Diagnostic value of MRI in coexistence of schwannoma and meningioma mimicking a single dumbbell-shaped tumor in high cervical level. Case series and literature review.

CONTEXT: Concurrent schwannoma and meningioma arising in the high cervical level mimicking a single dumbbell-shaped tumor is significantly rare, most of them were found during the surgeries or postoperative histological findings unexpectedly. The specific feature of schwannoma and meningioma coexistence in high cervical level on MR images has not been clearly described yet. FINDINGS: We presented four cases of concurrent extradural schwannoma and intradural meningioma mimicking a single dumbbell-shaped tumor arising in the high cervical level. There was no interconnection between intradural and extradural masses in any case. In MRI reviews, the signal intensity between intradural lesions and spinal cord was similar on T2 weighted MR images. However, on contrast-enhanced MR images, the intradural lesions were more enhanced than spinal cord and presented as crescent-shaped intradural minor lesions adjacent to the more significantly enhanced extradural major tumor. These MRI findings could not be easily identified without meticulous observation preoperatively. Postoperative pathological findings confirmed the discrete tumors arising in the same cervical level. CONCLUSION: The comparison of signal intensity changes among the spinal cord, intradural tumor and extradural tumor between T2 weighted and contrast-enhanced MR images may be helpful to predict coexistent schwannoma and meningioma in the high cervical level preoperatively. Intradural exploration is highly recommended when less enhanced crescent-shaped intradural minor lesion was observed adjacent to the significantly enhanced dumbbell-shaped major tumor in preoperative MRI findings.

A novel technique of transpedicular opening-wedge osteotomy for treatment of rigid kyphosis in patients with ankylosing spondylitis.

BACKGROUND: To investigate the effectiveness and feasibility of a novel vertebral osteotomy technique, transpedicular opening-wedge osteotomy (TOWO) was used to correct rigid thoracolumbar kyphotic deformities in patients with ankylosing spondylitis (AS). METHODS: Eighteen AS patients underwent TOWO to correct rigid thoracolumbar kyphosis. Radiographic parameters were compared before surgery, 1 week after surgery and at the last follow-up. The SRS-22 questionnaire was given before surgery and at the last follow-up to evaluate clinical improvement. The operating time, estimated blood loss and complications were analyzed. RESULTS: The mean operating time and estimated blood loss were 236 min and 595 ml, respectively. The mean preoperative sagittal vertical axis (SVA), thoracic kyphosis (TK), pelvic tilt (PT) and thoracolumbar kyphosis (TLK) were 158.97 mm, 51.24 mm, 43.63 mm and 41.74 mm, respectively, and decreased to 66.72 mm, 35.96 mm, 27.21 mm and 8.67 mm at the last follow-up. The mean preoperative lumbar lordosis (LL) and sacral slope (SS) were 8.30 ± 24.43 mm and 19.67 ± 9.40 mm, respectively, which increased to 38.23 mm and 28.13 mm at the last follow-up. The mean height of the anterior column of osteotomized vertebrae increased significantly from 25.17 mm preoperatively to 37.59 mm at the last follow, but the height of the middle column did not change significantly. SRS-22 scores were improved significantly at the last follow-up compared with preoperatively. Solid bone union was achieved in all patients after 12 months of follow-up, and no screw loosening, screw removal or rod breakage was noticed at the last follow-up. CONCLUSIONS: TOWO could achieve satisfactory kyphosis correction by opening the anterior column instead of vertebral body decancellation and posterior column closing, thus simplifying the osteotomy procedure and improving surgical efficacy.

Effect of Whitlockite as a new bone substitute for bone formation in spinal fusion and ectopic ossification animal model.

BACKGROUND: Bone substrates like hydroxyapatite and tricalcium phosphate have been widely used for promoting spinal fusion and reducing the complications caused by autograft. Whitlockite has been reported to promote better bone formation in rat calvaria models compare with them, but no study investigated its effect on spinal fusion yet. Also, the higher osteoinductivity of whitlockite raised concern of ectopic ossification, which was a complication of spinal fusion surgery that should be avoided. METHODS: In this study, we compared the osteoinductivity of whitlockite, hydroxyapatite, and tricalcium phosphate porous particles with SD rat spine posterolateral fusion model and investigated whether whitlockite could induce ectopic ossification with SD rat abdominal pouch model. RESULTS: The micro-CT result from the posterolateral fusion model showed whitlockite had slightly but significantly higher percent bone volume than tricalcium phosphate, though none of the materials formed successful fusion with surrounding bone tissue. The histology results showed the bone formed on the cortical surface of the transverse process but did not form a bridge between the processes. The result from the abdominal pouch model showed whitlockite did not induce ectopic bone formation. CONCLUSION: Whitlockite had a potential of being a better bone substrate hydroxyapatite and tricalcium phosphate in spinal fusion with low risk of inducing ectopic ossification.

Comparison of demineralized bone matrix and hydroxyapatite as carriers of Escherichia coli recombinant human BMP-2.

BACKGROUND: Autograft has been widely used in various orthopedic and dental surgery for its superior osteogenicity, osteoinductivity and osteoconductivity. But the available volume of the autograft is limited and the efficacy of it is highly affected by the condition of the patients. Therefore, growth factors such as Escherichia coli bone morphogenetic protein-2 (ErhBMP-2) has been widely used in some countries and regions with various carriers that could affect the effects of the growth factors. Demineralized bone matrix (DBM) has been widely used as a bone graft substitute and growth factor carrier, but its effect as a carrier of ErhBMP-2 was less investigated. MATERIALS AND METHODS: Rat calvaria defect model was used in this study. We implanted ErhBMP-2 with DBM or hydroxyapatite (HA) as a carrier in 8 mm calvaria defect and compared their bone regeneration effect in 4th week and 8th week after implantation with micro-CT and histology. The data was analyzed with one-way ANOVA method with Bonferroni post-hoc analysis. RESULT: The group with DBM as the carrier showed significantly higher bone volume and bone thickness than the groups with HA as the carrier in both weeks. And the histology sections showed less adipose tissue formed in the groups with DBM as the carrier. CONCLUSION: DBM could be a better carrier for ErhBMP-2 than HA.

Clinical outcomes of selective fusion for the thoracolumbar-lumbar curve in patients with Lenke type 6C adolescent idiopathic scoliosis: a preliminary study.

Limited evidence is available in the literature regarding the fate of the unfused structural thoracic curve following selective thoracolumbar-lumbar curve fusion (SLF) in Lenke 6C adolescent idiopathic scoliosis (AIS) patients. Therefore, we compared the outcomes of SLF between Lenke 6C and 5C AIS patients. We retrospectively reviewed 31 patients Lenke 5C (n = 18) and Lenke 6C (n = 13) AIS patients who underwent SLF at a single institution. Multiple radiological parameters were measured using whole-spine radiographs taken before and after surgery and at the last follow-up visit. SRS-22 at the final follow-up was obtained for clinical assessment. A total of 31 patients with a mean age of 14.6 years at operation who were followed for a mean of 6.4 years were included in this study. The Cobb angle of the unfused thoracic curve was spontaneously corrected immediately following SLF and increased slightly but not significantly at the final follow-up in both groups (Lenke 5C: pre 33.0°, post 14.4°, final 19.4°, Lenke 6C: pre 46.1°, post 31.7°, final 34.2°). At every time point, the thoracic Cobb angle was significantly larger in the Lenke 6C. SRS-22 score at the final follow-up, including the self-image domain, did not differ between the two groups. In this study, SLF for Lenke 6C AIS achieved a significant spontaneous correction of the unfused thoracic curve and yielded a comparable SRS-22 result at the final follow-up to that of Lenke 5C. Our findings suggest that SLF is a viable treatment option for Lenke 6C AIS.

The toxicological effect of 4-week repeated intravenous injection of activin a/BMP-2 chimera and 2-week recovery study in Beagle dog.

The purposes of this study was to determine the toxicological effect of repeated intravenous administration of Activin A/BMP-2 chimera (AB204) in beagle dogs for a long period of four weeks and evaluate two-week recovery. AB204 was administered at doses of 0.08, 0.16, or 0.32 mg/kg/day to three male and three female beagle dogs for 4 weeks as the experimental group. For the control group, sterile saline was administered to three male and three female beagle dogs. For the two-week recovery test, two male and two female beagle dogs were randomly selected from the control group and the 0.32 mg/kg/day administered experimental group. General symptoms, body weight, food consumption, ophthalmological examination, electrocardiogram, urinalysis, hematology and blood biochemistry, organ weights, autopsy, and histopathological examination were observed or conducted. No animals died. There was no significant difference in any parameter evaluated between the experimental group and the control group. Histopathological examination revealed compound inflammation at the administration site in both the experimental group and the control group. The inflammation disappeared during the two-week recovery. These results indicated that repetitive intravenous injection of AB204 in beagle dog for a long period of four weeks did not show any toxicity. Therefore, no observed adverse effects level (NOAEL) of AB204 was 0.32 mg/kg/day in big animal model.

Removal of the Deeply Located Intradiskal Broken Knife Blade with Arthroscopic Assistance: Case Report and Literature Review.

BACKGROUND: Surgical scalpel broken is rarely reported in posterior lumbar discectomy or fusion surgeries, but when it happens and even the broken part is deeply located in the disk space, there is no guideline to remove it during the initial surgery. CASE DESCRIPTION: A 56-year-old female with L3-L4 and L4-L5 disk herniation and stenosis underwent 2-level transforaminal lumbar diskectomy and fusion. The knife blade was broken in the L4-L5 disk space during the annulus resection. Despite a 1.5-hour trial for removal with fluoroscopy, the broken part gradually migrated to the anterior border of the disk space. Eventually, arthroscopy was used for retrieval, the blade tip was clearly recognized in the arthroscopic view, which improved the accuracy of the subsequent operation. The blade fragment was removed successfully within 30 minutes. CONCLUSIONS: Arthroscopic retrieval of a broken scalpel deeply located in the intradiskal space is recommended as an alternative method when conventional effort is unable to remove it, especially when the broken blade migrates anteriorly, which may provoke catastrophic consequences.

Escherichia coli BMP-2 showed comparable osteoinductivity with Chinese hamster ovary derived BMP-2 with demineralized bone matrix as carrier.

Escherichia coli bone morphogenetic protein-2 (ErhBMP-2) had a larger yield but less osteoinductivity than Chinese hamster ovary cell bone morphogenetic protein-2 (CrhBMP-2). Since the release profile of rhBMP-2 affects its osteoinductivity, an appropriate carrier could improve the effect of ErhBMP-2. Demineralized bone matrix (DBM) was one of the most widely used bone substitutes, but few studies evaluated the osteoinductivity of ErhBMP-2 while it was carried by DBM. Therefore, we compared the osteoinductivity of ErhBMP-2 with CrhBMP-2 with DBM as the carrier of each. In vitro results showed ErhBMP-2 had slightly less osteoinductivity than CrhBMP-2. However, with DBM as the carrier, ErhBMP-2 induced significantly more bone regeneration in rat calvaria defects. Therefore, ErhBMP-2 might have comparable osteoinductivity with CrhBMP-2 while carried by DBM.

Comparison of the osteogenesis and fusion rates between activin A/BMP-2 chimera (AB204) and rhBMP-2 in a beagle's posterolateral lumbar spine model.

BACKGROUND CONTEXT: Activin A/BMP-2 chimera (AB204) could promote bone healing more effectively than recombinant bone morphogenetic protein 2 (rhBMP-2) with much lower dose in a rodent model, but there is no report about the effectiveness of AB204 in a large animal model. PURPOSE: The purpose of this study was to compare the osteogenesis and fusion rate between AB204 and rhBMP-2 using biphasic calcium phosphate (BCP) as a carrier in a beagle's posterolateral lumbar fusion model. STUDY DESIGN: This is a randomized control animal study. METHODS: Seventeen male beagle dogs were included. Bilateral posterolateral fusion was performed at the L1-L2 and L4-L5 levels. Biphasic calcium phosphate (2 cc), rhBMP-2 (50 µg)+BCP (2 cc), or AB204 (50 µg)+BCP (2 cc) were implanted into the intertransverse space randomly. X-ray was performed at 4 and 8 weeks. After 8 weeks, the animals were sacrificed, and new bone formation and fusion rate were evaluated by manual palpation, computed tomography (CT), and undecalcified histology. RESULTS: The AB204 group showed significantly higher fusion rate (90%) than the rhBMP-2 group (15%) or the Osteon group (6.3%) by manual palpation. On x-ray and CT assessment, fusion rate and the volume of newly formed bone were also significantly higher in AB204 group than other groups. In contrast, more osteolysis was found in rhBMP-2 group (40%) than in AB204 group (10%) on CT study. In histologic results, new bone formation was sufficient between transverse processes in AB204 group, and obvious trabeculation and bone remodeling were observed. But in rhBMP-2 group, new bone formation was less than AB204 group and osteolysis was observed between the intertransverse spaces. CONCLUSIONS: A low dose of AB204 with BCP as a carrier significantly promotes the fusion rate in a large animal model when compared with the rhBMP-2. These findings demonstrate that AB204 could be an alternative to rhBMP-2 to improve fusion rate.

In vitro and in vivo evaluation of osteoinductivity and bone fusion ability of an activin a/BMP2 chimera (AB204): a comparison study between AB204 and rhBMP-2.

This study compared osteoinductivity and osteogenic capacity between AB204 and rhBMP-2 using hMSCs in vitro and a beagle's posterolateral spinal fusion model. Cultured hMSCs were treated with AB204 or rhBMP-2 with low to high doses. Three male beagles were performed posterolateral spinal fusion with biphasic calcium phosphate (2 ml) + AB204 or rhBMP-2 (20, 50 or 200 µg). They were euthanized after 8 weeks. The fusion rate and bone formation of spine samples were examined. AB204 had higher alkaline phosphatase activity, mineralization and osteogenic-related gene expression than rhBMP-2. Fusion rates in all rhBMP-2 groups were 0. They were 100% for 50 µg and 200 µg AB204 groups. Therefore, AB204 showed higher osteogenicity than rhBMP-2. It could be a better bone graft substitute.

In Vitro and In Vivo Evaluation of Whitlockite Biocompatibility: Comparative Study with Hydroxyapatite and ß-Tricalcium Phosphate.

Biomimicking ceramics have been developed to induce efficient recovery of damaged hard tissues. Among them, calcium phosphate-based bioceramics have been the most widely used because of their similar composition with human hard tissue and excellent biocompatibilities. However, the incomplete understanding of entire inorganic phases in natural bone has limited the recreation of complete bone compositions. In this work, broad biomedical evaluation of whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12), which is the secondary inorganic phase in bone, is conducted to better understand human hard tissue and to seek potential application as a biomaterial. Based on the recently developed gram-scale method for synthesizing WH nanoparticles, the properties of WH as a material for cellular scaffolding and bone implants are assessed and compared to those of hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and ß-tricalcium phosphate (ß-TCP: ß-Ca3(PO4)2). WH-reinforced composite scaffolds facilitate bone-specific differentiation compared to HAP-reinforced composite scaffolds. Additionally, WH implants induce similar or better bone regeneration in calvarial defects in a rat model compared to HAP and ß-TCP implants, with intermediate resorbability. New findings of the properties of WH that distinguish it from HAP and ß-TCP are significant in understanding human hard tissue, mimicking bone tissue at the nanoscale and designing functional bioceramics.

The inhibitory effect of zoledronate on early-stage osteoinduction by recombinant human bone morphogenetic protein 2 in an osteoporosis model.

This study evaluated the effect of the combined treatment of intravenous zoledronic acid (ZA, 0.08 mg/kg) and rhBMP-2 (5 µg) on osteogenesis in a calvarial defect model of ovariectomized SD rats. New bone formation was evaluated 4 or 8 weeks after calvarial defect implantation using micro-CT and histology. Micro-CT results revealed that the rhBMP-2 group showed significantly higher calvarial defect coverage ratio compared with the ZA + rhBMP-2 group at 4 weeks. In addition, bone formation indices were significantly lower in ZA + rhBMP-2 group when compared with the rhBMP-2 group after 4 weeks, which indicates a negative effect of ZA on the initial bone formation and the bone quality. At 8 weeks, the negative effect induced by ZA treatment was alleviated as time passed. Histological examination showed similar results to the micro-CT measurements. In conclusion, although ZA treatment lowered the new bone formation induced by rhBMP-2 initially, as time passed, the negative effect was decreased.

Effects of Ovariectomy and Corticosteroid-Induced Osteoporosis on the Osteoinductivity of rhBMP-2 in a Segmental Long-Bone Defect Model.

This study used the segmental long-bone defect model to assess the effects of osteoporosis on the formation of new bones and the osteoinductivity of recombinant human bone morphogenetic protein-2 (rhBMP-2). Seventy-two female Sprague-Dawley rats were divided into two groups: an osteoporosis group with ovariectomies and dexamathasone intramuscular injections and a sham group. When they reached 22 weeks in age, each group was further divided into two groups and a 5-mm defect was made in both fibular mid-shafts of each rat. One fibula in each rat was picked randomly and was injected with 0.05 mL of hydrogel carrier; the opposite fibula was injected with the same carrier mixed with rhBMP-2 (10 µg). After rearing for a further 5 and 9 weeks, the ratios of the lengths of the newly formed bones in the fibular defects were determined using micro-CT and undecalcified histology. The sham rhBMP-2-injected group-in all of the 5- and 9-week-kept groups-showed a significantly higher bridging bone formation ratio than the other three groups. The osteoporosis rhBMP-2-injected group showed a significantly higher ratio than both the non-rhBMP-2-injected sham hydrogel and the osteoporosis hydrogel groups. The comparison of the micro-CT parameters of the newly formed bones showed that the sham rhBMP-2 group at both 5 and 9 weeks compared with the osteoporosis rhBMP-2 group had significantly higher percentage bone volumes, trabecular thicknesses, and trabecular numbers, in addition to significantly lower specific surfaces, trabecular pattern factors, and structural model indices. The histology results showed that the sham-rhBMP-2 group began forming bridging bones in the defect areas at 5 weeks, and at 9 weeks, trabeculae and marrow spaces were observed. However, the osteoporosis rhBMP-2 group exhibited a relatively minor level of new bone and trabecula formation. Consequently, the rhBMP-2 group showed significantly increased bone formation in the osteoporosis rat fibular defect model compared with the hydrogel group, whereas the new bone quantities, qualities, and remodeling in the osteoporosis rhBMP-2 group were less effective than those in the sham-rhBMP-2 group, signaling that ovariectomy and corticosteroid-induced osteoporosis significantly undermines rhBMP-2 osteoinductivity.

Fabrication of an rhBMP-2 loaded porous ß-TCP microsphere-hyaluronic acid-based powder gel composite and evaluation of implant osseointegration.

Methods to improve osseointegration that include implantation of rhBMP-2 with various kinds of carriers are currently of considerable interest. The present study was conducted to evaluate if the rhBMP-2 loaded ß-TCP microsphere-hyaluronic acid-based powder-like hydrogel composite (powder gel) can act as an effective rhBMP-2 carrier for implantation in host bone with a bone defect or poor bone quality. The release pattern for rhBMP-2 was then evaluated against an rhBMP-2-loaded collagen sponge as a control group. Dental implants were also inserted into the tibias of three groups of rabbits: an rhBMP-2 (200 µg) loaded powder gel composite implanted group, an implant only group, and a powder gel implanted group. Micro-CT and histology of the implanted areas were carried out four weeks later. The rhBMP-2 powder gel released less rhBMP-2 than the collagen sponge, but it continued a slow release for more than 7 days. The rhBMP-2 powder gel composite improved osseointegration of the dental implant by increasing the amount of new bone formation in the implant pitch and it improved the bone quality and bone quantity of new bone. The histology results indicated that the rhBMP-2 powder gel composite improved the osseointegration in the cortical bone as well as the marrow space along the fixture. The bone-to-implant contact ratio of the rhBMP-2 (200 µg) loaded powder gel composite implanted group was significantly higher than those of the implant only group and the powder gel implanted group. The powder gel appeared to be a good carrier and could release rhBMP-2 slowly to promote the formation of new bone following implantation in a bone defect, thereby improving implant osseointegration.

The effects of recombinant human bone morphogenetic protein-2-loaded tricalcium phosphate microsphere-hydrogel composite on the osseointegration of dental implants in minipigs.

Bone formation in tooth defect areas and the osseointegration of dental implants are very important for successful dental implant surgery. The aim of the present study was to assess the strengthening effect of a ß-TCP microsphere-hydrogel composite containing recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone healing and implant osseointegration. The molars and premolars on the left and right sides of the maxilla were extracted from six male minipigs, and dental implants were placed using either the ß-TCP microsphere-hydrogel carrier alone or the carrier loaded with rhBMP-2 (500 µg). The animals were kept alive for a further 8 weeks. The molars and premolars from the left and the right sides of the mandibles of another six minipigs were extracted, and the animals were kept alive for 4 weeks. Two 5-mm-diameter bone defects were then made on both sides of the mandible. The defects were filled with saline, ß-TCP microsphere-hydrogel carrier, or the carrier loaded with rhBMP-2 (300 µg), and dental implant fixtures were inserted. The animals were kept alive for a further 4 weeks. Bone formation was examined using plane radiographs, micro-CT, and the histology of undecalcified specimens. The group treated with the rhBMP-2-loaded carrier composite showed a significantly higher percentage bone volume and a greater trabecular thickness for the newly formed bone in the tooth defect areas when compared to the group treated with the carrier alone. The rhBMP-2 group had a significantly higher osseointegration, a larger percentage bone volume, greater trabecular thickness in the newly formed bone in tooth defect areas, a larger newly formed bone fraction in the fixture pitch, and a greater number of newly formed trabecular bones when compared to the other groups. We confirmed that the rhBMP-2-loaded carrier composite promotes new bone formation after tooth extraction and strengthens osseointegration of dental fixtures by improving the degree of osseointegration around the dental implant fixture.