Quantitative Bone Single Photon Emission Computed Tomography Imaging for Uninfected Nonunion: Comparison of Hypertrophic Nonunion and Non-Hypertrophic Nonunion

Oe, Keisuke; Zeng, Feibi; Fukui, Tomoaki; Nogami, Munenobu; Murakami, Takamichi; Matsumoto, Tomoyuki; Kuroda, Ryosuke; Niikura, Takahiro

doi:10.21203/rs.3.rs-129839/v1

Cited by 3 publications

(6 citation statements)

References 12 publications

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“…[6, 7] However, the result of the Alizarin Red S staining comparing the RIA-derived cells revealed that the NHNCs were less calci ed than the BMSCs, which might explain why NHNCs do not show callus formation on X-ray ndings. [5] Based on the results of the real-time RT-PCR, we consider that this might also occur because the expression levels of OSX, BSP, and OCN are not upregulated. BMP-2 has been widely studied as an osteogenic growth factor and demonstrated to induce bone formation.…”

Section: Discussionmentioning

confidence: 99%

“…Non-hypertrophic nonunion was de ned as nonunion without radiological callus formation including oligotrophic, comminuted (torsion-wedge, dystrophic, and necrotic), defect, and atrophic types in the Weber and Cech classi cation and was con rmed by three senior orthopedic trauma surgeons. [3,5] Five patients with non-hypertrophic nonunion surgically treated in our institution were enrolled (Table 1). The patient characteristics were as follows: mean age, 36.6 (range 20-59) years; sex, three male and two female patients; fracture sites, one tibial diaphysis, one clavicle diaphyseal, and three femoral diaphysis fractures.…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…[3,4] Furthermore, we reported that the standardized uptake value on bone single-photon emission computed tomography is lower in non-hypertrophic than in hypertrophic nonunion. [5] Assessment of biological activity in nonunion tissue is essential to develop effective treatment strategies for nonunion. We previously reported that tissue in hypertrophic nonunion contains multilineage mesenchymal progenitor cells, [6] and osteogenic cells are expressed in pseudoarthrosis tissue.…”

Section: Introductionmentioning

confidence: 99%

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Human Non-hypertrophic Nonunion Tissue Contains Osteoblast Lineage Cells and E-BMP-2 Activates Osteogenic and Chondrogenic Differentiation

Yoshikawa

Fukui

et al. 2022

Preprint

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Background: Nonunions without hypertrophic callus formation has been identified based on X-ray findings, and we have defined it as non-hypertrophic nonunion. Bone morphogenetic protein-2 (BMP-2) is a well-known growth factor for bone regeneration, and Escherichia coli-derived BMP-2 (E-BMP-2) is considered a low-cost alternative to currently available products for humans. In this in vitro study, we examined the proliferation capability and osteogenic and chondrogenic differentiation potential of non-hypertrophic nonunion cells (NHNCs), and the effect of E-BMP-2 on them.Methods: We enrolled five patients with non-hypertrophic nonunion. NHNCs isolated from nonunion tissue sampled during surgery were cultured, passaged, and counted every 14 days. The surface antigen profiles of NHNCs were characterized using flow cytometry. Osteogenic differentiation capability was assessed using Alizarin Red S staining, alkaline phosphatase activity assay, and real-time reverse transcription-polymerase chain reaction (RT-PCR) after culturing in osteogenic medium. Furthermore, chondrogenic differentiation capability was assessed using Safranin-O staining and real-time RT-PCR after culturing in chondrogenic medium. To examine the effect of E-BMP-2 on the proliferation, osteogenic differentiation, and chondrogenic differentiation of NHNCs, they were cultured in each medium supplemented with 100 ng/mL E-BMP-2.Results: NHNCs were homogenous fibroblastic adherent cells and long-lived through at least 10 passages, with a slight decline. Flow cytometry revealed that the cells were consistently positive for mesenchymal stem cell-related markers CD73 and CD105, and negative for the hematopoietic markers CD14 and CD45. NHNCs were capable of differentiating into osteoblast lineage cells; however, they did not have strong calcification or sufficient chondrogenic differentiation capability. E-BMP-2 did not affect the proliferative capability of the cells but improved their osteogenic differentiation capability by increasing alkaline phosphatase activity and upregulating the gene expression of osterix, bone sialoprotein, and osteocalcin. Moreover, E-BMP-2 enhanced their chondrogenic differentiation capability by upregulating the gene expression of aggrecan and collagen type II.Conclusions: We showed for the first time that NHNCs had the capacity to differentiate into osteoblast-lineage cells, although the chondrogenic differentiation potential was poor. Local application of E-BMP-2 with preservation of nonunion tissue could be a treatment option for non-hypertrophic nonunion by promoting osteogenesis and chondrogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Patient Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human Non-hypertrophic Nonunion Tissue Contains Osteoblast Lineage Cells and E-BMP-2 Activates Osteogenic and Chondrogenic Differentiation

Yoshikawa

Fukui

et al. 2022

Preprint

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“…Recently, Bhure et al reported on the value of single-photon emission computed tomography / computed tomography (SPECT/CT) in the evaluation of necrotic bone fragments in patients with delayed bone healing or nonunion following traumatic fractures and concluded that SPECT/CT is an accurate tool in the evaluation of such patients and is superior to conventional planar BS [61]. In addition, Oe et al found that standardized uptake value (SUV) can be quantified from SPECT of nonunion sites, indicating that quantitative SPECT parameters including SUVmax, SUVpeak, and SUVmean provide a potentially useful tool for assessing the metabolic activity of nonunions [62]. Nevertheless, these studies have mainly examined the need for autologous bone grafting to allow for appropriate surgical intervention, leaving unresolved the issue of distinguishing between delayed union and nonunion.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Oe et al . found that standardized uptake value (SUV) can be quantified from SPECT of nonunion sites, indicating that quantitative SPECT parameters including SUVmax, SUVpeak, and SUVmean provide a potentially useful tool for assessing the metabolic activity of nonunions [62]. Nevertheless, these studies have mainly examined the need for autologous bone grafting to allow for appropriate surgical intervention, leaving unresolved the issue of distinguishing between delayed union and nonunion.…”

Section: Discussionmentioning

confidence: 99%

Wireless Measurements Using Electrical Impedance Spectroscopy to Monitor Fracture Healing

Fukase

Duke

Lin

et al. 2022

Preprint

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There is an unmet need for improved, clinically relevant methods to longitudinally quantify bone healing during fracture care. Here we develop a smart bone plate to wirelessly monitor healing utilizing electrical impedance spectroscopy (EIS) to provide real time data on tissue composition within the fracture callus. To validate our technology, we created a 1 mm rabbit tibial defect and fixed the bone with a standard veterinary plate modified with a custom-designed housing that included two impedance sensors capable of wireless transmission. Impedance magnitude and phase measurements were transmitted every 48-hours for up to 10-weeks. Bone healing was assessed by X-ray, uCT, and histomorphometry. Our results indicated the sensors successfully incorporated into the fracture callus and did not impede repair. Electrical impedance, resistance, and reactance increased steadily from weeks 3 to 7, corresponding to the transition from hematoma to cartilage to bone within the fracture gap, then plateaued as the bone began to consolidate. These three electrical readings significantly correlated with traditional measurements of bone healing and successfully distinguished between union and not healed fractures, with the strongest relationship found with impedance magnitude. These results suggest that our EIS smart bone plate can provide continuous and highly sensitive quantitative tissue measurements throughout the course of fracture healing to better guide personalized clinical care.

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Pseudarthrosen beim Erwachsenen – ein Update

Braun¹,

Menger²,

Reumann³

et al. 2022

Orthopädie und Unfallchirurgie up2date

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Trotz modernster therapeutischer Möglichkeiten bleibt je nach Frakturentität und initialer Versorgung unverändert in über 10% der Fälle die knöcherne Durchbauung eines Knochenbruchs aus. Wenn diese Fraktur ohne eine weitere therapeutische Maßnahme, entweder operativer oder konservativer Art, nicht zur Ausheilung kommt, liegt eine manifeste Pseudarthrose vor. Der Beitrag zeigt aktuelle diagnostische Standardabläufe und gibt eine Übersicht zu den Behandlungsoptionen der häufigsten adulten Pseudarthrosen.

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Quantitative Bone Single Photon Emission Computed Tomography Imaging for Uninfected Nonunion: Comparison of Hypertrophic Nonunion and Non-Hypertrophic Nonunion

Cited by 3 publications

References 12 publications

Human Non-hypertrophic Nonunion Tissue Contains Osteoblast Lineage Cells and E-BMP-2 Activates Osteogenic and Chondrogenic Differentiation

Human Non-hypertrophic Nonunion Tissue Contains Osteoblast Lineage Cells and E-BMP-2 Activates Osteogenic and Chondrogenic Differentiation

Wireless Measurements Using Electrical Impedance Spectroscopy to Monitor Fracture Healing

Pseudarthrosen beim Erwachsenen – ein Update

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