F-value [(F + M - 1)/2] calculated. This was followed by estimation of the central motor conduction time (CMCT). Severity of clinical disability was scored on the basis of symptoms according to a modified ADL scale for cervical myelopathy of the Japanese Orthopedic Association (JOA) score. RESULTS: The average CMCT of the symptomatic side significantly correlated with the preoperative JOA score. The average CMCT of the symptomatic side significantly correlated with the 1-year postoperative JOA score. The average CMCT for patients with poor outcome was significantly longer than that for patients with good outcome. CMCT of 15 milliseconds or more in the upper extremities or that of 22 milliseconds or more in the lower extremities indicated poor prognosis. CONCLUSION: In patients with cervical myelopathy, the CMCT significantly correlated with the results of clinical assessment. These findings regarding the duration of CMCT may be useful parameters in spinal pathology for prediction of the outcome of surgical treatment.

Surgery for thoracic myelopathy caused by ossification of the ligamentum flavum.

BACKGROUND: Ossification of the ligamentum flavum overlying the lower thoracic spine frequently produces myelopathy. This study analyzed the postoperative outcomes after decompressive laminectomy for thoracic OLF. METHODS: We retrospectively studied 13 patients (10 male, 3 female; mean age, 58 years; range, 39-69). The mean follow-up duration was 66 months (range, 21-107). All patients had undergone decompressive laminectomy and excision of the OLF. The clinical course was evaluated according to the Frankel grading system and JOA scores. The number of vertebral segments demonstrating OLF, the most frequent level of thoracic cord involvement, and spine lesions coexisting with OLF were determined by MR imaging. RESULTS: By the Frankel system, 7 of 13 patients improved by one grade, whereas the others, classified as grade D, were unchanged after surgery. Using the JOA score, the functional improvement was excellent in 3 patients, good in 4, fair in 2, and unchanged in 4. The number of vertebral segments demonstrating OLF included 4 levels in 2 patients, 3 levels in 2 patients, 2 levels in 5 patients, and 1 level in 4 patients. Ossification of the ligamentum flavum occurred most frequently at the T10/T11 level. Tandem cervical and lumbar lesions were present in 6 patients. CONCLUSIONS: Decompressive laminectomy for excision of OLF resulted in clinical improvement using the Frankel grading system in 7 of 13 patients. In myelopathy patients with OLF, preoperative MR imaging of the entire spine is necessary because other coexisting spinal lesions may be present.

Computer-assisted screw insertion for cervical disorders in rheumatoid arthritis.

To reconstruct highly destructed unstable rheumatoid arthritis (RA) cervical lesions, the authors have been using C1/2 transarticular and cervical pedicle screw fixations. Pedicle screw fixation and C1/2 transarticular screw fixation are biomechanically superior to other fixation techniques for RA patients. However, due to severe spinal deformity and small anatomical size of the vertebra, including the lateral mass and pedicle, in the most RA cervical lesions, these screw fixation procedures are technically demanding and pose the potential risk of neurovascular injuries. The purpose of this study was to evaluate the accuracy and safety of cervical pedicle screw insertion to the deformed, fragile, and small RA spine lesions using computer-assisted image-guidance systems. A frameless, stereotactic image-guidance system that is CT-based, and optoelectronic was used for correct screw placement. A total of 21 patients (16 females, 5 males) with cervical disorders due to RA were surgically treated using the image-guidance system. Postoperative computerized tomography and plane X-ray was used to determine the accuracy of the screw placement. Neural and vascular complications associated with screw insertion and postoperative neural recovery were evaluated. Postoperative radiological evaluations revealed that only 1 (2.1%; C4) of 48 screws inserted into the cervical pedicle had perforated the vertebral artery canal more than 25% (critical breach). However, no neurovascular complications were observed. According to Ranawat's classification, 9 patients remained the same, and 12 patients showed improvement. Instrumentation failure, loss of reduction, or nonunion was not observed at the final follow-up (average 49.5 months; range 24-96 months). In this study, the authors demonstrated that image-guidance systems could be applied safely to the cervical lesions caused by RA. Image-guidance systems are useful tools in preoperative planning and in transarticular or transpedicular screw placement in the cervical spine of RA patients.

Posterior correction and fusion for severe cervical kyphosis in a patient with myotonic dystrophy: a case report.

STUDY DESIGN: A case report. OBJECTIVE: To report the first myotonic dystrophy case in which cervical kyphosis had been surgically corrected. SUMMARY OF BACKGROUND DATA: Myotonic dystrophy is an autosomal dominant disease that shows myotonia, progressive muscle atrophy, and other various symptoms. Instability of the neck is expected to cause disorders of the cervical spine; however, there are no detailed reports on deformity of cervical spine associated with this disease. METHODS: A 43-year-old man with cervical kyphosis due to myotonic dystrophy had undergone an occiput-T2 fusion with autogenous iliac bone using spinal instrumentation. RESULTS: The activity of daily life of the patient had improved markedly, and the good results continued to be preserved for 5 years. There were not any major perioperative complications. CONCLUSIONS: Surgical correction of cervical spine is not necessarily a contraindication for myotonic dystrophy.

Usefulness of white blood cell differential for early diagnosis of surgical wound infection following spinal instrumentation surgery.

STUDY DESIGN: The white blood cell (WBC) count and WBC differential were measured prospectively in patients after spinal instrumentation surgery with or without surgical wound infection. OBJECTIVES.: To investigate the usefulness of WBC differential for early diagnosis of surgical wound infection after spinal instrumentation surgery. SUMMARY OF BACKGROUND DATA: Renewed elevation of C-reactive protein (CRP) or WBC, gallium scan, and CRP/transthyretin mass concentration ratio were reported for early diagnosis of surgical wound infection. METHODS: A total of 39 patients were enrolled in this study: 13 patients who developed wound infection within 2 weeks after spinal instrumentation surgery (infection group) and 26 patients who were comparable with those patients included in the infection group with regard to age, sex, and surgical techniques used (control group). The WBC count and WBC differential were determined before and after surgery. RESULTS: In both groups, WBC and percentage and number of neutrophils showed nearly same change until postoperative 4 days (day 4). However, in the infection group, these parameters had increased after day 4. In both groups, the percentage and number of lymphocytes decreased to 10% or less and 1,000/microL or less on day 1, respectively. These lymphocyte parameters began to gradually normalize on day 4 and returned to the preoperative level 3 weeks after surgery in the control group. On the other hand, these parameters remained 10% or less and 1,000/muL or less until day 11 in the infection group. In patients with infection, the percentage and number of lymphocytes significantly decreased as early as on day 4. CONCLUSION: Lymphopenia represents immunodepression status, thus indicating the increased susceptibility to infection, which may lead to the development of postoperative infection. If lymphopenia is diagnosed as early as possible, surgical wound infection can be treated promptly without removing the instruments.

Magnetic resonance and computed tomography-based scoring system for the differential diagnosis of vertebral fractures caused by osteoporosis and malignant tumors.

BACKGROUND: Previous reports have described magnetic resonance imaging (MRI) findings alleged to be specific for vertebral fractures caused by malignant lesions. Using such findings for differential diagnosis is often difficult, especially during the early phase of the fracture. With the relative inaccuracy of any single imaging finding, a validated scoring system based on a combination of imaging findings might lead to enhanced diagnostic accuracy. The purpose of this study was to establish a diagnostic scoring system for discriminating osteoporotic vertebral fractures from those caused by malignant tumors on the basis of MRI and computed tomography (CT) findings. METHODS: Ten MRI and CT scan findings of 57 osteoporotic vertebral fractures and 43 neoplastic fractures were retrospectively evaluated for their ability to discriminate between malignant and benign vertebral fractures. RESULTS: The following four MRI and two CT findings were selected as the basis for the scoring system: pedicle or other posterior element involvement; extension into the paravertebral region; preservation of normal bone marrow signal; a continuous black line representing the posterior vertebral body margin on T2-weighted MRI images; osteolytic destruction; and distinct fracture lines on CT. CONCLUSION: By combining the findings common to MRI and CT scans of vertebral fractures, a simple scoring system was devised. This scoring system was found to enhance the accuracy of imaging diagnosis of fractures caused by benign or malignant spinal lesions.

Surgical treatment with instrumentation for severely destructive spondyloarthropathy of cervical spine.

Nine patients with severely destructive spondyloarthropathy and marked neurologic deficits associated with dialysis-related amyloidosis underwent posterior decompression and fusion by means of instrumentation at our institute. All patients showed segmental kyphosis, six patients vertebral ankylosis, and eight patients spondylolisthesis. Spondylolisthesis at two levels was noted in three patients. Of the 11 levels of spondylolisthesis in all, 9 were proximally adjacent and 2 were distally adjacent to vertebral ankylosis. All patients underwent posterior decompression and multisegment fusion with autogenous iliac bone. From three to five spinal segments were fixed. Seven patients underwent posterior fusion by means of a pedicle or lateral mass screw between levels C3 and C7, one patient between C3 and C6, and one between C3 and T1. The clinical rate of improvement at the final follow-up was 74.3%. Though complete stability could not be achieved in three patients, the results were rated as good. No postoperative neurologic deterioration has been observed in this series, nor did any patients die immediately after surgery or during the postoperative follow-up period. As anterior long-span surgery might be too invasive for hemodialysis patients, we think that posterior decompression and fusion may well be a reasonable and effective strategy for severe hemodialysis-associated cervical spondyloarthropathy with neurologic deficits. To achieve complete stability, 360 degrees fusion with both anterior and posterior fixation with instrumentation may be required for these patients.

[Vertebroplasty].

Vertebroplasty for pseudoartrosis of vertebral fracture using PMMA (polymethylmetacrylate) or CPC (calcium phosphate cement) is a new less invasive surgical method providing sufficient pain relief and correction of kyphosis.

Electrochemotherapy for digital chondrosarcoma.

Electrochemotherapy (ECT) delivers nonpermeable anticancer drugs to cell interiors by temporally increasing the permeability of the cytoplasmic membrane under locally applied pulsating electrical stimuli. This treatment results in consistent and enhanced pharmacological effects of drugs on the targeted tissue. ECT has been used for surface skin cancer but never for musculoskeletal tumors. This report describes a clinical trial of ECT for digital chondrosarcoma. A 74-year-old woman with a digital chondrosarcoma was administered electric stimulation with two surface electrodes 10 min after intratumoral multiple injection of bleomycin sulfate and 15 s after intraarterial perfusion of bleomycin sulfate. Biopsy performed after ECT showed 90% tumor necrosis. Marginal resection of the tumor was followed by autologous bone grafting to fill the bone defect. Although the follow-up period was short (3 years), the patient remained disease-free after ECT and was satisfied that amputation of the affected finger could be avoided. This preliminary result suggests that ECT is a viable modality for limb-preserving treatment of patients with sarcoma of the extremities.

Anterior thoracic spinal fusion in dogs by injection of recombinant human bone morphogenetic protein-2 and a synthetic polymer.

The purpose of this study was to achieve spinal fusion in the absence of bone graft material using a new, injectable, and semi-liquid synthetic polymer (polylactic acid polyethylene glycol [PLA-PEG] block copolymer) containing recombinant human bone morphogenetic protein-2 (rhBMP-2). Twenty-seven skeletally mature beagles underwent anterior thoracic spinal fusion at T9-T10. Group I (n = 9) was injected with 1 mL of PLA-PEG block copolymer carrier alone into space under the vertebral pleura and the anterior longitudinal ligament. Group II (n = 9) was injected with 1 mL of PLA-PEG carrier containing 500 microgram of rhBMP-2. Group III (n = 9) was injected with 1 mL of PLA-PEG carrier containing 1000 microgram of rhBMP-2. In the Group I animals, no evidence of new bone formation was noted at the implanted sites both radiographically and histologically. In contrast, all of the nine animals in Group III showed new bone formation in 12 weeks, and four of the nine animals in Group II showed bony mass at the injected sites. However, vertebral bony fusion was incomplete despite the significant amount of new bone formation in both groups that showed new bone formation. In addition to resulting in improvements in the surgical procedure, injection of rhBMP-2 and a synthetic polymer is useful for bone formation for spinal fusion.

Clinical outcome and survival after palliative surgery for spinal metastases: palliative surgery in spinal metastases.

BACKGROUND: The authors sought to identify treatment-related factors that influenced survival after surgical treatment for metastatic spinal tumors and to evaluate the relationship between survival and postoperative ambulation time as a factor related to quality of life. METHODS: The medical records of 81 patients with metastatic spinal tumors who underwent palliative surgery at the study institution were assessed. Univariate analysis for factors influencing survival used the Kaplan-Meier log rank statistic and multivariate analysis used the Cox proportional hazards model. The Spearman correlation test was used to analyze the relationship between postoperative ambulation and survival time. RESULTS: The patients had a median age of 59.9 years and a median survival of 10.6 months after surgery. For patients, postoperative ambulatory median survival was 16.5 months and median ambulation time was 13.8 months. By univariate analysis, anatomic site of the primary tumor, postoperative ambulation, and combined adjuvant therapy (chemotherapy plus radiotherapy) were associated with prolonged survival (P < 0.05). Multivariate analysis identified primary site and postoperative ambulatory function as independent predictors of prolonged survival (P < 0.0001). Significant correlations were found between ambulation time and survival time of patients who were able to walk after surgery (P < 0.0001), even in patients with liver (P < 0.05) or lung carcinoma (P < 0.05). CONCLUSIONS: The anatomic site of primary carcinoma and postoperative ambulation were associated with longer survival after palliative surgery for metastatic spinal tumor. When ambulation is attained after surgery, it can be preserved until late in remaining life even when the primary tumor is unfavorable. Palliative surgery for spinal metastasis can improve the quality and quantity of life.

Mechanism for the action of bone morphogenetic proteins and regulation of their activity.

Although the bone morphogenetic proteins (BMPs) are multifunctional proteins, implantation of osteogenic BMPs such as BMP-2 and BMP-7 at an osseous or extraosseous site results in bone and cartilage formation. These molecules are soluble, local-acting signaling proteins, which bind to specific receptors on the surface of the cell. The receptors then transduce the signal via a group of proteins called Smads, which in turn activate particular genes. In vivo, these BMPs act primarily as differentiation factors, turning responsive mesenchymal cells into cartilage- and bone-forming cells. A summary of the in vitro and in vivo studies suggests that implantation of these BMPs stimulates cells from the soft and hard tissues (e.g., muscle, bone marrow, periosteum) to become bone, and in some cases, cartilage forming cells. The activity of BMPs is tightly controlled at many levels. The tissue-specific transcription factor (basic helix-loop-helix factor) and its binding sequence (E-box) together play a critical role in deciding the expression of BMPs. Outside the cell, soluble inhibitory proteins such as noggin, chordin, and follistatin can bind certain of the BMPs and inhibit their binding to cell surface receptors. Inside the cell, the activity of BMPs is controlled through the combination of signal-transducing and inhibitory Smad proteins. Bone morphogenetic proteins can upregulate expression of the inhibitory Smad proteins. These Smads are phosphorylated and translocate into the nucleus, where they regulate the transcription of target genes together with other transcription factors including PEBP2alphaA/Cbfa1. Cooperation between PEBP2alphaA/Cbfa1 and BMP-activated Smad (Smad1/5) in the nucleus induces the expression of the genes related to the osteoblast phenotype. In addition, a number of negative regulators of BMP action exist within the nucleus. All of these regulatory mechanisms together cause the bone-induction process to be controlled tightly and self-limiting. Thus, bone induction is observed only locally at the site of BMP and matrix implantation, as defined by the volume of matrix, and it is limited temporally only to the time when the BMP is present.

Pro-inflammatory and anti-inflammatory cytokine increases after spinal instrumentation surgery.

We investigated the effects of instrumentation on postoperative inflammatory reaction and identified standard changes in serum cytokine concentrations after spinal surgery. Pro-inflammatory cytokines [interleukin (IL)-6 and IL-8] and anti-inflammatory cytokines [IL-10, IL-1 receptor antagonist (ra), and soluble tumor necrosis factor receptors (sTNF-R) I and II] were assayed in serum from seven patients with lumbar spinal posterior decompression, six with spinal decompression and posterolateral fusion without instrumentation and seven with spinal decompression and posterolateral fusion with instrumentation. All cytokines after spinal instrumentation increased significantly more than in other groups on postoperative days 0 and 1. Seven days after SI, IL-6, -8, and -10 had normalized, but IL-1ra and sTNF-RI and sTNF-RII remained elevated. Both pro-inflammatory and anti-inflammatory cytokines were enhanced by implants in the acute phase, whereas only anti-inflammatory cytokines were enhanced by instruments in the subacute phase.

FK506 enhanced osteoblastic differentiation in mesenchymal cells.

Bone morphogenetic protein (BMP) is a bone-derived growth factor capable of promoting the differentiation of mesenchymal cells into osteogenic lineage pathways. Recently, immunosuppressants were reported to cause a moderate increase in osteoblastic differentiation in a rat osteoblast-like osteosarcoma cell line. If immunosuppressants can induce osteoblastic differentiation, it will be useful for bone tissue transplantation. We assessed the effect of immunosuppressants with or without BMP-4 on inducing osteoblastic differentiation in osteoblast-like and other mesenchymal cells. FK506, an immunosuppressant often used clinically, induced a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, one of the markers of osteoblast differentiation, in cells derived from mesenchyma. In the presence of BMP-4, ALP activity, mRNA levels of ALP and osteocalcin increased. FK506 was found to not only stimulate osteoblastic differentiation, but also to enhance BMP-4 induced osteoblastic differentiation. These results suggest that FK506 promotes differentiation of osteoblastic cells.