Metaphyseal fracture healing follows similar biomechanical rules as diaphyseal healing

It is generally supposed that the pattern of fracture healing in trabecular metaphyseal bone differs from that of diaphyseal fractures. However, few experimental studies to date have been performed, even though clinically many fractures occur in metaphyseal bone. Particularly, the influence of biomechanical factors has not yet been investigated under standardized conditions. Our aim was to correlate the interfragmentary strain (IFS) with the bone‐healing outcome in a controlled metaphyseal fracture model in sheep. Twelve sheep received a partial osteotomy in the distal femoral condyle close to the trochlea. The determination of the IFS by in vivo X‐ray analyses and a finite element model revealed that the deflection of the osteotomy gap by the patello‐femoral force during walking provoked increasing strains of up to 40%. Bone healing was evaluated after 8 weeks by the assessment of the bone mineral density and by histomorphometry in regions of interest that displayed differing magnitudes of IFS. In areas with strains below 5% significantly less bone formation occurred compared to areas with higher strains (6–20%). For strains larger than 20% fibrocartilage layers were observed. Low IFS (<5%) led to intramembranous bone formation, whereas higher strains additionally provoked endochondral ossification or fibrocartilage formation. It is therefore proposed that metaphyseal bone healing follows similar biomechanical principles as diaphyseal healing. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:425–432, 2011     

Serum type I procollagen peptide: a non-invasive index of bone formation in patients on haemodialysis?

The value of serum procollagen peptide (PICP) as a non-invasiveindex of bone formation was studied in 18 patients establishedon haemodialysis. There was a significant correlation betweenPICP and serum alkaline phosphatase activity (ALP; r=0.55, P<0.05),and between PICP and osteocalcin (r=0.53, P<0.05). PICP alsocorrelated significantly with histomorphometric indices of boneformation, particularly bone formation rates (BFR) as estimatedby the tetracycline double-labelled technique (r=0.74, P<0.01),but not with those of bone resorption. There was a similar relationshipbetween BFR and ALP. From the regression analyses, a normalBFR was associated with normal PICP values despite the absenceof renal function, suggesting that the impact of renal functionon serum concentrations of PICP may not be large. Seven patientshad histochemical evidence for significant aluminium overload.th these patients the expected sup pression in biochemical andhistological indices of bone formation was associated with inappropriatelyraised PICP concentrations. The mechanism of this discrepancyis not clear, but caution is advocated in the interpretationof PICP in the presence of significant aluminium overload. Ourfindings otherwise suggest that PICP may be a useful non-invasiveindex of bone formation in patients on haemodialysis.     

Bone debridement and limb lengthening in type III open tibial shaft fractures: No infection or nonunion in 9 patients

We retrospectively reviewed a consecutive series of 9 patients with tibial shaft fractures and extensive soft tissue damage, who had completed treatment by means of bone resection and distraction. 4 patients had type IIIB fractures and 5 type IIIC. The median follow-up time after bone resection was 27 (12-43) months. All patients were treated with debridement of devitalized soft tissue and resection of dead bone at the fracture site. The median bone shortening was 4 (3-9) cm. Equal limb-length was restored by proximal corticotomy and lengthening. A free vascular flap in 5 patients and a local flap in 4 patients corrected the soft tissue loss. All soft tissue transfers were successful, except in 1 case, which healed after a new free flap was made. The median union time of the fracture was 8 (4.5-28) months from the injury and 7 (3-10) months from the time of bone resection. There were no deep infections or nonunions and no secondary amputations. This series shows that bone debridement and limb lengthening, with a multidisciplinary approach, is often successful in salvaging limbs at high risk of amputation.     

Evaluation of Breast Fat by Preoperative Mammography, Histology, and Thermal Extraction of Surgical Specimens

Abstract: The fat contained in the breasts of 33 unselected patients submitted to breast-reduction procedures was studied by three methods: preoperative mammography, histological examination of samples from the surgical specimens, and thermal fat extraction from these specimens. The 3 methods showed that the majority of the patients have more than half of their breast tissues constituted by fat. Thermal extraction produced the most accurate data, as the results could be measured instead of evaluated grossly. It showed a mean amount of 48% of breast fat with extreme variations from 2% to 78%. It also revealed major variations among patients of the same age and aspect. These variations were not detectable by clinical examination, and hardly predicted by mammography. The microscopical study showed that the whitish parts of the breast, which surgeons consider as “fibroglandular” tissue, do not contain more epithelial components than the fatty parts. These observations, like those on breast fat, are new. Their consequences, as concerns lactation, evolution of the breast with time, breast-surgery techniques, and surgical complications, have yet to be evaluated.     

Chordoma: A Clinicopathologic and Prognostic Study of a Swedish National Series

Chordoma is a rare tumor with slow growth developing from remnants of the notochord and thus appears in close relation to the axial skeleton. A Swedish national series collected over a period of 13 years, comprising 51 patients with a follow-up time of 8-20 years, was studied. Histologically all tumors had a typical appearance except two, which had the characteristics of “chondroid chordoma”. Fifty-seven per cent of the tumors were located in the sacrococcygeal region, 27 per cent in the spheno-occipital region and 16 per cent in the vertebrae. The peak age incidence was in the 6th and 7th decades. Male: female ratio was 1:1. The main symptoms were pain and neurologic disturbances. Skeletal destruction was noted radiographically in most instances. Intratumoral calcifications were rarely seen. The treatment was surgery, radiotherapy or a combination of these. There was only one long-term survivor without evidence of disease, a patient operated on for cervical chordoma 14 years earlier. Six other patients lived 8-18 years after diagnosis with chordoma. All other patients were dead; 39 died of chordoma, five of unrelated causes. Distant metastases were noted in 29 per cent. Chordoma constituted 17.5 per cent of all primary malignant bone tumors of the axial skeleton. The yearly incidence was 0.51 per million inhabitants in Sweden.     

Bone histology in steroid-treated children with non-azotemic nephrotic syndrome

Patients with nephrotic syndrome (NS) and normal glomerular filtration rate (GFR) frequently exhibit abnormalities of calcium and vitamin D homeostasis, mainly hypocalcemia and reduced circulating vitamin D metabolites. These abnormalities have been linked to alterations of bone histology in adults with non-azotemic NS, particularly osteomalacia and excessive bone resorption. Whether similar abnormalities of bone histology occur in children and adolescents with NS, particularly in those requiring prolonged treatment with corticosteroids, remains largely unknown. Thus, bone histomorphometry and selected bone-modulating hormones were studied in eight children (aged 2–16 years) with normal GFR (range 85–169 ml/min per 1.73 m²) and NS. All patients received corticosteroids for at least 12 months prior to bone biopsy. At the time of bone biopsy, the urine protein/creatinine ratio was elevated (2.1±3.6), while the average concentrations of parathyroid hormone (36±13 pg/ml), 25-hydroxyvitamin D [25(OH) D] (22±14 ng/ml), and 1,25(OH)₂D (59±22 pg/ml) were normal. Bone histomorphometry displayed focal osteomalacia (OM) and mild increased bone resorption in most patients. The mineralization lag time, an indicator of the degree of osteomalacia, correlated with the time elapsed since the original diagnosis of NS (r=0.93, P<0.0005). Overt hyperparathyroidism was not evident, but increased eroded perimeter and elevated bone formation rate (BFR) were evident in two patients, suggesting high-turnover bone disease. The BFR was inversely correlated with the administered dose of prednisone at the time of biopsy (r=–0.78, P<0.05) and one patient exhibited low bone turnover changes. The growth velocity standard deviation score (SDS) at time of biopsy ranged from –1.6 to 3.2, resulting in a height SDS range of –1.9 to 0.6. The height SDS at time of bone biopsy correlated inversely with the dose of administered glucocorticoid (r=–0.71, P<0.05) and with the duration of the disease (r=–0.7, P=0.05). These data, albeit preliminary, demonstrate that children with NS treated with prolonged corticosteroid therapy exhibit bone histopathological changes without a concomitant impairment in GFR. While the OM appears to be related to the disease process, the alterations of bone formation and the adynamic changes are likely the result of the corticosteroid therapy. The potential consequences of these findings on adult bone mass and ultimate height deserve further studies.     

Chordoma in Finland

During the period 1953-1971, 20 cases of chordoma were reported to the Finnish Cancer Registry. Twelve of the patients were males. The mean annual (crude) incidence of chordoma in Finland was 0.30/10⁶ in males, and 0.18/10⁶ in females. Fifteen of the tumours were sacral, three vertebral, and two cranial. Local recurrences were common, and distant metastases were observed in 60 per cent of the cases; this exceeds the proportion usually mentioned in the literature. The commonest treatment was surgery combined with postoperative high-dose irradiation. The relative 5-year survival rate was 35 per cent, and the 10-year rate 18 per cent.     

Microvascular and histologic effect of circumferential wire on appositional bone growth in immature dogs

Circumferential wires were placed around both midshaft femora of six immature dogs. On one side the wires were placed under the periosteum and on the other side the wires were placed over the periosteum. All wires were tightened to an equivalent tension. A diffuse growth of periosteal new bone occurred in those femora in which wires were placed under the periosteum but not in those over the periosteum. Corresponding microangiographs at 3 weeks in those femora in which wires were placed under the periosteum revealed dramatically increased medullary and periosteal vascularity coupled with histologic active trabecular bone formation. In those femora in which the wires were placed over the periosteum, even though the placement of the wires should supposedly have been the most detrimental, vascularity was not restricted. There were perfused vessels within the cortex directly under the wires. At 8 weeks the wires in both preparations were becoming encased in the growing cortical bone. Cerclage did not devitalize immature bone nor did it restrict adjacent appositional bone growth.     

The Effect of Drinking Water Fluoridation on the Fluoride Content,Strength and Mineral Density of Human Bone

The effect of drinking water fluoridation on the fluoride content of human bone, on cancellous bone strength and on the mineral density of bone was studied by analysing 158 autopsy samples of the anterior iliac crest from persons from two different areas. in the samples from the town of Kuopio, where drinking water has been fluoridated since 1959, the fluoride concentrations were considerably higher than in samples from the surrounding area where low—fluoride drinking water is used. the fluoride content of bones from Kuopio increased significantly with age, while considerably less change with age was found in samples from outside Kuopio. the highest fluoride content in bone ash was observed in women with severe osteoporosis.

Cancellous bone strength measured by a strain transducer was statistically significantly higher in women with chronic immobilizing disease from Kuopio, compared with the corresponding group from outside Kuopio. No statistically significant differences in bone strength were found in men. There were no statistically significant differences in bone mineral density, as measured by gamma ray attenuation, between the samples from the fluoridated and non—fluoridated areas.     

Energy requirements for osteotomy of femora and tibiae with a moving CW CO2 laser

This paper describes the laser cutting and the amount of laser energy needed to remove a unit mass of compact or cancellous human cadaveric bones ("heat-of-removal") by using a CO2 laser. Data are collected under different operating conditions, such as laser power, scanning speed, and lens focusing for fresh and fixed human bones from male and female femora and tibiae samples with ages varying between 28 and 73 years old. The aim of the present experiments was to demonstrate the feasibility of laser osteotomy, to find the energy requirements for given groove depths or bone removal rates, and to shed some light on optimum conditions for laser osteotomy. Only cadaveric bones were used in this study, since the present aim did not include the investigation of heating rates and the extent and effect of thermal necrosis adjacent to the cut. In vivo properties may be somewhat different from those of cadaveric material. While blood circulation within the living bone may contribute to the laser cutting characteristics, it cannot be addressed here. Experiments showed that very deep cuts are difficult to achieve with a CO2 laser, as at high-power/low-scan-speed the groove becomes rather wide, with unacceptable thermal damage adjacent to the cut, while multiple passes do not easily attain large depths. There was no significant difference for the laser heat-of-removal for different age groups and for male and female samples. The laser heat-of-removal was found to be higher for compact bone than for cancellous bone samples. Comparison of cross-sections of the cuts with an existing model gave good agreement.     

Effects of in vivo mechanical loading on large bone defect regeneration

Fracture healing is highly sensitive to mechanical conditions; however, the effects of mechanical loading on large bone defect regeneration have not been evaluated. In this study, we investigated the effects of functional loading on repair of critically sized segmental bone defects. About 6-mm defects were created in rat femora, and each defect received 5 μg recombinant human bone morphogenetic protein-2 (rhBMP-2), delivered in alginate hydrogel. Limbs were stabilized by either stiff fixation plates for the duration of the study or compliant plates that allowed transfer of compressive ambulatory loads beginning at week 4. Healing was assessed by digital radiography, microcomputed tomography, mechanical testing, histology, and finite element modeling. Loading significantly increased regenerate bone volume and average polar moment of inertia. The response to loading was location-dependent with the polar moment of inertia increased at the proximal end of the defect but not the distal end. As a result, torsional stiffness was 58% higher in the compliant plate group, but failure torque was not altered. In single samples assessed for histology from each group, a qualitatively greater amount of cartilage and a lesser degree of remodeling to lamellar bone occurred in the loaded group compared to the stiff plate group. Finally, principal strain histograms, calculated by FE modeling, revealed that the compliant plate samples had adapted to more efficiently distribute loads in the defects. Together, these data demonstrate that functional transfer of axial loads alters BMP-induced large bone defect repair by increasing the amount and distribution of bone formed within the defect.     

A preclinical study of stem subsidence and graft incorporation after femoral impaction grafting using porous hydroxyapatite as a bone graft extender

This preclinical in vivo screening study compared bone graft incorporation and stem subsidence in cemented hemiarthroplasty after femoral impaction bone grafting with either morselized allograft bone (n = 5, control group) or a 1:1 mix of allograft and porous hydroxyapatite ceramics (HA) granules (n = 5, HA group). At 14 weeks, there was excellent bone graft incorporation by bone, and the stems were well fixed in both groups. The median subsidence at the cement-bone interface, measured using radiostereometric analysis, was 0.14 and 0.93 mm in the control and HA groups, respectively. The comparable histologic results between groups and good stem fixation in this study support the conduct of a larger scale investigation of the use of porous HA in femoral impaction bone grafting at revision hip arthroplasty.     

前列腺癌患者10号染色体杂合性缺失与骨转移关系的初步研究

目的:探讨人前列腺癌特异性骨转移的细胞遗传学机制。方法:应用比较基因组杂交技术对18例前列腺癌患者进行染色体变异情况的初步分析,确定可能与骨转移密切相关的变异染色体。再应用PCR及微卫星多态性技术重点对10号染色体上的7个微卫星位点进行杂合性缺失(LOH)检测。结果:11例伴有远处骨转移的患者组织样本中,10号染色体的变异率为90.9%(10/11),显著高于其他染色体(P<0.01);进一步分析发现,7个微卫星位点的LOH现象中,骨转移患者的发生率最高,且以D10S1693～D10S587(10q24.2～q25.3)区的LOH发生率最高。结论:10号染色体上D10S1693～D10S587区(10q24.2～q25.3)是前列腺癌骨转移患者中一个高频的LOH区,此区可能与前列腺癌患者远处骨转移的发生密切相关。     

Correlation of nipple aspiration and ductal lavage cytology with histopathologic findings for patients before scheduled breast biopsy examination

BACKGROUND: The use of ductal lavage to obtain cells from within the breast ducts has been described for patients at high risk for breast cancer. The purpose of this study was to correlate ductal lavage cytologic findings with the corresponding histology. METHODS: Twenty-two patients were evaluated and 20 patients underwent ductal lavage followed by breast biopsy examination as a result of positive nipple aspiration fluid. Ductal lavage samples were classified by a cytopathologist as negative, mild atypia, marked atypia, or malignant. A different pathologist interpreted the histologic findings of the biopsy examination. RESULTS: Adequate specimens for cellularity were obtained in 12 of 22 (53%) patients: 6 of the 12 (50%) had both benign cytology and histology, 2 (16.7%) had benign cytology with atypical ductal hyperplasia or atypical lobular hyperplasia on histology, 2 (16.7%) had marked atypia on cytology and benign histology, and 2 (16.7%) had malignant cytology and benign histology. The specificity of the procedure was 83.4%. CONCLUSIONS: Ductal lavage yielding an adequate sample for analysis was successful in only 52% of patients. Of those, the cytologic-histologic correlation was discordant in 50%. The role of ductal lavage in accurately predicting lesions present on subsequent breast histologic evaluation of planned biopsy examinations requires further investigation.     

CD-147在骨肉瘤中的表达及其与临床病理指标的相关性实验研究

[目的]验证CD-147在骨肉瘤组织中的表达及与临床病理指标的相关性.[方法]SABC法免疫组化分析55例骨肉瘤组织中CD-147基因的表达,并对其与骨肉瘤临床病理的关系进行统计学分析.[结果]作者的研究提示CD-147基因在骨肉瘤组织有高表达,并且与其外科分级具有明显相关性.[结论]骨肉瘤CD-147蛋白的表达与肿瘤恶性程度密切相关,对骨肉瘤诊断和预后评估具有重要价值.     

Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease?

In an uncontrolled open study 13 patients with moderate to preterminalrenal failure were treated with low doses (average 0.36 µg/day)of calcitriol up to the time of renal transplantation, whichwas performed before dialysis had been initiated. A transiliacbone biopsy was obtained both at the start and at the end ofthe treatment period, the latter coinciding with renal transplantation.All patients who started calcitriol treatment at a creatinineclearance (C_cr) above 30 ml/min had normal bone histology atthe time of transplantation, but this was not observed whencalcitriol treatment was started at C_cr below 30 ml/min. The study suggests that full benefit of calcitriol at the bonelevel is obtained only if prophylactic administration is startedearly in the course of renal failure.     

异种脱蛋白松质骨为载体构建组织工程骨用于脊柱横突间融合的实验观察

目的探讨异种脱蛋白松质骨（deproteinization bone,DPB）作为骨组织工程载体的性能及其用于山羊脊柱横突间融合的作用。方法取成年猪股骨远端松质骨通过理化方法制成DPB载体,对其形态结构、组成成分、生物力学特性以及材料对种子细胞生物学行为的影响进行检测分析。将载体材料复合一定量的自体骨髓间充质干细胞（mesenchymal stem cells,MSCs）重组人骨形成蛋白2（recombinant human bone morphogenetic protein 2,rhBMP-2）构建组织工程骨。取6～8月龄雄性山羊12只,制成L3-4双侧横突间植骨模型,左侧植入组织工程骨为A组,右侧植入等体积自体髂骨作对照为B组。分别于4、8及12周行X线片和组织学观察并对比分析。结果采用脱蛋白处理后的松质骨可见大小不等、相互交通、开放孔隙的网架结构。孔径200～500μm,孔隙率60％左右。其无机成分为羟基磷灰石,有机成分为胶原,力学性能保存良好,有良好的细胞相容性。两组移植后不同时间点X线表现：A组植入横突间第4周与横突桥接处部分区域模糊,以内侧明显;第8周上下桥接部间隙变小,大量连续骨痂生成;12周后完全融合。早期A组密度略低于B组,12周后基本相同。移植区组织学观察：A组植入后第4周以多点方式形成新骨,第8周岛状生长的骨组织贯穿整个移植材料,12周编织骨交错排列,髓腔形成,成骨活性接近自体髂骨移植。B组,4周时有较多新骨形成;8周时出现大量胶原纤维,周边成骨明显;12周时,纤维组织减少,成骨活跃。结论异种DPB是一种良好的组织工程骨载体材料,可为再血管化和成骨细胞的分化提供一个稳定的环境。     

DNA-Analysis of Human Testicular Samples by Cytofluorometry

Germ cells in human testicular samples have been estimated by histology and quantitated by flow cytometry. There is an excellent relationship between the two techniques. These samples were classified histologically as "normal", "reduced number of germ cells" or "no germ cells". A definition of "normalcy" as determined by flow cytometry as having at least 38% of the cells in the haploid state, is proposed. Testicular samples from prepubertal boys with infiltrating leukemic cells often show an increase in the percentage of S-phase cells indicating the presence of tumor. These results indicate the value of flow cytometry in the identification of reproductive and neoplastic disorders.     

Tendon to bone tunnel healing—A study on the time‐dependent changes in biomechanics,bone remodeling,and histology in a rat model

Tendons and ligaments attach to bone through a transitional connective tissue with complex biomechanical properties. This unique tissue is not regenerated during healing, and surgical reattachment therefore often fails. The present study was designed to evaluate tendon healing in a bone tunnel and to evaluate the utilized rat model. Wistar rats (n = 61) were operated with the Achilles tendon through a bone tunnel in the distal tibia. Healing was evaluated at 2, 3, 4, and 12 weeks by biomechanical testing, bone mineral density and histology. After 2 weeks median (interquartile range) pull‐out force was 2.2 N (1.9). The pull‐out force increased chronologically, by 12 weeks fivefold to 11.2 N (11.4). Energy absorption, stiffness, and bone mineral density increased similarly. The histological analyses showed inflammation at early stages with increasing callus by time. Our data showed a slow healing response the first 4 weeks followed by an accelerated healing period, favoring that most of the gain in mechanical strength occurred later than 4 weeks postoperatively. These findings support the concern of a vulnerable tendon bone tunnel interface in the early stages of healing. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:216–223, 2015.