Effect of human amniotic fluid on bone healing

BACKGROUND: Bone healing continues to pose challenges for researchers and clinicians working in the field of plastic surgery. Complete bone regeneration cannot be obtained in critical size osseous defects without the application of osteogenic or osteoinductive bone material. In this study, we hypothesized that because extracellular matrix components are known to play a major role in the first steps of healing during bone or injury healing and because hyaluronic acid as chondroitin sulfate is recognized as an osteogenic compound without osteoinductive activity, human amniotic fluid, which contains high concentrations of hyaluronic acid, gyaluronic acid -stimulating activator, and other factors, might accelerate bone healing when applied subperiosteally to rabbit calvarial defects. MATERIALS AND METHODS: We created 20 calvarial defects in 10 12-week-old New Zealand white rabbits who were divided into 2 groups. Group 1 defects were instilled with human amniotic fluid, whereas the group with contralateral defects, i.e., group 2, were given with same amount of normal saline solution. We then measured the density of the bone that formed over the defects using computed tomography at the third, fourth, fifth, and sixth weeks postoperatively. After this period, the defects were harvested for histopathologic evaluation. RESULTS: The defects from group 1, which were treated with human amniotic fluid, showed significantly higher ossification than the group 2 defects, which were instilled with saline solution. Histological examination at 6 weeks postoperatively revealed that the defects treated with human amniotic fluid (group 1) had superior ossification compared with the control group defects (group 2). CONCLUSION: Because of its positive effects on bone healing and also because of its ability to be stored in deep freeze if made cell-free, human amniotic fluid would appear to be a useful adjunct in the treatment of bone healing.     

Oxysterols enhance osteoblast differentiation in vitro and bone healing in vivo.

Oxysterols, naturally occurring cholesterol oxidation products, can induce osteoblast differentiation. Here, we investigated short-term 22(S)-hydroxycholesterol + 20(S)-hydroxycholesterol (SS) exposure on osteoblastic differentiation of marrow stromal cells. We further explored oxysterol ability to promote bone healing in vivo. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, osteocalcin (OCN) mRNA expression, mineralization, and Runx2 DNA binding activity. To explore the effects of osteogenic oxysterols in vivo, we utilized the critical-sized rat calvarial defect model. Poly(lactic-co-glycolic acid) (PLGA) scaffolds alone or coated with 140 ng (low dose) or 1400 ng (high dose) oxysterol cocktail were implanted into the defects. Rats were sacrificed at 6 weeks and examined by three-dimensional (3D) microcomputed tomography (microCT). Bone volume (BV), total volume (TV), and BV/TV ratio were measured. Culture exposure to SS for 10 min significantly increased ALP activity after 4 days, while 2 h exposure significantly increased mineralization after 14 days. Four-hour SS treatment increased OCN mRNA measured after 8 days and nuclear protein binding to an OSE2 site measured after 4 days. The calvarial defects showed slight bone healing in the control group. However, scaffolds adsorbed with low or high-dose oxysterol cocktail significantly enhanced bone formation. Histologic examination confirmed bone formation in the defect sites grafted with oxysterol-adsorbed scaffolds, compared to mostly fibrous tissue in control sites. Our results suggest that brief exposure to osteogenic oxysterols triggered events leading to osteoblastic cell differentiation and function in vitro and bone formation in vivo. These results identify oxysterols as potential agents in local and systemic enhancement of bone formation.     

种植体联合骨组织工程技术修复犬下颌骨节段缺损的实验研究

目的 观察应用种植体联合骨组织工程技术,修复犬下颌骨节段缺损的效果。方法 体外扩增培养、成骨诱导犬BMSCs。将第2代细胞复合珊瑚后修复犬自体右侧下颌骨3 cm的节段缺损,术后32周植入种植体(实验组n=3);同时,以邻近正常骨植入种植体作为对照(n=3)。植入4周、12周、26周后,分别通过影像学、大体形态观察、组织学和生物力学等方法,检测骨缺损的修复效果。结果 植入后26周,X线片和CT均显示种植体与实验组及对照组骨质为良好骨性愈合,实验组种植体周围新生骨密度较高。Micro-CT显示,实验组骨密度和对照组间无显著性差别(P>0.05)。大体观察见种植体与组织工程骨和正常骨均形成紧密连接。组织学显示,实验组与对照组均有较多成熟骨结构。生物力学测试结果表明,实验组与正常下颌骨力学强度无显著性差异(P>0.05)。结论 自体成骨诱导BMSCs复合珊瑚形成的组织工程化骨,可较好地修复犬下颌骨节段缺损,植入种植体后可进一步促进骨成熟。     

Inhibition of bone healing by pamidronate in calvarial bony defects.

OBJECTIVE: Pamidronate has been studied as a therapeutic drug for various osteopenic diseases. However, avascular osteonecrosis in the jawbone has been recently reported in patients receiving pamidronate. The objective of this study was to examine the effect of pamidronate on bone regeneration in a controlled animal model. MATERIALS AND METHODS: To determine the effect of parmidronate on bone healing in a local bony defect area, a rabbit calvarial bony defect model was used and poly L-lactide-co-glycolide (PLGA) used as a drug carrier material. Four defect groups were made in each rabbit calvaria and the defects were treated as follows: untreated bony defect (group 1), PLGA only (group 2), 2 mg of pamidronate with PLGA (group 3), and 3 mg of pamidronate with PLGA (group 4). Bone healing was evaluated by radiography and histology at 1, 2, 4, 6, and 8 weeks after surgery. RESULTS: In radiographic analysis, radiopacity was lower in pamidronate groups than non-operated rabbit calvarial bone at all observation points (P < .05). In histological analysis, the initial bone formation at 1 week was not different among groups, but it was much lower in the pamidronate groups than in the control or PLGA group after 2 weeks. Newly formed bone at 1 week underwent avascular necrosis after 2 weeks in both pamidronate groups. Avascular necrosis was not observed until 8 weeks in both topically applied pamidronate groups. CONCLUSION: Collectively, pamidronate inhibits bone healing in rabbit calvarial bony defect and it may explain the avascular necrosis of the jaws in patients receiving pamidronate.     

Healing of an ulnar defect using a proprietary TCP bone graft substitute, JAX, in association with autologous osteogenic cells and growth factors

Currently, available synthetic bone substitutes have adequate osteoconductive properties but have little or no osteoinductivity. Recent research has focused on using osteogenic growth factors or cells to provide this. JAX is a beta tricalcium phosphate bone graft substitute that has a novel shape and interlocking design. This study investigated delivery methods and the use of autologous cell therapy to enhance healing of a bone defect using JAX as a scaffold. Bone marrow was harvested from 24 New Zealand White rabbits. The mononuclear cell fraction was isolated and culture expanded. Bilateral 1.5 cm defects in the ulna were filled with: Group 1: JAX alone, Group 2: JAX plus 1x10(7) autologous BMSCs injected at the time of surgery, Group 3: JAX plus 8x10(6) autologous BMSCs cultured on granules for 14 days prior to surgery, Group 4: JAX plus fresh bone marrow (BMA), Group 5: cortical autograft, Group 6: JAX plus 2.5 microg VEGF. Radiographs demonstrated that there was more new bone in the BMA and VEGF groups compared to JAX alone. Groups containing autologous BMSCs were only slightly better than JAX alone in the amount of bone in the defect but did improve bridging of the osteotomy. Histomorphometry identified a significant increase in bone volume in the BMA group compared to JAX alone. BMA and VEGF enhanced healing of bone defects whereas expanded BMSCs provided little advantage over scaffold alone. There was no difference between delivery methods of autologous BMSCs. These observations suggest that the provision of osteogenic cells alone is insufficient to enhance bone healing and that additional factors are required to initiate this process in vivo.     

The osteogenic potential of adipose-derived stem cells for the repair of rabbit calvarial defects

INTRODUCTION: Bone replacement is often necessary during reconstruction of craniofacial anomalies or trauma. Adipose-derived stem cells (ASCs) possess osteogenic potential and are a promising cell source for bone tissue engineering. The present study was designed to assess the osteogenic potential and utility of using ASCs to regenerate bone in a rabbit calvarial defect model. METHODS: Rabbit ASCs were seeded on gelatin foam (GF) scaffolds and induced in osteogenic medium containing bone morphogenetic protein (BMP)-2. Thirty-four 8-mm calvarial defects were randomly treated with autograft, no treatment, GF scaffold, GF + ASCs, or GF + osteoinduced ASCs. After 6 weeks, calvaria were harvested and underwent histologic and radiologic analyses to compare healing between the treatment groups. RESULTS: Defects treated with autograft underwent complete healing. Radiologically, there were no significant (P > 0.05) differences in healing among empty defects, and those treated with GF alone or GF plus osteoinduced ASCs. Osteoinduced ASCs exhibited significantly (P < 0.05) greater healing than noninduced ASCs. CONCLUSION: Preimplantation osteoinduction of ASCs enhances their osteogenic capacity. Lack of a significant osteogenic effect of ASCs on calvarial healing at 6 weeks may be secondary to use of noncritical-sized defects. Larger defects would likely demonstrate the osteogenic potential of ASCs more definitively.     

自体骨髓基质干细胞复合珊瑚修复犬下颌骨节段缺损的初步研究

目的应用自体骨髓基质干细胞(bonemarrowstromalcells,BMSCs)复合珊瑚构建组织工程化骨,修复犬下颌骨节段性缺损。方法体外扩增培养、成骨诱导犬BMSCs。将第二代细胞复合珊瑚后修复犬自体右侧3cm的下颌骨节段缺损(n=6);以单纯珊瑚植入缺损处为对照(n=6),术后12、32周分别通过影像学,大体形态观察,组织学和生物力学的方法检测骨缺损的修复效果。结果成骨诱导的BMSCs在珊瑚支架上生长良好。X线片显示12周时实验组骨痂较多,对照组材料明显吸收;32周时CT、X线片和大体观察显示术后实验组骨愈合良好,对照组为骨不连;骨密度检测示实验组显著高于对照组(P<0.05);组织学示实验组有较多成熟骨呈骨性愈合,对照组为纤维性愈合;生物力学测试实验组与正常下颌骨力学强度差异无统计学意义(P>0.05)。结论自体成骨诱导BMSCs复合珊瑚形成的组织工程化骨可修复犬下颌骨节段缺损。     

Accuracy of extraoral tuned aperture computed tomography (TACT) for proximal caries detection.

OBJECTIVES: The objectives of this study were to compare the difference in the accuracy of proximal caries detection by extraoral tuned aperture computed tomography (TACT), intraoral TACT, and film radiographs. STUDY DESIGN: Eighty proximal surfaces of 40 extracted human maxillary teeth were used. A digital sensor was the image receptor for TACT. Film radiographs were acquired using Insight film. Nine basis images were acquired to reconstruct TACT slices. Seven observers scored the presence or absence of proximal caries using the 3 imaging modalities. The true presence of caries and its depth were determined using the sectional images obtained by micro CT. Among the image modalities and observers, possible differences in the area under the receiver operating characteristic curve were assessed by analysis of variance (ANOVA). RESULTS: ANOVA indicated no statistically significant differences between observers (P = .845), modalities (P = .657), and observer-modality combinations (P = .593). CONCLUSION: Within the limited range of this study, extraoral TACT was not statistically different from intraoral TACT or film radiographs for proximal caries detection. This suggests that extraoral TACT may have some clinical utility for caries diagnosis and that further study may be warranted.     

Comparison of accuracy of three-dimensional spiral computed tomography, standard radiography, and direct measurements in evaluating facial fracture healing in a rat model

Complex maxillofacial fractures demand a detailed understanding of the three-dimensional (3D) pattern of injury. Evaluation of the outcome of the facial fracture repair additionally requires optimal demonstration of fracture gap, bony union, fibrous callus or incorporation of fracture ends, presence of incomplete fusion, or pseudoarthrosis. Although 3D computed tomography (CT) is reliably used for the diagnosis of complex facial fractures, its value in facial fracture healing is unknown. An experimental study was conducted to determine the accuracy of 3D spiral CT scans in evaluating facial fracture healing during the early and late postoperative periods. In 10 adult Wistar Albino rats, a standardized bone defect (3 mm) was created within the mid portion of each zygomatic arch (n = 20). At 10 and 20 weeks postfracture, gap distance displayed by 3D CT and plane radiography (posteroanterior) were measured. At 20 weeks postfracture, intraoperative measurement was also performed. A comparison between 3D CT, radiography, and intraoperative findings was performed. At 10 weeks postfracture, the fracture sites displayed larger bone defects in imaging with 3D CT than with plane radiography. The difference between groups was statistically significant (P < 0.05). The mean defect size imaged by 3D CT was 0.91 +/- 0.82 mm (standard deviation) and by plane radiography was 0.42 +/- 0.16 mm. At 20 weeks postfracture, the mean defect size imaged by 3D CT was 0.56 +/- 0.64 mm, and by plane radiography was 0.38 +/- 0.22 mm. The difference between groups was not statistically significant (P > 0.05). The defect size imaged by both plane radiography and 3D CT was significantly less than the measurement obtained from the intraoperative assessment (P < 0.05). It was concluded that 3D CT has limited benefit in the detection of newly formed bone at week 10 and in the detection of fibrous callus, which can eventually give rise to the bony tissue. Plane radiography is more valid during the early postoperative period (week 10), because it can detect the fibrous callus and newly formed bone more precisely. Gap distance between fracture ends could be determined by 3D CT accurately at week 20, although there was a tendency, which was not statistically significant, to overestimate the amount of bone defect measured by 3D CT when compared with that of plane radiography.     

Correlation of Computed Tomography with Histology in the Assessment of Periprosthetic Defect Healing

Computed tomography (CT) may more accurately assess the healing of grafted osteolytic lesions around acetabular components compared with plain radiographs, although clinical validation is lacking. To determine whether clinical or micro-CT imaging could assess accurately the grafted lesion compared with histology, we therefore quantified bone healing and ingrowth to determine an effective rhBMP-2 dose and ratio to allograft bone when grafted adjacent to a cementless porous-coated component. We grafted surgically created acetabular defects in canines (n = 20) before uncemented total hip arthroplasty. At 6 weeks, embedded acetabula were imaged and the CT slice images matched to histology section images. The percentage of bone in the defect and growth into the porous surface was assessed quantitatively. Low-dose rhBMP-2 with allograft (1:5 ratio) resulted in a higher percentage of defect healing (43.8%) than rhBMP-2 alone (29.2%) and a higher percentage of bone ingrowth (15.7%) than allograft bone alone (1.1%) as measured by histology. Micro-CT measurements were similar to histologic measurements of defect healing, whereas clinical CT overestimated periprosthetic bone by 38%. Neither clinical CT nor micro-CT techniques are adequate for assessing ingrowth or the bone-implant interface with metal artifacts.     

Treatment of nonunions and osseous defects with bone graft and calcium sulfate

The treatment of long bone nonunions and fractures with osseous defects is challenging. The results of 26 patients with either a persistent long bone nonunion or an osseous defect after an open fracture were reviewed. Each patient was treated with debridement of devitalized tissue, open reduction and internal fixation, and bone grafting using a mixture of autogenous iliac crest bone graft and medical grade calcium sulfate. The current study evaluated the union rate and associated complications for treatment of these injuries using this protocol. Each nonunion was confirmed intraoperatively, and healing was determined clinically by the patients' return to full activities without pain and radiographically by the presence of bridging trabeculae. Complications included persistent nonunion (four patients), wound drainage (five patients), wound drainage and cellulitis (one patient) and cellulitis alone (one patient). Using this treatment protocol, 22 patients (85%) achieved healing after one surgery and an additional two patients (92%) achieved healing after a second surgery. Medical grade calcium sulfate increases the volume of graft material, facilitates bone formation, and is safe in the treatment of nonunions and fractures with osseous defects.     

Implantation With New Three‐Dimensional Porous Titanium Web for Treatment of Parietal Bone Defect in Rabbit

Titanium net (meshes) with excellent mechanical properties can promote bone compatibility and has been used as a repairing material for bone defects in clinical settings. In the present study, using spiral computed tomography (CT) and histomorphlogical techniques, we investigated the effect of a novel kind of titanium web with a three‐dimensional (3D) porous structure on bone formation in rabbit skull (os parietal) defect. The images from the spiral CT scan demonstrate that the titanium web is completely fused with the surrounding bone tissue, even at the first month after implantation. The histomorphological findings show that different cells and tissues, including osseous tissue, connective tissue, and adipose cells, can easily grow into the 3D scaffold meshes of the titanium web, even in the center of the web and combine together as a whole body, suggesting that the titanium web possesses a very good biocompatibility, which is beneficial to the growth of bone tissue and promotes healing of the defected rabbit skull.     

丝素蛋白/羟基磷灰石组织工程化骨修复兔桡骨节段性骨缺损

目的 探讨丝素蛋白/羟基磷灰石(SF/HA)组织工程化骨的成骨作用,以期为临床治疗骨缺损提供新的人工骨材料.方法 将SF/HA与成骨诱导的兔骨髓基质干细胞(BMSCs)复合,构建组织工程化骨.取54只兔于左侧桡骨中上段制备15 mm节段性骨缺损.实验分3组(A、B组各24只,C组6只):A组:植入SF/HA组织工程化骨,B组:单纯植入SF/HA;C组:骨缺损区不植入任何材料.于术后4、8、12及16周摄X线片,并于16周行螺旋CT扫描重建,观察骨缺损修复及骨塑形情况,参照Lane-Sandhu X线评分标准对各组骨缺损的骨修复程度评分.骨痂标本行 HE染色组织学观察,按照Lane-Sandhu组织学评分法比较12周和16周时各组的骨修复情况. 结果 术后16周,X线片示A组髓腔通畅,新骨塑形好,骨皮质连续;B组缺损区有缩小,两断端不连接;C组缺损区无明显骨痂生长.16周时螺旋CT扫描重建显示:A组骨塑形明显,骨缺损完全修复;B组有部分皮质骨形成,缺损区不能完全修复;C组骨缺损基本无修复.每组术后4、8、12、16周不同时间点的放射学评分差异均有统计学意义(P＜0.05).术后12、16周时3组间Lane-Sandhu组织学评分差异均有统计学意义(P＜0.05). 结论 SF/HA组织工程化骨具有良好的节段性骨缺损修复能力,但SF/HA本身缺乏骨诱导作用,单独修复节段性骨缺损作用有限.     

The effects of multiple high-resolution peripheral quantitative computed tomography scans on bone healing in a rabbit radial bone defect model

The use of in vivo high-resolution computed tomography (CT) scanners provides the unique opportunity for evaluating temporal progression in healing of bone defects. However, these in vivo scanners impose ionizing radiation that could affect the healing and morphology of the bone. The primary objective of this study was to determine the effects of in vivo scanning at 2-week intervals on bone healing of a critical sized radial defect in rabbits and to investigate the effect of this radiation protocol on bone marrow cell viability using clinically applicable radiation doses. Thirty male rabbits were randomized into three groups: two groups received a 15 mm defect in the left radius that was filled with an autologous bone graft (DEF-CT and DEF-SHAM), and one group acted as an intact control (INT-CT). The duration of the study was 6 weeks. DEF-CT and INT-CT had high-resolution CT scans performed at 2-week intervals. The total cumulative radiation dose was 81.6 mGy per animal. DEF-SHAM received sham CT scans at the same time points. In group DEF-CT, the bone volume (BV) in the defect increased significantly over time (p ≤ 0.002, for all comparisons); the bone mineral density (BMD) in the defect decreased over time and was significantly lower at weeks 4 and 6 than at weeks 0 and 2 (p < 0.001, for all comparisons). In group INT-CT, BV and BMD did not change over time (p = 1, for all comparison). The BV (p = 0.50) and the BMD (p = 0.37) in the defect as measured by microCT scan during ex vivo analysis was not significantly different between DEF-CT and DEF-SHAM. Similarly, histomorphometry showed no significant difference in the total bone area (p = 0.22) and percentage bone within the defect (p = 0.24) between these groups.Bone marrow analysis of the left (radiated) and right (non-radiated) radius of the INT-CT group via a Colony Forming Units (CFU) assay demonstrated an average of 25.3 and 28.5 colonies for radiated and non-radiated radii, respectively (p = 0.72).In conclusion, there was no significant difference in bone healing between radiated and non-radiated radius defects in rabbits. This is an important finding as it demonstrates that serial in vivo high resolution-CT imaging can not only provide accurate tissue regeneration data, but it can also be used to reduce the number of temporal cohorts within an experimental design.     

Helical computed tomography alone compared with plain radiographs with adjunct computed tomography to evaluate the cervical spine after high-energy trauma

BACKGROUND: Current literature supports the use of the three-view plain-radiograph series supplemented, when necessary, with helical computed tomography to evaluate the cervical spine in patients who have sustained trauma injury. The purpose of this study was to determine if helical computed tomography alone can be used to evaluate the cervical spine for acute osseous injury following high-energy trauma, thus eliminating the need to make radiographs. METHODS: Patients were prospectively evaluated with helical computed tomography scanning of the cervical spine and standard three-view plain radiography. At a later date, the plain radiographs and computed tomography scans were independently reviewed by two radiologists who were blinded to both the initial interpretation and the interpretation of the corresponding study. The radiologists documented whether the plain radiographs were adequate and whether they showed an acute process. The findings in the study were compared with the initial findings and, when necessary, with the discharge summaries to determine if an injury had been identified. The accuracy of the plain radiographs, of the plain radiographs that had been deemed adequate, and of helical computed tomography used alone was ascertained. RESULTS: Plain radiographs and helical computed tomography scans were made for 407 patients, and traumatic injuries were identified in fifty-eight of them. Plain radiographs alone were adequate for 194 (48%) of the 407 patients. Plain radiographs had a sensitivity of 45%, a specificity of 97%, a positive predictive value of 74%, and a negative predictive value of 91%. Adequate plain radiographs had a sensitivity of 52%, a specificity of 98%, a positive predictive value of 81%, and a negative predictive value of 93%. Helical computed tomography had a sensitivity and specificity of 98%, a positive predictive value of 89%, and a negative predictive value of >99%. The sensitivity, positive predictive value, and negative predictive value of adequate plain radiographs differed significantly from those of helical computed tomography alone (p < 0.001). Twelve (48%) of twenty-five adequate plain radiographs of patients in whom an injury had been identified on computed tomography missed that injury. Helical computed tomography alone missed one (2%) of the fifty-eight injuries. CONCLUSIONS: Although helical computed tomography has a limited ability to detect pure ligamentous injury, it can be safely used without plain radiographs to evaluate the cervical spine for osseous abnormalities such as fractures and dislocations after high-energy trauma.     

涂层双相陶瓷复合BMSC修复骨缺损的实验观察

目的比较双相陶瓷（Biphasie calcium phosphate，BCP）经低结晶羟基磷灰石（Low crystalline hydroxyapatite，LcHA）涂覆改性后构建的组织工程化骨（LcBCP）与单纯BCP复合骨髓基质干细胞（Bone marrow stromal cells，BMSCs）修复兔桡骨节段性缺损的成骨差异。方法BMSCs复合LcBCP（实验组）修复12只兔左侧桡骨15mm缺损；BMSCs复合BCP（对照组）植入右侧桡骨同样大小缺损，植入后第4、8和12周取材，通过大体形态、组织学、影像学和生物力学检测骨缺损修复效果。结果BMSCs—LcBCP复合物在体内骨缺损处生长良好。X线检测显示实验组连接处骨痂形成，对照组连接处在各个时间点愈合稍差。12周时，实验组骨修复良好，髓腔再通，组织学显示板层骨形成，连接处骨性愈合；对照组连接处尚有较多编织骨形成。实验组和对照组生物力学检测有统计学差异。结论BMSCs—LcBCP复合物可修复兔桡骨节段性缺损，低品态羟基磷灰石涂层有助于增强双相陶瓷的成骨能力。     

Single-photon emission computed tomography combined with computed tomography (SPECT/CT) in bone diseases

Radionuclide bone scanning was proven effective many years ago. Its main advantages are good sensitivity, limited radiation exposure, and noninvasiveness. However, increased radionuclide uptake by a lesion is not specific, and differentiating malignant from nonmalignant disorders may therefore be difficult. An additional structural imaging study is often needed to establish the final diagnosis. Furthermore, the limited resolution of radionuclide bone scanning images does not allow accurate localization of the lesions. Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) provides both structural and functional information. SPECT/CT has been proven useful for interpreting radionuclide bone scan results in patients with bone malignancies, showing far better specificity than planar imaging or SPECT alone, most notably in the evaluation of spinal abnormalities. SPECT/CT provides an accurate evaluation of the site of the lesions and also supplies other information that can be useful in nonmalignant conditions such as injuries, infections, and degenerative disease. Nevertheless, there are only a few published studies on the usefulness of SPECT/CT in nonmalignant conditions. However, SPECT/CT is only starting to become available and may become a routine investigation for a number of rheumatic disorders.     

Sclerostin antibody stimulates bone regeneration after experimental periodontitis

The reconstruction of large osseous defects due to periodontitis is a challenge in regenerative therapy. Sclerostin, secreted by osteocytes, is a key physiological inhibitor of osteogenesis. Pharmacologic inhibition of sclerostin using sclerostin‐neutralizing monoclonal antibody (Scl‐Ab) thus increases bone formation, bone mass and bone strength in models of osteopenia and fracture repair. This study assessed the therapeutic potential of Scl‐Ab to stimulate alveolar bone regeneration following experimental periodontitis (EP). Ligature‐induced EP was induced in rats to generate localized alveolar bone defects. Following 4 weeks of disease induction, Scl‐Ab (+EP) or vehicle (+/? EP) were systemically delivered, twice weekly for up to 6 wks to determine the ability of Scl‐Ab to regenerate bone around tooth‐supporting osseous defects. 3 and 6 wks after the initiation of Scl‐Ab or vehicle treatment, femur and maxillary jawbones were harvested for histology, histomorphometry, and micro‐computed tomography (micro‐CT) of linear alveolar bone loss (ABL) and volumetric measures of bone support, including bone volume fraction (BVF) and tissue mineral density (TMD). Serum was analyzed to examine bone turnover markers during disease and regenerative therapy. Vehicle + EP animals exhibited maxillary bone loss (BVF, TMD and ABL) at ligature removal and thereafter. 6 weeks of Scl‐Ab significantly improved maxillary bone healing, as measured by BVF, TMD and ABL, when compared to vehicle + EP. After 6 weeks of treatment, BVF and TMD values in the Scl‐Ab + EP group were similar to those of healthy controls. Serum analysis demonstrated higher levels of bone formation markers osteocalcin and PINP in Scl‐Ab treatment groups. Scl‐Ab restored alveolar bone mass following experimental periodontitis. These findings warrant further exploration of Scl‐Ab therapy in this and other oral bone defect disease scenarios. © 2013 American Society for Bone and Mineral Research.     

局部植入辛伐他汀诱导自体骨髓间充质干细胞归巢修复大鼠颅骨缺损

目的探讨局部植入辛伐他汀修复大鼠颅骨极限骨缺损的机制,即诱导自体骨髓间充质干细胞（BMSC）归巢。方法辛伐他汀5mg加聚乳酸20mg或单纯聚乳酸20mg分别溶解于200μl丙酮,制备辛伐他汀聚乳酸复合材料或单纯聚乳酸材料。16只SD大鼠尾静脉注射绿色荧光蛋白（GFP）标记的BMSC（GFP-BMSC）作为示踪细胞,48h后制作大鼠颅骨极限缺损模型,并植入辛伐他汀-聚乳酸复合材料（n=8）和单纯聚乳酸材料（n=8）进行修复。2周后经小动物活体荧光成像系统检测缺损处绿色荧光信号,冰冻切片荧光显微镜下观察辛伐他汀组（n=4）和对照组（n=4）缺损处GFP-BMSC归巢。颅骨脱钙后经免疫组化染色检测辛伐他汀组（n=4）和对照组（n=4）缺损处骨形态发生蛋白-2（BMP-2）表达。结果小动物活体荧光成像系统检测显示,辛伐他汀组缺损处有较强的绿色荧光信号,对照组缺损处绿色荧光信号较弱;冰冻切片荧光显微镜下观察发现,辛伐他汀组缺损处较对照组缺损处GFP阳性细胞数量明显增加;免疫组化检测发现,辛伐他汀组BMP-2表达增加。结论局部植入辛伐他汀可诱导自体BMSC归巢至缺损部位并参与修复,其诱导归巢过程可能与BMP-2表达上调有关。     

Reliability of plain X-ray and computed tomography in diagnosis of invasive tumors of the scalp

Summary The reliability of plain X-ray and computed tomography (CT) in the diagnosis of a penetrating tumor of the scalp to the calvarium was examined on the basis of the histopathologic reports following surgery. The correlation of other tumor characteristics, such as size, ulceration, duration and previous excisions or irradiation to the skull, with calvarial invasion was also studied. Of the 29 scalp tumors suspected clinically of invasion, four were proven histopathologically as penetrating to the bone. Only two of the four tumors diagnosed by plain X-ray of the skull as penetrating to the bone, and two of the six so diagnosed by CT, were histopathologically substantiated. No statistical correlation was found between the radiologic reports and the histopathology relating to the diagnosis of calvarial invasion by scalp tumor. The other tumor characteristics also did not correlate statistically with invasion. We conclude that the radiologic reports of plain X-ray and CT concerning penetration to the calvarium by scalp tumor are not reliable. In addition, there are no other tumor characteristics that correlate with histopathological penetration.