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Chronic kidney disease (CKD) mineral bone disorder has long-term effects on skeletal integrity and growth. Abnormalities in serum markers of mineral metabolism are evident early in pediatric CKD. Bone deformities, poor linear growth, and high rates of fractures are common in children with CKD. Newer imaging modalities such as high-resolution peripheral quantitative computed tomography shows promise in assessing bone mineral density more comprehensively and predicting incident fractures. A lack of large-scale studies that provide a comprehensive assessment of bone histology and correlations with serum biomarkers has contributed to the absence of evidence-based guidelines and suboptimal management of CKD mineral bone disorder in children with CKD. [ABSTRACT FROM AUTHOR]

Massive bone allografts enable the reconstruction of critical bone defects in numerous conditions (e.g. tumoral, infection or trauma). Unfortunately, their biological integration remains insufficient and the reconstruction may suffer from several postoperative complications. Perfusion-decellularization emerges as a tissue engineering potential solution to enhance osseointegration. Therefore, an intrinsic vascular study of this novel tissue engineering tool becomes essential to understand its efficacy and applicability. 32 porcine long bones (humeri and femurs) were used to assess the quality of their vascular network prior and after undergoing a perfusion-decellularization protocol. 12 paired bones were used to assess the vascular matrix prior (N = 6) and after our protocol (N = 6) by immunohistochemistry. Collagen IV, Von Willebrand factor and CD31 were targeted then quantified. The medullary macroscopic vascular network was evaluated with 12 bones: 6 were decellularized and the other 6 were, as control, not treated. All 12 underwent a contrast-agent injection through the nutrient artery prior an angio CT-scan acquisition. The images were processed and the length of medullary vessels filled with contrast agent were measured on angiographic cT images obtained in control and decellularized bones by 4 independent observers to evaluate the vascular network preservation. The microscopic cortical vascular network was evaluated on 8 bones: 4 control and 4 decellularized. After injection of gelatinous fluorochrome mixture (calcein green), non-decalcified fluoroscopic microscopy was performed in order to assess the perfusion quality of cortical vascular lacunae. The continuity of the microscopic vascular network was assessed with Collagen IV immunohistochemistry (p -value = 0.805) while the decellularization quality was observed through CD31 and Von Willebrand factor immunohistochemistry (p -values <0.001). The macroscopic vascular network was severely impaired after perfusion-decellularization; nutrient arteries were still patent but the amount of medullary vascular channels measured was significantly higher in the control group compared to the decellularized group (p -value <0.001). On average, the observers show good agreement on these results, except in the decellularized group where more inter-observer discrepancies were observed. The microscopic vascular network was observed with green fluoroscopic signal in almost every canals and lacunae of the bone cortices, in three different bone locations (proximal metaphysis, diaphysis and distal metaphysis). Despite the aggressiveness of the decellularization protocol on medullary vessels, total porcine long bones decellularized by perfusion retain an acellular cortical microvascular network. By injection through the intact nutrient arteries, this latter vascular network can still be used as a total bone infusion access for bone tissue engineering in order to enhance massive bone allografts prior implantation. [Display omitted] • This study shows how a total bone can be used as a pediculed whole organ for tissue engineering purpose. • This study brings insights in the understanding of total bone decellularization by perfusion. • This study is a step forward a new generation of massive bone allografts. • This study reinforces the importance and complexity of bone vascularization. [ABSTRACT FROM AUTHOR]

• Current techniques for assessing vertebral fracture risk are limited in accuracy. • DTS-DVC allows for clinical assessment of vertebral bone deformation. • Displacement spatial distributions qualitatively agreed between DTS-DVC and μCT-DVC. • DTS-DVC derived displacement and stiffness were strongly correlated with μCT values. • Results support use of DTS-DVC for clinical evaluation of vertebral bone quality. Digital tomosynthesis (DTS) is a clinically available modality that allows imaging of a patient's spine in supine and standing positions. The purpose of this study was to establish the extent to which vertebral displacement and stiffness derived from DTS-based digital volume correlation (DTS-DVC) are correlated with those from a reference method, i.e., microcomputed tomography-based DVC (μCT-DVC). T11 vertebral bodies from 11 cadaveric donors were DTS imaged twice in a nonloaded state and once under a fixed load level approximating upper body weight. The same vertebrae were µCT imaged in nonloaded and loaded states (40 μm voxel size). Vertebral displacements were calculated at each voxel using DVC with pairs of nonloaded and loaded images, from which endplate-to-endplate axial displacement (D DVC) and vertebral stiffness (S DVC) were calculated. Both D DVC and S DVC demonstrated strong positive correlations between DTS-DVC and μCT-DVC, with correlations being stronger when vertebral displacement was calculated using the median (R2=0.80; p <0.0002 and R2=0.93; p <0.0001, respectively) rather than average displacement (R2=0.63; p <0.004 and R2=0.69; p <0.002, respectively). In conclusion, the demonstrated relationship of DTS-DVC with the μCT standard supports further development of a biomechanics-based clinical assessment of vertebral bone quality using the DTS-DVC technique. [ABSTRACT FROM AUTHOR]

Bone stress injuries (BSI) are common among distance runners and research investigations examining risk factors for BSI among men are limited. Therefore, investigations are needed to determine if men with a history of BSI have skeletal properties that may heighten BSI incidence.Objectives: To analyze differences in bone density, bone geometry, and estimates of bone strength in male runners with and without a BSI history.Design: Cross-sectional.Methods: We recruited 36 male distance runners ages 18-41 for this study. We used peripheral quantitative computed tomography (pQCT) to assess volumetric bone mineral density (vBMD, mg/mm3), bone geometry (total and cortical bone area, mm2), tibia robustness (total area/tibia length, mm) and estimates of bone strength (section modulus and polar strength-strain index, mm3) at 5 tibial sites.Results: After adjusting for age, the BSI group had more slender tibias (9%), lower stress strain indices (-16%), lower section moduli (-17%) and smaller total cross-sectional (-11%) and cortical areas (-12%) at the 66% site of the tibia compared with controls (P < 0.05 for all). Similar differences were found at all other measurement sites. After adjusting for body size, differences in bone outcomes remained significant at the 66% site.Conclusions: These results indicate that men with a history of BSI have lower estimated bending strength compared to controls because of narrower tibias. However, differences are largely attenuated in the distal ½ of the tibia after adjusting for body size. Thus, smaller tibia size, particularly at the mid-diaphysis, may be an important indicator for BSI incidence. [ABSTRACT FROM AUTHOR]

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a non-invasive method of measuring volumetric bone mineral density (vBMD) and microarchitecture at the distal radius and tibia. With increasing use of this technology, it is crucial to understand the potential impact of overlying soft tissue on the accuracy of HR-pQCT measures. Thus, we examined the effects of a simulated increase in adiposity (via 6- and 12-mm thick layers of overlying circumferential fat) on HR-pQCT measures of a hydroxyapatite (HA) phantom and in women (n = 20, aged 18–75 years). In the phantom, increasing the amount of overlying fat tissue led to a corresponding decrease in the mean measured density for each HA rod. In women, fat-layering led to a decrease in total vBMD (−2.9 to −3.7%, p < 0.001), cortical vBMD (−1.4% to −5.5%, p < 0.001), and estimated failure load (−1.4 to −5.7%, p = 0.002) at the radius, with similar changes in the tibia. Trabecular microarchitectural measurements were also impacted by simulated adiposity, with fat-layering leading to decreased trabecular thickness and separation and increased trabecular number at the radius (Δ's = 5 to 12%) with more pronounced differences at the tibia (Δ's = 14 to 40%). At the tibia, fat-layering also led to decreased cortical thickness and increased cortical porosity. Altogether, these results demonstrate that overlying adipose tissue can lead to artifacts in bone measurements by HR-pQCT, resulting in an underestimation of vBMD and generally, an overestimation of bone microarchitecture impairment. Therefore, soft tissue artifact should be considered when interpreting HR-pQCT results, particularly in those with high BMI and/or marked changes in adiposity. • High-resolution peripheral QCT (HR-pQCT) is used increasingly. • Overlying adipose tissue can lead to artifacts in bone measurements by HR-pQCT. • Volumetric bone mineral density is underestimated with increased adipose tissue. • Bone microarchitecture impairment is overestimated with increased adipose tissue. • Soft tissue artifact should be considered when interpreting HR-pQCT results. [ABSTRACT FROM AUTHOR]

Background The aim of this study is to propose a new method to quantify radioactivity with PET/CT imaging in mandibular extension in head and neck squamous cell carcinoma (HNSCC), using innovative software, and to compare results with microscopic surgical specimens. Patients and methods This prospective study enrolled 15 patients who underwent 18 F-NaF and 18 F-FDG PET/CT. We compared the delineations of bone invasions obtained with 18 F-NaF PET/CT and 18 F-FDG PET/CT with the results of histopathological analysis of mandibular resections (from right and left bone borders). A method for visualization and quantification of PET images was developed. Results For all patients, a significant difference ( p = 0.032 for right limits and p = 0.011 for left limits) was observed between 18 F-FDG PET/CT imaging and histopathology results, and no significant difference ( p = 0.88 for right limits and p = 0.55 for left limits) was observed between 18 F-NaF PET/CT imaging and histopathology results. The right limits were less than 10 mm in 93% of patients, and the left limits were less than 10 mm in 86% of patients. Conclusions The dedicated software enabled the objective delineation of radioactivity within the bone. We can confirm that 18 F-NaF is a precise and specific bone marker for the assessment of intraosseous mandibular extensions of head and neck cancers. Clinical question/level of evidence Therapeutic, III. [ABSTRACT FROM AUTHOR]

Ultrasound (US) imaging of an infant's hip joint is widely used for early detection of developmental dysplasia of the hip. In current US-based diagnosis of developmental dysplasia of the hip, trained clinicians acquire US images and, if they judge them to be adequate (i.e., to contain relevant hip joint structures), analyze them manually to extract clinically useful dysplasia metrics. However, both the scan adequacy classification and dysplasia metrics extraction steps exhibit significant variability within and between both clinicians and institutions, which can result in significant over- and undertreatment rates. To reduce the subjectivity resulting from this variability, we propose a computational image analysis technique that automatically identifies adequate images and subsequently extracts dysplasia metrics from these 2-D US images. Our automatic method uses local phase symmetry-based image measures to robustly identify intensity-invariant geometric features of bone/cartilage boundaries from the US images. Using the extracted geometric features, we trained a random forest classifier to classify images as adequate or inadequate, and in the adequate images we used a subset of the geometric features to calculate key dysplasia metrics. We validated our method on a data set of 693 US scans collected from 35 infants. Our approach produces excellent agreement with clinician adequacy classifications (area under the receiver operating characteristic curve = 0.985) and in reducing variability in the measured developmental dysplasia of the hip metrics (p < 0.05). The automatically computed dysplasia metrics appear to be slightly biased toward higher Graf categories than the manually estimated metrics, which could potentially reduce missed early diagnoses. [ABSTRACT FROM AUTHOR]

Deposition of calcium oxalate crystals in the kidney and bone is a hallmark of systemic oxalosis. Since the bone compartment can store massive amounts of oxalate, patients present with recurrent low-trauma fractures, bone deformations, severe bone pains and specific oxalate osteopathy on plain X-ray. Bone biopsy from the iliac crest displays specific features such as oxalate crystals surrounded by a granulomatous reaction due to an invasion of bone surface by macrophages. We present data obtained in 10 samples from 8 patients with oxalosis (16–68 years) who underwent iliac crest bone biopsy and bone quality analysis using modern methods (microradiography, microindentation, Fourier Transform InfraRed Microspectroscopy, transmission electron microscopy) in addition to histomorphometry. Disseminated calcium oxalate deposits (whewellite) were found in the bone marrow space (with a granulomatous reaction) but not in the bone matrix. Calcium oxalate deposits were totally surrounded by macrophages and multinucleated giant cells, and a phagocytosis activity was sometimes observed. Very few calcium oxalate crystals were directly in close contact with the mineral substance of the bone. Bone mineralization was not modified by the presence of calcium oxalate even in close vicinity. Bone quality analysis also revealed a harder bone than normal, perhaps in relationship with decreased carbonate content in the mineral. This increase in bone hardness could explain a more “brittle” bone. In patients with oxalosis, the formation and growth of calcium oxalate crystals in the bone appeared independent of apatite. The mechanisms leading to nucleation and growth of oxalate deposits are still unclear and deserve further studies. [ABSTRACT FROM AUTHOR]

Two bisphosphonate isocyanide derivatives (CNALN and CNPAM) could be easily synthesized and the corresponding [99mTc][Tc(I)]+ labeled complexes were successfully prepared. The biodistribution and single photon emission computed tomography (SPECT) imaging studies in mice revealed [99mTc]Tc-CNALN had an obvious accumulation in bone, suggesting it would be a promising bone-seeking agent. [Display omitted] In order to develop 99mTc-labeled complexes with bisphosphonate isocyanide as novel bone imaging agents, two bisphosphonate isocyanide derivatives (CNALN and CNPAM) were synthesized and radiolabeling was performed for preparing the corresponding [99mTc]Tc(I) complexes. [99mTc]Tc-CNALN and [99mTc]Tc-CNPAM were obtained with high radiochemical purity and showed good in vitro stability. Both of them were hydrophilic and had high affinity to hydroxyapatite. The biodistribution studies in mice revealed [99mTc]Tc-CNALN showed higher bone/background ratios at 60 min post-injection. In single photon emission computed tomography (SPECT) imaging study, [99mTc]Tc-CNALN had an obvious accumulation in bone, suggesting it would be a promising bone-seeking agent. [ABSTRACT FROM AUTHOR]

The vertebral endplate and cortical shell play an important structural role and contribute to the overall strength of the vertebral body, are at highest risk of initial failure, and are involved in degenerative disease of the spine. The ability to accurately measure the thickness of these structures is therefore important, even if difficult due to relatively low resolution clinical imaging. We posit that digital tomosynthesis (DTS) may be a suitable imaging modality for measurement of endplate and cortical shell thickness owing to the ability to reconstruct multiplanar images with good spatial resolution at low radiation dose. In this study, for 25 cadaveric L1 vertebrae, average and standard deviation of endplate and cortical shell thickness were measured using images from DTS and microcomputed tomography (μCT). For endplate thickness measurements, significant correlations between DTS and μCT were found for all variables when comparing thicknesses measured in both the overall endplate volume (R2 = 0.25–0.54) and when measurements were limited to a central range of coronal or sagittal slices (R2 = 0.24–0.62). When compared to reference values from the overall shell volume, DTS thickness measurements were generally nonsignificant. However, when measurement of cortical shell thickness was limited to a range of central slices, DTS outcomes were significantly correlated with reference values for both sagittal and coronal central regions (R2 = 0.21–0.49). DTS may therefore offer a means for measurement of endplate thickness and, within a limited sagittal or coronal measurement volume, for measurement of cortical shell thickness. • Vertebral endplate and shell thickness were measured from tomosynthesis (DTS) and μCT. • DTS derived thickness was 9.4% to 21.7% less than reference values from μCT volume. • The differences were 0.71% to 16% when DTS and μCT volumes were matched. • Moderate correlations were found (R2 to 0.62 for endplate, 0.49 for shell outcomes). • DTS offers a means for measuring endplate, and shell within central analysis regions. [ABSTRACT FROM AUTHOR]

Abstract: Two novel zoledronic acid (ZL) derivatives, 1-hydroxy-4-(1H-imidazol-1-yl)butane-1,1-diyldiphosphonic acid (IBDP) and 1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (IPeDP), were prepared and labeled with the radionuclide technetium-99m in a high labeling yield. In vitro stabilities of these radiolabeled complexes were measured by the radio-HPLC analysis as a function of time, which showed excellent stability with the radiochemical purity of over 95% at 6h post preparation. Their in vivo biological performances were evaluated and compared with those of 99mTc-ZL and 99mTc-MDP (methylenediphosphonic acid). The biodistribution in mice and scintigraphic images of the rabbit showed that the tracer agent 99mTc-IPeDP had highly selective uptake in the skeletal system and rapid clearance from the blood and soft tissues and an excellent scintigraphic image can be obtained in a shorter time post injection with clear visualization of the skeleton and low soft tissue activity. These preclinical studies suggest that 99mTc-IPeDP would be a novel superior bone scintigraphic agent. [Copyright &y& Elsevier]

Abstract: Enhanced imaging of early-stage bone abnormalities, such as primary tumors or metastases is highly required as the widely-used bone scan frequently lacks the desired sensitivity. Near IR (NIR) fluorescence imaging affords high contrast and enhanced sensitivity, as body tissue expresses minimal autofluorescence at NIR range (600–1200 nm). Indocyanine green (ICG), a biocompatible NIR dye, is widely used in the imaging of various organs, such as liver, heart and blood circulation. We report the preparation and in-vivo testing of a bone-targeting ICG derivative, in comparison to the parent molecule(s). Since ICG itself is chemically unreactive, and could not form conjugates, we prepared two novel ICG conjugatable derivatives. The overall ICG structure was maintained while only a replacement of one or two sulfonate groups with carboxylic acids resulted in new linkers for covalent binding to biomolecules. These derivatives were evaluated for their fluorescence and biodistribution in comparison to ICG and were found to be comparable. One of the novel ICG-derivatives was conjugated to a bone-targeting moiety and this new compound was found to bind to growing regions of the skeleton, and emit fluorescence for as long as two weeks in young mice. [Copyright &y& Elsevier]

Abstract: Advanced bone imaging techniques provide structural information, beyond bone mineral density (BMD), and growing evidence indicates that BMD only partially explains bone strength and fracture resistance. Assessing glucocorticoid-induced osteoporosis (GIO) is important, especially the documentation of glucocorticoid (GC) impact on trabecular and cortical bone and on macro and microstructural features. Advanced methods for assessing macrostructure of bone include volumetric quantitative computed tomography (vQCT), high-resolution computed tomography (hrCT), and high-resolution magnetic resonance imaging (hrMRI). The methods for assessing bone microstructure include micro computed tomography (μCT) and micro magnetic resonance imaging (μMRI). Many advanced imaging techniques have been used in vitro and in vivo to examine structural effects of GIO in animals and in humans, and these applications are explored in this review. In human in vitro studies, investigators have used standard bone histomorphometry and μCT to compare trabecular microarchitecture and bone remodeling in postmenopausal women and in males with GIO, and have found that high-dose GC produces dramatic bone loss, accompanied by major reduction in trabecular connectivity and increases in trabecular perforations. In animal studies, investigators have used standard histomorphometry along with pQCT, vQCT, hrMRI or μCT to examine GIO in a variety of animal models including rats, minipigs and sheep. They generally have found excellent relationships between treatment-induced structural changes assessed by these advanced imaging techniques and changes in BMD and biomechanical properties. They also have examined various therapeutic interventions in animals and monitored their efficacy using quantitative imaging methods. In human in vivo studies, investigators have serially examined postmenopausal women and males with GIO in order to assess the extent of skeletal deterioration and to determine the best advanced measures of BMD and structure, with which to monitor disease activity and therapeutic response, and to predict fracture risk. They generally have found that bone density and structural measures obtained by pQCT, vQCT and hrMRI contributed substantially to understanding the skeletal effects of glucocorticoids and to predicting the risk of fracture in human GIO. These animal and human applications, illustrating advanced imaging in GIO, are still in early stages of development. However, as discussed in this review, the novelty and power of the imaging approaches are compelling, and their utility is promising. [Copyright &y& Elsevier]

Abstract: We examined the use of high-resolution peripheral quantitative computed tomography (HR-pQCT [XtremeCT; Scanco Medical, Switzerland]) to assess bone microstructure at the distal radius in growing children and adolescents. We examined forearm radiographs from 37 children (age 8–14yr) to locate the position of the ulnar and radial growth plates. We used HR-pQCT to assess bone microstructure in a region of interest (ROI) at the distal radius that excluded the growth plate (as determined from the radiographs) in all children (n=328; 9–21 yr old). From radiographs, we determined that a ROI in the distal radius at 7% of bone length excluded the radial growth plate in 100% of participants. We present bone microstructure data at the distal radius in children and adolescents. From the HR-pQCT scans, we observed active growth plates in 80 males (aged 9.5–20.7yr) and 92 females (aged 9.5–20.2yr). The ulnar plate was visible in 9 male and 17 female participants (aged 11.2±1.9yr). The HR-pQCT scan required 3min with a relatively low radiation dose (<3μSv). Images from the radial ROI were free of artifacts and outlined cortical and trabecular bone microstructure. There is currently no standard method for these measures; therefore, these findings provide insight for investigators using HR-pQCT for studies of growing children. [ABSTRACT FROM AUTHOR]

Purpose: 18F-NaF PET is valuable for detecting bone metabolism through osteoblastic activity in the assessment of bone disease. Hawkins, Patlak, and standardised uptake value (SUV) are the most common quantitative measurements used to evaluate bone metabolism. This systematic review evaluates the correlation between quantitative positron emission tomography (PET) methods and to compare their precision.Methods: A systematic search in Medline, PubMed, SCOPUS, and Web of Science was undertaken to find relevant papers published from 2000. All studies with human adults undergoing 18F-NaF PET, PET/CT, or PET/MRI were included except for subjects diagnosed with non-diffuse metabolic bone disease or malignancy. Quality Assessment Tool for Studies of Diverse Designs (QATSDD) was used to assess risk of bias. A qualitative review and meta-analysis using Hedges random-effect model was used producing summary size effects of the correlation between methods in healthy and unhealthy bone sites and assessing study heterogeneity.Results: 228 healthy and unhealthy participants were included across 12 studies resulted from the systematic search. One-third of studies had a moderate quality percentage while the rest had relatively high quality. The pooled correlation coefficient in meta-analysis showed a high correlation of more than 0.88 (0.71-1.05. 95 %CI) between SUV and Hawkins and more than 0.96 (0.88-1.03. 95 %CI) between Patlak and Hawkins within all subgroups, suggesting all methods yield similar results in healthy and unhealthy bone sites. SUV has the lowest precision error followed by Patlak while Hawkins method showed the highest precision error.Conclusion: Patlak is the best within research and SUV is better within clinical practice. [ABSTRACT FROM AUTHOR]

Susceptibility to fracture is increased across the spectrum of chronic kidney disease (CKD). Moreover, fracture in patients with end-stage kidney disease (ESKD) results in significant excess mortality. The incidence and prevalence of CKD and ESKD are predicted to increase markedly over the coming decades in conjunction with the aging of the population. Given the high prevalence of both osteoporosis and CKD in older adults, it is of the utmost public health relevance to be able to assess fracture risk in this population. Dual-energy X-ray absorptiometry (DXA), which provides an areal measurement of bone mineral density (aBMD), is the clinical standard to predict fracture in individuals with postmenopausal or age-related osteoporosis. Unfortunately, DXA does not discriminate fracture status in patients with ESKD. This may be, in part, because excess parathyroid hormone (PTH) secretion may accompany declining kidney function. Chronic exposure to high PTH levels preferentially causes cortical bone loss, which may be partially offset by periosteal expansion. DXA can neither reliably detect changes in bone volume nor distinguish between trabecular and cortical bone. In addition, DXA measurements may be low, normal, or high in each of the major forms of renal osteodystrophy (ROD). Moreover, postmenopausal or age-related osteoporosis may also affect patients with CKD and ESKD. Currently, transiliac crest bone biopsy is the gold standard to diagnose ROD and osteoporosis in patients with significant kidney dysfunction. However, bone biopsy is an invasive procedure that requires time-consuming analyses. Therefore, there is great interest in developing non-invasive high-resolution imaging techniques that can improve fracture risk prediction for patients with CKD. In this paper, we review studies of fracture risk in the setting of ESKD and CKD, the pathophysiology of increased fracture risk in patients with kidney dysfunction, the utility of various imaging modalities in predicting fracture across the spectrum of CKD, and studies evaluating the use of bisphosphonates in patients with CKD.Kidney International (2008) 74, 721–731; doi:10.1038/ki.2008.264; published online 18 June 2008 [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The present study aimed to develop convenient preparation and quality control protocols for [68Ga]-EDTMP, a potential radiotracer for skeletal PET imaging. Furthermore, bone binding characteristics with special focus on the influence of carrier addition were evaluated. Methods: No-carrier-added (nca), carrier-added and novel cross-complexed [68Ga]-EDTMP formulations were prepared using [68Ga]-gallium chloride and a commercial EDTMP kit. Respective bone binding characteristics were determined on the basis of an established in-vitro method using hydroxyapatite and human bone powders as binding matrices. Results: Pre-vivo evaluation of nca [68Ga]-EDTMP yielded irreversible binding on the mineral bone phase characterised by fast binding kinetics. Generally, nca [68Ga]-EDTMP showed low uptake values comparable to nca [99mTc]-EDTMP. Interestingly, the bone binding affinity of [68Ga]-EDTMP could be increased by the addition of carriers, presumably by changing the complex structure. Conclusions: This fast and reliable preparation protocol could enable small PET facilities without onsite cyclotron to perform PET bone scans. A comparison of all cross-complexed [68Ga]-EDTMP preparations further strengthens the recently presented “foreign carrier theory”, which highlights carrier addition as a factor strongly affecting bone uptake of radiolabelled polyphosphonates. The clinical applicability of [68Ga]-EDTMP – particularly with respect to lesion specificity and sensitivity – should be clarified in forthcoming in-vivo studies. [Copyright &y& Elsevier]

Abstract: An accurate analysis and quantification of microdamage is critical to understand how microdamage affects the mechanics and biology of bone fragility. In this study we demonstrate the development and validation of a novel in vitro micro-computed tomography (microCT) method that employs lead–uranyl acetate as a radio-opaque contrast agent for automated quantification of microdamage in trabecular bone. Human trabecular bone cores were extracted from the femoral neck, scanned via microCT, loaded in unconfined compression to a range of apparent strains (0.5% to 2.25%), stained in lead–uranyl acetate, and subsequently re-scanned via microCT. An investigation of the regions containing microdamage using the backscatter mode of a scanning electron microscope (BSEM) showed that the lead–uranyl sulfide complex was an effective contrast agent for microdamage in bone. Damaged volume fraction (DV/BV), as determined by microCT, increased exponentially with respect to applied strains and proportionately to mechanically determined modulus reduction (p <0.001). Furthermore, the formation of microdamage was observed to occur before any apparent stiffness loss, suggesting that the localized tissue yielding occurs prior to the structural yielding of trabecular bone. This non-invasive in vitro technique for the detection of microdamage using microCT may serve as a valuable complement to existing morphometric analyses of bone. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to investigate the application of three-dimensional rotational X-ray imaging (3D-RX) for the depiction of the trabecular bone structure. In seven specimens of human vertebrae with varying bone density, 3D images were reconstructed from projection data acquired during a single-axis rotation of the C-arm gantry over an angular range of 220°. All images were reconstructed at an isotropic spatial resolution of 1503 μm3. The resulting images were compared to μ-CT images reconstructed at the same spatial resolution. The reconstructed images show that trabecular bone structures below 100 μm and structural variations can be clearly resolved in cases the contrast between the structure and the surrounding tissue is sufficiently high. [Copyright &y& Elsevier]

The aim of this research is to develop polymeric micelle system as a targetable bone imaging carriers without nonspecific phagocytosis which is made of polyethylene oxide (PEO) and polycaprolactone (PCL). Diamino-PEO, which has two amino groups in its structure, was used to conjugate both PCL and ligand for specific radioisotope. PCL was conjugated to one amino group of diamino-PEO by using diaminohexyl cyclocarbodiimide (DCC), coupling agent. Hydroxyphenylpropionic acid (HPP), diethylenetriamine pentaacetic acid (DTPA) and mercaptoacetyl glycine glycidyl glycine (MAG3), as ligands for specific radioisotopes, were coupled to the rest of amino group of diamino-PEO by the same method as described. Formation of ligand-conjugated block copolymers, critical micelle concentration (CMC) of the copolymers, hydrodynamic radii, and morphology of the micelles were investigated. Besides, 125I-labelling efficiency and biodistribution of the micelles were examined. PEO–PCL block copolymer micelles demonstrated CMC of 25 mg/l and size of 60 nm, which may be adequate for blood vessel and bone imaging. 125I-labelling efficiency was above 90% and was more stable at human serum for 24 h. 125I-labelled polymeric micelles showed higher blood maintenance and bone uptake when compared to stannous colloid, used as a control. A noticeable decrease in liver or spleen uptake could be achieved by the micelles. Therefore, radioisotope carrying PEO–PCL micelle system was suggested as a useful tool for effective diagnostic bone targeting and imaging. [Copyright &y& Elsevier]

α,α-Bisphosphonates (BPs) are well established in the treatment of bone diseases such as osteoporosis and Paget's disease. Their successful application originates from their high affinity to hydroxyapatite. While the initially appreciated features of BPs are already beneficial to many patients, recent developments have further expanded their pleiotropic applications. This review describes the background of the interactions of BPs with bone cells that form the basis of the classical treatment. A better understanding of the mechanism behind their interactions allows for the parallel application of BPs against bone cancer and metastases followed by palliative pain relief. Targeted therapy with bone-seeking BPs coupled with a diagnostic agent in one particle resulted in theranostics which is also described here. For example, in such a system, BP moieties are bound to contrast agents used in magnetic resonance imaging or radionuclides used in positron emission tomography. In addition, another example of the pleiotropic function of BPs which involves targeting the imaging agents to bone tissues accompanied by pain reduction is presented in this work. Image 1 • Bisphosphonates express a high affinity to hydroxyapatite and thus to bones. • Classically Paget's disease and osteoporosis are treated with bisphosphonates. • Pleiotropic effects were found for cancer and metastases treatment. • Palliative antipain and contrast agent applications are under investigation. [ABSTRACT FROM AUTHOR]