Cumulative Effects of Bone and Soft Tissue Injury on Systemic Inflammation: A Pilot Study

Background

In multiply injured patients, bilateral femur fractures invoke a substantial systemic inflammatory impact and remote organ dysfunction. However, it is unclear whether isolated bone or soft tissue injury contributes to the systemic inflammatory response and organ injury after fracture.

Questions/purposes

We therefore asked whether the systemic inflammatory response and remote organ dysfunction are attributable to the bone fragment injection, adjacent soft tissue injury, or both.

Methods

Male C57/BL6 mice (8–10 weeks old, 20–30 g) were assigned to four groups: bone fragment injection (BF, n = 9) group; soft tissue injury (STI, n = 9) group; BF + STI (n = 9) group, in which both insults were applied; and control group, in which neither insult was applied. Animals were sacrificed at 6 hours. As surrogates for systemic inflammation, we measured serum IL-6, IL-10, osteopontin, and alanine aminotransferase (ALT) and nuclear factor (NF)-κB and myeloperoxidase (MPO) in the lung.

Results

The systemic inflammatory response (mean IL-6 level) was similar in the BF (61.8 pg/mL) and STI (67.9 pg/mL) groups. The combination (BF + STI) of both traumatic insults induced an increase in mean levels of inflammatory parameters (IL-6: 189.1 pg/mL) but not in MPO levels (1.21 ng/mL) as compared with the BF (0.82 ng/mL) and STI (1.26 ng/mL) groups. The model produced little evidence of remote organ inflammation.

Conclusions

Our findings suggest both bone and soft tissue injury are required to induce systemic changes. The absence of remote organ inflammation suggests further fracture-associated factors, such as hemorrhage and fat liberation, may be more critical for induction of remote organ damage.

Clinical Relevance

Both bone and soft tissue injuries contribute to the systemic inflammatory response.     

Distribution of Locally Delivered Antimicrobials Is Limited by Cortical Bone: A Pilot Study

Background

Local delivery is required to achieve the high antimicrobial concentrations needed to treat biofilm-forming infections. The delivery site is commonly either in the intramedullary canal or at the periosteal surface. It is unknown whether locally delivered antimicrobials are transported transcortically between the endosteal and periosteal surfaces when the infection involves the opposite surface.

Questions/Purposes

(1) Are antimicrobials transported transcortically between the endosteal and periosteal surfaces over time? And (2) are transcortical antimicrobials transported uniformly over the cortical surface?

Methods

To study transcortical antimicrobial transport, 12 human cadaveric femoral segments obtained from two women aged 63 and 64 years and one man aged 64 years were filled with antimicrobials. Three diaphyseal segments were filled with 5 wt% vancomycin in an N-isopropylacrylamide-based hydrogel and eluted in phosphate-buffered saline under infinite-sink conditions for 5 days; vancomycin was assayed by high-performance liquid chromatography. Nine segments (three infraisthmal diaphysis, three metaphysis, three epiphysis) embedded in 0.1% agarose gel were filled with aqueous doxycycline (400 μg/mL) and imaged under ultraviolet light for fluorescence on the periosteal surface at 15-minute intervals for 3 days.

Results

Transcortical vancomycin elution occurred: 8.65 mg during Day 1 and 26.5 mg by Day 5. Fluorescence from transcortical doxycycline transport was only visualized at focal locations corresponding to vascular foramina, appearing first at 5 to 10 minutes, with none over the majority of the periosteal surface for up to 24 hours.

Conclusions

Transcortical transport of locally delivered antimicrobials occurs primarily through vascular foramina.

Clinical Relevance

Transcortical antimicrobial transported may not be adequate to achieve therapeutic levels for infection on the far side of an intact cortex.     

Percutaneous Radiofrequency Epiphysiodesis in a Rabbit Model: A Pilot Study

Background

Techniques for epiphysiodesis have evolved from open surgical techniques requiring direct observation of the physis to percutaneous techniques performed with fluoroscopy.

Questions/purposes

Our purposes were to (1) describe a new minimally invasive surgical technique used to achieve epiphysiodesis using radiofrequency ablation, (2) document the effect of radiofrequency ablation on tibia length at 2, 6, and 12 weeks after ablation in a skeletally immature rabbit model, and (3) assess the effects of radiofrequency ablation on the histologic appearance of the proximal tibia physis and proximal tibia articular cartilage.

Materials and Methods

We performed epiphysiodesis of the rabbit proximal tibia on 15 skeletally immature male New Zealand White rabbits using a 22-gauge radiofrequency probe. The probe was positioned percutaneously and heated to 90°C for 4 minutes on the medial and lateral ½ of the physis. The opposite tibia was used as a control. Five animals were sacrificed at 2, 6, or 12 weeks postoperatively. Tibia length was compared using Faxitron® radiographs and electronic calipers. Histology of the growth plate was assessed with light microscopy.

Results

We observed differences in tibia length between 4.16 mm and 11.59 mm (average 7.86 mm) at 12 weeks. The proximal tibia physis closed radiographically and histologically in all animals by 12 weeks. Histologic analysis showed no evidence of articular cartilage injury.

Conclusions

This technique was reproducible and resulted in bone fusion of the rabbit proximal tibial growth plate. The use of radiofrequency ablation as described in this report may be used as an alternative to other surgical epiphysiodesis techniques.

Clinical Relevance

This technique may be useful for epiphysiodesis of small tubular bones of the hands and feet in humans.     

Ultrasound-Based Estimates of Cortical Bone Thickness and Porosity Are Associated With Nontraumatic Fractures in Postmenopausal Women: A Pilot Study

Recent ultrasound (US) axial transmission techniques exploit the multimode waveguide response of long bones to yield estimates of cortical bone structure characteristics. This pilot cross-sectional study aimed to evaluate the performance at the one-third distal radius of a bidirectional axial transmission technique (BDAT) to discriminate between fractured and nonfractured postmenopausal women. Cortical thickness (Ct.Th) and porosity (Ct.Po) estimates were obtained for 201 postmenopausal women: 109 were nonfractured (62.6 ± 7.8 years), 92 with one or more nontraumatic fractures (68.8 ± 9.2 years), 17 with hip fractures (66.1 ± 10.3 years), 32 with vertebral fractures (72.4 ± 7.9 years), and 17 with wrist fractures (67.8 ± 9.6 years). The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. Femoral aBMD correlated weakly, but significantly with Ct.Th (R = 0.23, p < 0.001) and Ct.Po (R = -0.15, p < 0.05). Femoral aBMD and both US parameters were significantly different between the subgroup of all nontraumatic fractures combined and the control group (p < 0.05). The main findings were that (1) Ct.Po was discriminant for all nontraumatic fractures combined (OR = 1.39; area under the receiver operating characteristic curve [AUC] equal to 0.71), for vertebral (OR = 1.96; AUC = 0.84) and wrist fractures (OR = 1.80; AUC = 0.71), whereas Ct.Th was discriminant for hip fractures only (OR = 2.01; AUC = 0.72); there was a significant association (2) between increased Ct.Po and vertebral and wrist fractures when these fractures were not associated with any measured aBMD variables; (3) between increased Ct.Po and all nontraumatic fractures combined independently of aBMD neck; and (4) between decreased Ct.Th and hip fractures independently of aBMD femur. BDAT variables showed comparable performance to that of aBMD neck with all types of fractures (OR = 1.48; AUC = 0.72) and that of aBMD femur with hip fractures (OR = 2.21; AUC = 0.70). If these results are confirmed in prospective studies, cortical BDAT measurements may be considered useful for assessing fracture risk in postmenopausal women. © 2019 American Society for Bone and Mineral Research.     

Changes in Bone Marrow Adipose Tissue in Transgender and Gender Non-Conforming Youth Undergoing Pubertal Suppression: A Pilot Study

Pubertal suppression with gonadotropin-releasing hormone (GnRH) agonists in transgender and gender non-conforming (TGNC) youth may affect acquisition of peak bone mass. Bone marrow adipose tissue (BMAT) has an inverse relationship with bone mineral density (BMD). To evaluate the effect of pubertal suppression on BMAT, in this pilot study we prospectively studied TGNC youth undergoing pubertal suppression and cisgender control participants with similar pubertal status over a 12-month period. BMD was measured by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Magnetic Resonance T1 relaxometry (T1-R) and spectroscopy (MRS) were performed to quantify BMAT at the distal femur. We compared the change in BMD, T1-R values, and MRS lipid indices between the two groups. Six TGNC (two assigned female and four assigned male at birth) and three female control participants (mean age 10.9 and 11.7 years, respectively) were enrolled. The mean lumbar spine BMD Z-score declined by 0.29 in the TGNC group, but increased by 0.48 in controls (between-group difference 0.77, 95% CI: 0.05, 1.45). Similar findings were observed with the change in trabecular volumetric BMD at the 3% tibia site (-4.1% in TGNC, +3.2% in controls, between-group difference 7.3%, 95% CI: 0.5%-14%). Distal femur T1 values declined (indicative of increased BMAT) by 7.9% in the TGNC group, but increased by 2.1% in controls (between-group difference 10%, 95% CI: -12.7%, 32.6%). Marrow lipid fraction by MRS increased by 8.4% in the TGNC group, but declined by 0.1% in controls (between-group difference 8.5%, 95% CI: -50.2%, 33.0%). In conclusion, we observed lower bone mass acquisition and greater increases in BMAT indices by MRI and MRS in TGNC youth after 12 months of GnRH agonists compared with control participants. Early changes in BMAT may underlie an alteration in bone mass acquisition with pubertal suppression, including alterations in mesenchymal stem cells within marrow.     

Distinctive Head and Neck Bone and Soft Tissue Neoplasms

Benign and malignant primary bone and soft tissue lesions of the head and neck are rare. The uncommon nature of these tumors, combined with the complex anatomy of the head and neck, pose diagnostic challenges to pathologists. This article describes the pertinent clinical, radiographic, and pathologic features of selected bone and soft tissue tumors involving the head and neck region, including angiofibroma, glomangiopericytoma, rhabdomyosarcoma, biphenotypic sinonasal sarcoma, chordoma, chondrosarcoma, and osteosarcoma. Emphasis is placed on key diagnostic pitfalls, differential diagnosis, and the importance of correlating clinical and radiographic information, particularly for tumors involving bone.     

骨段滑移术治疗胫骨缺损合并软组织缺损

目的总结骨段滑移术治疗胫骨长节段骨缺损合并小腿软组织缺损的疗效、适应证及术后康复在促进功能恢复中的作用。方法在2005年1月到2011年1月6年间治疗胫骨长节段性骨缺损合并小腿软组织缺损共13例,男性10例,女性3例;年龄16～35岁,平均24岁。胫骨缺损部位在胫骨中下段11例,在胫骨中上段2例。缺损长度7～15cm,平均9cm。软组织缺损位于小腿的前内侧,范围3cm×2cm～18cm×10cm。采用Orthofix重建外固定架,一期截骨,7d后开始延长,每日1mm,到胫骨远近缺损骨端紧密对合,维持固定直至骨愈合。小腿软组织缺损感染重、渗出多者使用负压封闭引流技术。术后进行康复治疗。结果从开始治疗到去除外固定架,治疗用时11～23个月,平均18个月。13例胫骨骨缺损获得重建,患肢肢体长度与健侧相差小于2cm,截骨延长新生骨部分愈合良好。11例骨缺损接触端自行愈合,有2例骨折断端软组织内陷阻止骨端接触,1例采用软组织松解,1例行软组织松解加自体植骨术。创面均得到覆盖。闭合的创面部分凹陷为贴骨瘢痕,遇阴雨天不适。骨段滑移过程中在牵开3cm左右时患者感到小腿疼痛,对症治疗后大多可继续进行延长,有4例停止延长3～5d后继续延长直至完成。外固定架未出现固定钉明显松动现象,中间2枚固定钉在滑移的中后期有不同程度的对皮肤切割现象,将皮肤钉孔拉成椭圆形,此钉孔在骨段滑移停止后3周左右恢复正常。所有患者膝关节活动正常,踝关节背伸活动可达15°～30°。结论骨段滑移术是治疗胫骨长节段骨缺损合并软组织缺损的一种较好的方法,最适合的病例是胫骨中上段或中下段长节段骨缺损合并软组织缺损,胫骨近端和远端有置入固定钉的足够长度,腓骨完整性较好的患者。结合康复治疗可使伤残肢体功能最大限度地恢复。     

异种脱蛋白皮质骨管复合组织工程骨修复大段骨缺损的实验研究

目的评估异种脱蛋白皮质骨管复合组织工程骨修复大段骨缺损的力学作用及成骨效果。方法 36只成年猪,随机分成3组,实验组植入异种脱蛋白皮质骨管复合骨基质明胶、骨形态发生蛋白及骨膜细胞,对照组植入异种脱蛋白骨皮质骨管复合自体髂骨微粒,空白对照组植入单纯异种脱蛋白骨管,三组均采用锁定钢板及异种皮质骨板固定。通过X线检查、病理组织学、生物力学及灰量测定检查观察骨缺损修复情况。结果术后24周,实验组及对照组骨缺损处新生骨生长良好,骨小梁排列整齐,空白对照组骨缺损新生骨较少,且与断端部分相连。植入后24周实验组与对照组的生物力学及骨矿含量相比无统计学差异,且均明显高于空白对照组。结论异种脱蛋白皮质骨管复合骨基质明胶、骨形态发生蛋白及骨膜细胞修复大段骨缺损具有良好的应力支撑作用,其成骨效果与自体松质骨相当。     

Soft and Hard Tissue Changes Following Treatment of Class II Division 1 Malocclusion with Twin-Block and Myofunctional Appliance: A Pilot Study

BackgroundMany cases of Class II deformities have been reported to be treated with prefabricated appliances. The aim of this study was to distinguish the clinical effect of traditional custom-made appliances and prefabricated appliances in the treatment of Class II division 1 malocclusion. Therefore, soft and hard tissue changes following treatment of Class II division 1 malocclusion using the twin-block (TB) appliance was compared to that using the Myofunctional Research Company (MRC) appliance (K1 + K2) combined with oral myofunctional treatment (OMT) (MRC + OMT).MethodsThe study included 22 children (6 boys and 16 girls aged 9–11 years) with Class II division 1 malocclusion along with mandibular retrognathism with a 5–12 mm overjet, basic normal maxillary status, and stage 2 or 3 cervical vertebral maturation (CVM). Participants were randomly assigned into two groups, the TB group and the MRC + OMT group for 12 months. Standardized lateral cephalograms were used to assess skeletal, dental, and soft tissue changes from pre- to post-treatment. Independent t-tests were used to compare the initial and final cephalometric status and tissue changes between the groups.ResultsThe TB and MRC + OMT groups resulted in different degrees of lateral changes; however, improvements of skeletal and soft tissue indices were significantly greater in the TB group than in the MRC + OMT group.ConclusionTB was more effective than MRC + OMT in treating children aged 9–11 years with Class II division 1 malocclusion. However, further research using custom-made appliances with OMT is recommended, and further investigations are needed to confirm these findings.     

Adult Stem Cell Mobilization Enhances Intramembranous Bone Regeneration: A Pilot Study

Background  

Stem cell mobilization, which is defined as the forced egress of stem cells from the bone marrow to the peripheral blood (PB) using chemokine receptor agonists, is an emerging concept for enhancing tissue regeneration. However, the effect of stem cell mobilization by a single injection of the C-X-C chemokine receptor type 4 (CXCR4) antagonist AMD3100 on intramembranous bone regeneration is unclear.     

Cell Proliferation in Bone Marrow and Thymus Following Soft Tissue Damage

Earlier experiments by the author have shown that an increase in mitosis in bone marrow and thymus occurs after fractures and bone marrow aspiration. In this paper it is shown that soft tissue damage causes a statistically certain increase in mitosis both in bone marrow and thymus after 1 day. A possible explanation for this is liberation of a mitogenic kinin.     

Navigation-assisted Surgery for Bone and Soft Tissue Tumors With Bony Extension

Background  

The navigation system was introduced to orthopaedic surgery in the 1990s. More recently, CT-based navigation systems have been used more commonly in spine and joint replacement surgery because of their precision.     

Study of Cell Viability and Etiology of Contamination in Decalcified Bone Allograft: A Pilot Study

BackgroundBone allografts can elicit immune responses which is correlated with the presence of Human Leukocyte Antigen (HLA) and cellular DNA. It also has risk of causing occult infection arising out of contamination during its processing and storage. The presence of immunogenic materials like cells, cellular remnants and DNA in a decalcified bone allograft during different phases of processing has never been studied. Present study was conducted to explore- the cell viability using routine Hematoxylin and Eosin, presence of DNA using Feulgen staining and etiology of contamination in decalcified bone allograft during procurement, demineralization and ethanol preservation.MethodsThe harvested bones from patients undergoing hemireplacement/THR/TKR were processed to prepare decalcified bone allografts. The samples during procurement (A), HCL treatment (B) and ethanol preservation (C) were sent for histopathological analysis (number of osteocytes in the maximum density field under 40x and the cells demonstrating presence of DNA on feulgen stain) and microbiological assessment (aerobic/anaerobic/fungal cultures).ResultsHistopathological study demonstrated the presence of osteocytes and other cells like bone marrow, adipocytes, endothelial cells in the decal bone allograft. The average number of osteocytes gradually decreased from 55.47, 9.6, 0.86 in sample A, B, C, respectively. Feulgen staining confirmed the presence of DNA in osteocytes and other cells which decreased both qualitatively and quantitatively in subsequent stages of processing. Rate of contamination demonstrated at the procurement was 6.67% (Staphylococcus aureus). After treatment with HCl (demineralisation), 7.14% of non-contaminated allografts were found contaminated (Staphylococcus epidermidis). None of the remaining 13 non-contaminated allografts showed contamination after storage in ethanol. Overall 13% of the patients had positive cultures on microbiological assessment.ConclusionThe population of osteocytes in the harvested bone reduced significantly after processing with HCl and ethanol preservation. Presence of DNA, demonstrated by using Feulgen staining, was observed in bone marrow cells, adipocytes along with osteocytes which showed quantitative reduction on processing. Hence, antigenicity, conferred by cells and their DNA, reduced significantly after processing of decal bone. Contamination rate of banked decalcified allograft was 13%. Thus, culture and sensitivity tests should be carried out at each step of processing of decal bone allograft.