Bone Microstructure Parameters Research Articles

Associations between cortical bone-to-implant contact and microstructure derived from CBCT and implant primary stability.

To evaluate the associations between the cortical bone-to-implant contact (CBIC), bone microstructure derived from cone-beam computed tomography (CBCT), and the primary stability of the implant. Twenty-two patients with 65 implants were enrolled in this study. The peak insertion torque values (ITVs) were measured during implant insertion, and the implant stability quotient (ISQ) values were measured immediately after implant placement and 3months after surgery. The profiles of the peri-implant bone structure were outlined using the volumetric reconstruction of the CBCTs and superimposition of the virtual models, and the features of CBIC and bone microstructure parameters were measured. The linear mixed effects model and generalized estimating equation were used to explore the predictors for implant primary stability. The average ITV, baseline, and secondary ISQ values were 31.44 ± 6.54 N·cm, 73.34 ± 7.39, and 80.32 ± 4.58, respectively. Statistically significant correlations were found between ITV and surface area of CBIC (r= .340, p= .006), bone volume fraction (r= .294, p= .017), and bone surface fraction (r= -.278, p= .039). Implants with buccolingual CBIC had a higher ITV than implants without CBIC (p= .016). None of the parameters were associated with baseline and secondary ISQ values in generalized estimating equation analysis (all p> .05). Within the limitations of the study, preoperative CBCT measurements might enable the prediction of ITV and therefore of implant primary stability values.

Open-source pipeline for automatic segmentation and microstructural analysis of murine knee subchondral bone.

A segmented dataset of μCT scans from 62 knees (healthy and arthritic) from 10-week male C57BL/6 mice was used to train a U-Net type architecture to automate segmentation of the subchondral trabecular bone. These segmentations were used in tandem with the original scans as input for microstructural analysis along with thresholded trabecular bone. Manually and U-Net segmented ROIs were fed into two available pipelines for microstructural analysis: the ITKBoneMorphometry library and CTan (SKYSCAN). Outcome parameters were compared between pipelines, including: bone volume (BV), total volume (TV), BV/TV, trabecular number (TbN), trabecular thickness (TbTh), trabecular separation (TbSp), and bone surface density (BSBV). There was good agreement for all bone measures comparing the manual and U-Net pipelines utilizing ITK (R = 0.88-0.98) and CTAn (R = 0.91-0.98). ITK and CTAn showed good agreement for BV, TV, BV/TV, TbTh and BSBV (R = 0.9-0.98). However, limited agreement was seen between TbN (R = 0.73) and TbSb (R = 0.59) due to methodological differences in how spacing is evaluated. Microstructural parameters generated from manual and automatic segmentations showed high correlation across all measures. Using the CTAn pipeline yielded strong R2 values (0.83-0.96) and very strong agreement based on ICC (0.90-0.98). The ITK pipeline yielded similarly high R2 values (0.91-0.96, except for TbN (0.77)), and ICC values (0.88-0.98). The automated segmentations yield lower average values for BV, TV and BV/TV (ranging from 14 % to 6.3 %), but differences were not found to be influenced by the mean ROI values. This integrated pipeline seamlessly automated both segmentation and quantification of the proximal tibia subchondral bone microstructure. This automated pipeline allows the analysis of large volumes of data, and its open-source nature may enable the standardization of microstructural analysis of trabecular bone across different research groups.

Effect of Desmodium renifolium on ovariectomized rat model of osteoporosis via BMP-2/Smads signaling pathway

This study aimed to investigate the effect of Desmodium renifolium(Linn.) Schindl on ovariectomized rat model of osteoporosis and explore the underlying mechanism. Rats were randomized into a sham group, a model group, a Xianlin Gubao group, and low-, medium-, and high-dose D. renifolium groups. Bilateral oophorectomy was performed in other groups except sham group(removal of bilateral peri-ovarian adipose tissue). The sham group and model group were administrated with equal volume of 0.5% CMC-Na, Xianlin Gubao group with Xianlin Gubao, and D. renifolium groups with different concentrations of alcoholic extract of D. renifolium once a day for 14 weeks. The body weight of rats were recorded during the experiment. The levels of estradiol(E_2), 1,25-dihydroxyvitamin D_3 [1,25(OH)_2D_3], calcium(Ca), and phosphorus(P) in serum were determined after the administration. The femur microstructure was analyzed via micro-CT. RT-PCR and Western blot were employed to respectively determine the mRNA and protein levels of bone morphogenetic protein 2(BMP-2), Runt-related transcription factor 2(Runx2), and osterix(OSX) in the tibia of rats. The results indicated that D. renifolium significantly inhibited the weight growth, improved the uterus appearance, elevated the levels of E_2, Ca, P, and 1,25(OH)_2D_3 in serum, increased the number and reduced the fracture of bone trabeculae, ameliorated the bone microstructure parameters, and up-regulated the mRNA and protein levels of BMP-2, Runx2, and OSX. All the results demonstrated that D. renifolium had significant protective effect on the ovariectomized rat model of osteoporosis by regulating the BMP-2/Smads signaling pathway.

Assessment of Bone Microstructure by Micro CT in C57BL/6J Mice for Sex-Specific Differentiation

It remains uncertain which skeletal sites and parameters should be analyzed in rodent studies evaluating bone health and disease. In this cross-sectional mouse study using micro-computed tomography (µCT), we explored: (1) which microstructural parameters can be used to discriminate female from male bones and (2) whether it is meaningful to evaluate more than one bone site. Microstructural parameters of the trabecular and/or cortical compartments of the femur, tibia, thoracic and lumbar vertebral bodies, and skull were evaluated by µCT in 10 female and 10 male six-month-old C57BL/6J mice. The trabecular number (TbN) was significantly higher, while the trabecular separation (TbSp) was significantly lower in male compared to female mice at all skeletal sites assessed. Overall, bone volume/tissue volume (BV/TV) was also significantly higher in male vs. female mice (except for the thoracic spine, which did not differ by sex). Most parameters of the cortical bone microstructure did not differ between male and female mice. BV/TV, TbN, and TbSp at the femur, and TbN and TbSp at the tibia and lumbar spine could fully (100%) discriminate female from male bones. Cortical thickness (CtTh) at the femur was the best parameter to detect sex differences in the cortical compartment (AUC = 0.914). In 6-month-old C57BL/6J mice, BV/TV, TbN, and TbSp can be used to distinguish male from female bones. Whenever it is not possible to assess multiple bone sites, we propose to evaluate the bone microstructure of the femur for detecting potential sex differences.

Exploring the relationship of brown adipose tissue to bone microarchitecture using 7T MRI and micro-CT.

Brown adipose tissue (BAT) is involved both in energy production and bone metabolism. The purpose of this study was to analyze the relationship between BAT and microarchitecture at cancellous and cortical bone using Kunming mice and the methods of 7T magnetic resonance imaging (MRI) combined with micro-CT. Twenty-four female Kunming mice were examined by 7T MRI and measured T2* relaxation time on the deep and superficial interscapular BAT (iBAT) and subcutaneous white adipose tissue (sWAT). Cancellous bone microarchitecture of the distal femur and cortical bone of the middle femur were examined by micro-CT. A paired t-test was used to analyze the differences in T2* values between iBAT and sWAT. The correlation between BAT T2* values and bone microstructure parameters were analyzed using Pearson's correlation. T2* values of the deep and superficial iBAT (6.36±3.31 ms and 6.23±2.61 ms) were significantly shorter than those of sWAT (16.30±3.05 ms, t(deep) iBAT=-10.816), t(superficial) iBAT =-12.276, p<0.01). Deep iBAT T2* values were significantly and negatively correlated with bone volume, cancellous thickness, and bone thickness (Th) and trabecular thickness (Tb.Th) of the cancellous bone of femur. Deep iBAT T2* values were significantly and positively correlated with the structural model index of cancellous bone of femur. Deep iBAT T2* values were significantly and negatively correlated with bone mineral density of the cortical bone of femur. MRI can distinguish the two adipose tissues from each other. T2* values of BAT were lower than WAT on MRI. BAT related bone remodeling was more correlated with the microstructure of cancellous bone than that of cortical bone.

Quantifications of Mandibular Trabecular Bone Microstructure Using Cone Beam Computed Tomography for Age Estimation: A Preliminary Study.

Simple SummaryStudies pertaining to age-related changes in the human jaw are very limited. Age-related changes for forensic assessments were merely based on the qualitative architecture and external geometry. With advancements in imaging technology, the paradigm has shifted and more emphasis is laid on the internal trabecular architecture, as this imparts more complexity and strength when compared to other determinants. The desired objective of this study was to draw useful associations between trabecular microarchitecture and chronological age. In this study, we characterize trabecular bone microstructure in the human mandible in 20 subjects ranging from 22 to 43 years using retrospective cone beam computed tomography image datasets. The images were post-processed via a semi- automated threshold guided approach and reconstructed using AnalyzeDirect 14.0 software to correlate trabecular number (Tb. N), trabecular thickness (Tb. Th), trabecular separation (Tb. Sp), trabecular surface density (Tb- BS/TV) and trabecular bone volume (Tb- BV/TV) with the individual’s chronological age and sex. Statistically significant negative correlations were observed in trabecular number (r =−0.489) and trabecular surface density (r = −0.527) in relation to chronological age. The characterization and quantification of the trabecular bone microarchitecture can immensely serve as a digital imprint in chronological age estimation.The aim of this study is two-fold: first, to correlate the values for each of the trabecular bone microstructure (TBM) parameters to the individual’s chronological age and sex, thereby facilitating the assessment of potential age and sex-related changes in trabecular bone microstructure parameters in the mandible; and second, to quantify the trabecular microstructural parameters in relation to chronological age. Twenty cone-beam computed tomographic (CBCT) scans were retrieved retrospectively from a database of adult patients with ages ranging in age from 22 to 43 years. In the mandible, the volume of interest included the inter-dental space between the second mandibular premolar and the first mandibular molar, as well as the trabecular space beneath and between the apices. Using the AnalyzeDirect 14.0 software, the DICOM images of CBCT scans were pre-processed, transformed, segmented using a novel semi-automatic threshold-guided method, and quantified. In addition, TBM parameters were derived, and statistical analysis was conducted using a Pearson correlation test with two tails. All parameters exhibited no statistically significant differences (p > 0.05) between chronological age and sex. Statistically significant negative correlations were found between Tb. N (r = −0.489), BS/TV (r = −0.527), and chronological age (p = 0.029 and p = 0.017, respectively). Only Tb. N and BS/TV exhibited an inverse relationship with chronological age. Numerous studies have quantified the trabecular architecture of the jaw bones, but none have found a correlation between the quantified trabecular parameters and chronological age. The digital imprints produced by radiographic imaging can serve as biological profiles for data collection.

АНАТОМО-МОРФОЛОГИЧЕСКИЙ БАЗИС ДЛЯ ДОЗИМЕТРИЧЕСКОГО МОДЕЛИРОВАНИЯ ТРАБЕКУЛЯРНОЙ КОСТИ ЧЕЛОВЕКА С ИСПОЛЬЗОВАНИЕМ СТОХАСТИЧЕСКОГО ПАРАМЕТРИЧЕСКОГО ПОДХОДА

Purpose: To create an anatomical and morphological basis for a Stochastic Parametric Skeletal Dosimetric model (SPSDmodel) for a human of different age, which includes an assessment of the parameters of the trabecular bone microstructure in the hematopoietic regions of the human skeleton. The model is necessary to estimate the doses to red bone marrow from osteotropic radionuclides (89,90Sr). The model is being created as a part of the dosimetric support for epidemiological studies of the South Ural cohorts, the members of which lived in territories radioactively contaminated in the 1950s. Materials and methods: Estimation of model parameters is based on the collection and analysis of published data. The selection of publications was made using Internet search engines: Google, PubMed, Academia, e-library, etc. Original articles in peerreviewed publications were selected, atlases, manuals, monographs and dissertations were considered. Information was collected only on healthy individuals. The collected data reffered to the following parameters of the trabecular bone: trabecular thickness, intertrabecular space, the proportion of bone in the total tissue volume. The parameters were assessed using histomorphometry and micro-CT. To make a decision about bone modeling, the data on a hematopoietic activity in it, obtained by MRI and PET, were considered. Result: Based on the results of the analysis of published information, primary data files were generated containing bibliographic data on the source of information, data on the subjects of the study and the measurement results of trabecular bone parameters. On this basis, average population estimates of the parameters were obtained and their variability (standard deviation, coefficients of variation) was estimated. Data on the duration of hematopoiesis in various parts of the skeleton and data on age-related changes in the microstructure were analyzed. The paper presents a description of a full set of parameters of the SPSD model of trabecular bones for newborns, children aged 1, 5 and 10 years, as well as for adolescents aged 15 years and adults. Conclusion: The obtained numerical values are used as input data (parameters) for generating dosimetric phantoms in voxel form. Our results will make it possible in the future to calculate conversion factors that relate the specific activity of radionuclides in the source tissue (bone trabeculae) to the dose rate in the detector tissue (red bone marrow), as well as the uncertainty of their estimates.

The effects of combined amplitude and high-frequency vibration on physically inactive osteopenic postmenopausal women.

Purpose: To evaluate whole-body vibration (WBV) osteogenic potential in physically inactive postmenopausal women using high-frequency and combined amplitude stimuli. Methods: Two-hundred fifty-five physically inactive postmenopausal women (55–75 years) with 10-year major osteoporotic fracture risk (3%–35%) participated in this 18-month study. For the first 12 months, the vibration group experienced progressive 20-min WBV sessions (up to 3 sessions/week) with rest periods (30–60 s) between exercises. Frequencies (30–50 Hz), with low (0.2–0.4 mm) and high (0.6–0.8 mm) amplitude stimuli were delivered via PowerPlate Pro5 platforms producing accelerations of (0.75–7.04 g). The last 6 months for the treatment group were a follow-up period similar to control. Serum bone remodelling markers [C-terminal crosslinked telopeptide of type-1 collagen (CTX), procollagen type-1 N-terminal propeptide (P1NP), bone alkaline phosphatase (BAP) and sclerostin] were measured at fasting. CTX and P1NP were determined by automated chemiluminescence immunoassay, bone alkaline phosphatase (BAP) by automated spectrophotometric immunoassay, and sclerostin by an enzyme-immunoassay. Bone mineral density (BMD) of the whole-body, proximal femur and lumbar vertebrae was measured by dual-energy X-ray absorptiometry (DXA). Bone microarchitecture of the distal non-dominant radius and tibia was measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: Femoral neck (p = 0.520) and spine BMD (p = 0.444) failed to improve after 12 months of WBV. Bone macro and microstructural parameters were not impacted by WBV, as well as estimated failure load at the distal radius (p = 0.354) and tibia (p = 0.813). As expected, most DXA and HR-pQCT parameters displayed age-related degradation in this postmenopausal population. BAP and CTX increased over time in both groups, with CTX more marginally elevated in the vibration group when comparing baseline changes to month-12 (480.80 pmol/L; p = 0.039) and month-18 (492.78 pmol/L; p = 0.075). However, no differences were found when comparing group concentrations only at month-12 (506.35 pmol/L; p = 0.415) and month-18 (518.33 pmol/L; p = 0.480), indicating differences below the threshold of clinical significance. Overall, HR-pQCT, DXA bone parameters and bone turnover markers remained unaffected. Conclusion: Combined amplitude and high-frequency training for one year had no ameliorating effect on DXA and HR-pQCT bone parameters in physically inactive postmenopausal women. Serum analysis did not display any significant improvement in formation and resorption markers and also failed to alter sclerostin concentrations between groups.

Bone quality in patients with osteoporosis undergoing lumbar fusion surgery: analysis of the MRI-based vertebral bone quality score and the bone microstructure derived from microcomputed tomography

Osteoporosis is a risk factor for instrumentation failure in spine surgery. Bone strength is commonly assessed by bone mineral density (BMD) as a surrogate marker. However, BMD represents only a portion of bone strength and does not capture the qualitative dimensions of bone. Recently, the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score was introduced as a novel marker of bone quality. However, it is still unclear if the VBQ score correlates with in-vivo bone microstructure. The aims of the study were (1) to demonstrate differences in MRI-based (VBQ) and in-vivo (microcomputed tomography; μCT) bone quality between osteopenic/osteoporotic and normal bone, (2) to show the correlation between VBQ, bone microstructure and volumetric BMD (vBMD), and (3) to determine the predictive value of the VBQ score for the prevalence of osteopenia/osteoporosis. Retrospective cross-sectional study. 267 patients who underwent posterior lumbar fusion surgery from 2014 to 2021 at a single academic institution. Bone biopsies were harvested intraoperatively in 118 patients. VBMD, VBQ score, and bone microstructure parameters derived from μCT. Quantitative computed tomography (QCT) measurements were performed at the lumbar spine and the L1/L2 average was used to categorize patients with a vBMD ≤120mg/cm3 as osteopenic/osteoporotic. The VBQ score was determined by dividing the median signal intensity of the L1-L4 vertebrae by the signal intensity of the cerebrospinal fluid using sagittal T1-weighted MRI scans. Intraoperative bone biopsies from the posterior superior iliac spine were obtained and evaluated with μCT. VBQ scores and μCT parameters were compared between the normal and the osteopenic/osteoporotic group. Correlations between VBQ score, μCT parameters and vBMD were assessed with Spearman's correlation (ρ). Receiver operating characteristic (ROC) analysis was performed to determine the VBQ score as a predictor for osteopenia/osteoporosis. Multiple linear regression analysis with vBMD L1/L2 as outcome was used to identify independent predictors from VBQ, μCT parameters and demographics. 267 patients (55.8% female, age 63.3 years, BMI 29.7 kg/m2; n=118 with bone biopsy) with a prevalence of osteopenia/osteoporosis of 65.2% were analyzed. In the osteopenic/osteoporotic group the VBQ score, structured model index (SMI), and trabecular separation (Tb.Sp) were significantly higher, whereas bone volume fraction (BV/TV), connectivity density (Conn.D) and trabecular number (Tb.N) were significantly lower. There were significant correlations between VBQ and μCT parameters ranging from ρ=-.387 to ρ=0.314 as well as between vBMD and μCT parameters ranging from ρ=-.425 to ρ=.421, and vBMD and VBQ (ρ=-.300, p<.001). ROC analysis discriminated osteopenia/osteoporosis with a sensitivity of 84.7% and a specificity of 40.6% at a VBQ score threshold value of 2.18. Age, BV/TV and trabecular thickness (Tb.Th), but not VBQ, were significant independent predictors for vBMD (corrected R2=0.434). This study demonstrated for the first time that the VBQ score is associated with trabecular microstructure determined by μCT. The bone microstructure and VBQ score were significantly different in patients with impaired vBMD. However, the ability to predict osteopenia/osteoporosis with the VBQ score was moderate. The VBQ score appears to reflect additional bone quality characteristics and might have a complementary role to vBMD. This enhances our understanding of the biological background of the radiographic VBQ score and might be a take-off point to evaluate the clinical utility of it as non-invasive screening tool for bone quality.

Subchondral involvement in osteonecrosis of the femoral head: insight on local composition, microstructure and vascularization

To determine changes of subchondral bone composition, micro-structure, bone marrow adiposity and micro-vascular perfusion in end-stage osteonecrosis of the femoral head (ONFH) compared to osteoarthritis (OA) using a combined in vivo and ex vivo approach. Male patients up to 70 years old referred for total hip replacement surgery for end-stage ONFH were included (n=14). Fifteen patients with OA were controls. Pre-operative MRI was used to assess bone perfusion (dynamic contrast-enhanced (DCE) sequences) and marrow fat content (chemical shift imaging). Three distinct zones of femoral head subchondral bone - necrotic, sclerotic, distant - were compared between groups. After surgery, plugs were sampled in these zones and Raman spectroscopy was applied to characterize bone mineral and organic components (old and newly-formed), and contrast-enhanced micro-computed tomography (CE-μCT) to determine bone micro-structural parameters and volume of bone marrow adipocytes, using conventional 2D histology as a reference. In the necrotic zone of ONFH patients compared to OA patients: 1) the subchondral plate did not exhibit significant changes in composition nor structure; 2) the volume fraction of subchondral trabecular bone was significantly lower; 3) type-B carbonate substitution was less pronounced, 4) collagen maturity was more pronounced; and 5) bone marrow adipocytes were significantly depleted. The sclerotic zone from the ONFH group showed greater trabecular thickness, and higher DCE-MRI AUC and Ktrans. Volume fraction of subchondral bone, trabecular number, and Kep were significantly lower in the distant zone of the ONFH group. This study demonstrated alterations of subchondral bone microstructure, composition, perfusion and/or adipose content in all zones of the femoral head.

Effects of type 2 diabetes on the viscoelastic behavior of human trabecular bone

SummaryType 2 diabetes (T2D) is a well-known disease that impaired bone mechanical properties and increases the risk of fragility fracture. The bone tissue is a viscoelastic material that means the loading rate determines its mechanical properties. This study investigates the impact of T2D on the viscoelastic properties of human bone and its association with microstructure and biochemical properties. IntroductionViscoelasticity is an important mechanical property of bone and for this the interaction of individual constituents of bone plays an important role. The viscoelastic nature of bone can be affected by aging and diseases, which can further influence its deformation and damage behavior. MethodsThe present study investigated the effects of T2D on the viscoelastic behavior of trabecular bone. The femoral heads of T2D (n = 26) and non-T2D (n = 40) individuals with hip fragility fractures were collected for this investigation. Following the micro-CT scanning of all bone samples, the stress relaxation and dynamic mechanical analysis (DMA) tests were performed to quantify the viscoelasticity of bone. Further, a correlation analysis was performed to investigate the effects of alteration in bone microstructural and biochemical parameters on viscoelasticity. ResultsThe stress relaxation and frequency sweep responses of T2D and non-T2D trabecular bone specimens were not found significantly different. However, the storage modulus, initial stiffness, and initial stress were found lower in T2D bone. The significant correlation of percentage stress relaxed is obtained between the mineral content (r= - 0.52, p-value = 0.003), organic content (r = 0.40, p-value = 0.02), and mineral-to-matrix ratio (r = - 0.43, p-value = 0.009). Further, storage and loss modulus were correlated with bone volume fraction (BV/TV) for both groups. The stress relaxation and frequency sweep characteristics were not found significantly connected with the other chemical, structural, or clinical parameters. ConclusionThis study suggests that T2D does not affect the time-dependent response of human femoral trabecular bone. The viscoelastic properties are positively correlated with organic content and negatively correlated with mineral content.

Effect of telmisartan on an experimental model of periodontitis in mice.

This study was performed to explore the impact of telmisartan on experimental periodontitis in mice, in terms of alveolar bone destruction, by using micro-computed tomography analysis. Male BALB/c mice were divided into four groups of 7 to 9 mice each: control (C) group; experimental periodontitis (E) group; experimental periodontitis-plus-telmisartan 5 mg/kg (ET5) group; and experimental periodontitis-plus-telmisartan 10 mg/kg (ET10) group. The mice in Group C were not subjected to experimental periodontitis. The other mice from Groups E, ET5 and ET10 were exposed to periodontitis. Periodontitis was induced by inoculation with Porphyromonas gingivalis. Telmisartan significantly suppressed both the reduction in alveolar bone height and increase of root exposure caused by P. gingivalis infection. When mice were treated with telmisartan, the decrease in the bone volume fraction induced by the infection was notably recovered. In addition, telmisartan reversed P. gingivalis-induced alterations in the microstructural parameters of trabecular bone, except trabecular thickness.No significant difference was evident between Groups ET5 and ET10 in both the extent of alveolar bone loss and microstructural parameters assessed, except bone volume fraction and trabecular number. Telmisartan may have potential benefits as a host modulation agent for the therapy of periodontitis.

Biodegradable magnesium implant enhances angiogenesis and alleviates medication-related osteonecrosis of the jaw in rats.

BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic medications, of which impaired angiogenesis is a key pathological alteration. Since Magnesium (Mg)-based implants possess proangiogenic effects, we hypothesized that the biodegradable Mg implant could alleviate the development of MRONJ via enhancing angiogenesis.MethodsMRONJ model was established and divided into the Veh ​+ ​Ti group (Vehicle-treated rat, with Titanium (Ti) implant), BP ​+ ​Ti group (Bisphosphonate (BP)-treated rat, with Ti implant), BP ​+ ​Mg group (BP-treated rat, with Mg implant), BP ​+ ​Mg ​+ ​SU5416 group (BP-treated rat, with Mg implant and vascular endothelial growth factor (VEGF) receptor-2 inhibitor), BP ​+ ​Mg ​+ ​BIBN group (BP-treated rat, with Mg implant and calcitonin gene-related peptide (CGRP) receptor antagonist), and BP ​+ ​Mg ​+ ​SU5416+BIBN group (BP-treated rat, with Mg implant and VEGF receptor-2 inhibitor and CGRP receptor antagonist). The occurrence of MRONJ, alveolar bone necrosis, new bone formation and vessel formation were assessed by histomorphometry, immunohistochemistry, and micro-CT analysis.ResultsEight weeks after surgery, the BP ​+ ​Mg group had significantly reduced occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and increased expressions of VEGFA and CGRP, than the BP ​+ ​Ti group. By simultaneously blocking VEGF receptor-2 and CGRP receptor, the vessel volume and new bone formation in the BP ​+ ​Mg group were significantly decreased, meanwhile the occurrence of MRONJ-like lesion and histological bone necrosis were significantly increased.ConclusionBiodegradable Mg implant could alleviate the development of MRONJ-like lesion, possibly via upregulating VEGF- and CGRP-mediated angiogenesis. Mg-based implants have the translational potential to be developed as a novel internal fixation device for patients with the risk of MRONJ.The Translational potential of this articleThis work reports a biodegradable Mg implant which ameliorates the development of MRONJ-like lesions possibly due to its angiogenic property. Mg-based implants have the potential to be developed as a novel internal fixation device for patients at the risk of MRONJ.

Comparison of cone-beam computed tomography and digital panoramic radiography for detecting peri-implant alveolar bone changes using trabecular micro-structure analysis.

ObjectivesWe compared changes in fractal dimension (FD) and grayscale value (GSV) of peri-implant alveolar bone on digital panoramic radiography (DPR) and cone-beam computed tomography (CBCT) immediately after implant surgery and 12 months postoperative.Materials and MethodsIn this retrospective study, 16 patients who received posterior mandibular area dental implants with CBCT scans taken about 2 weeks after implantation and one year after implantation were analyzed. A region of interest was selected for each patient. FDs and GSVs were evaluated immediately after implant surgery and at 12-month follow-up to examine the functional loading of the implants.ResultsThere were no significant differences between DPR and CBCT measurements of FD values (P>0.05). No significant differences were observed between FD values and GSVs calculated after implant surgery and at the 12-month follow-up (P>0.05). GSVs were not correlated with FD values (P>0.05).ConclusionThe DPR and reconstructed panoramic CBCT images exhibit similar image quality for the assessment of FD. There were no changes in FD values or GSVs of the peri-implant trabecular bone structure at the 12-month postoperative evaluation of the functional loading of the implant in comparison to values immediately after implantation. GSVs representing bone mass do not align with FD values that predict bone microstructural parameters. Therefore, GSVs and FDs should be considered different parameters for assessing bone quality.

Hops extract and xanthohumol ameliorate bone loss induced by iron overload via activating Akt/GSK3β/Nrf2 pathway

Osteoporosis is closely related to iron metabolism. This study aimed to investigate whether hops extract (HLE) and its active component xanthohumol (XAN) could ameliorate bone loss caused by iron overload, and explored its potential mechanism. Iron overload mice induced by iron dextran (ID) were used in vivo, and were treated with HLE and XAN for 3months. Bone micro-structure and bone morphology parameters were determined by Micro-CT and TRAP staining. Bone metabolism markers and oxidation indexes in serum and bone tissue were evaluated. For in vitro experiment, bone formation indexes were determined. Moreover, the expression of key proteins in protein kinase B (Akt)/glycogen synthetase kinase 3β (GSK3β)/nuclear factor E2-related (Nrf2) pathway was evaluated by Western blotting. HLE and XAN effectively improved the bone micro-structure of the femur in mice, altered bone metabolism biomarkers, and regulated the expression of proteins related to bone metabolism. Additionally, they significantly promoted cell proliferation, runt-related gene 2 (Runx2) expression, and increased ALP activity in ID-induced osteoblasts. Moreover, HLE and XAN markedly inhibited the increase of oxidative stress caused by iron overload in vivo and in vitro. Further studies showed that they significantly up-regulated the expression of p-Akt, p-GSK3β, nuclear-Nrf2, NAD(P)H:quinoneoxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1) in ID-induced osteoblasts. These findings indicated hops and xanthohumol could ameliorate bone loss induced by iron overload via activating Akt/GSK3β/Nrf2 pathway, which brought up a novel sight for senile osteoporosis therapy.

Adaptive local thresholding can enhance the accuracy of HR-pQCT-based trabecular bone morphology assessment.

High-resolution peripheral quantitative computed tomography (HR-pQCT) devices can scan extremities at bone microstructural level in vivo and are used mainly in research of bone diseases. Two HR-pQCT scanners are commercially available to date: XtremeCT (first generation) and XtremeCT-II (second generation) from Scanco Medical AG (Switzerland). Recently, we have proposed an adaptive local thresholding (AT) technique and showed that it can improve quantification accuracy of bone microstructural parameters, with visually less sharp cone-beam CT (CBCT) images providing a similar accuracy than XtremeCT. The aim of this study was to evaluate whether the AT segmentation technique could enhance the accuracy of HR-pQCT in quantifying bone microstructural images and to assess whether the agreement between XtremeCT and XtremeCT-II could be improved. Nineteen radii were scanned with three scanners from Scanco Medical AG: (1) XtremeCT at 82 μm, (2) XtremeCT-II at 60.7 μm and (3) the small animal microCT scanner VivaCT40 at 19 μm voxel size. The scans were segmented applying two different methods, once following the manufacturer standard technique (ST), and once by means of AT. Three-dimensional (3D) morphological analysis was performed on the trabecular volume of the segmented images using the manufacturer's standard software to calculate bone volume fraction (BV/TV), trabecular thickness (Tb.Th), separation (Tb.Sp) and number (Tb.N). The average accuracy of XtremeCT improved from R2=0.76 (ST) to 0.85 (AT) and reached the same level of accuracy as XtremeCT-II with ST (R2=0.86). The largest improvements were obtained for BV/TV and Tb.Th. For XtremeCT-II, mean accuracy improved slightly from R2=0.86 (ST) to 0.89 (AT). For both segmentations and both scanners, the standard section was quantified slightly more accurate than the subchondral section. The agreement between the scanners was enhanced from R2=0.89 (ST) to 0.98 (AT). In conclusion, AT can enhance the accuracy of XtremeCT to quantify distal radius bone microstructural parameters close to XtremeCT-II level and increases the agreement between the two HR-pQCT scanners. High-resolution peripheral quantitative computed tomography, segmentation, bone microstructural parameters.

Resistance to disuse-induced iron overload in Daurian ground squirrels (Spermophilus dauricus) during extended hibernation inactivity.

Iron overload occurs in disuse-induced osteoporosis. Hibernators are a natural animal model of resistance to disuse osteoporosis. We hypothesized that hibernators avoid iron overload to resist disuse-induced osteoporosis. Here, the role of iron metabolism in resistance to disuse osteoporosis was investigated by studying differences in iron content and iron metabolism in the femurs and livers of Daurian ground squirrels (Spermophilus dauricus) between the summer active and torpid states. Results showed that the femurs were generally well-maintained during torpor, with no significant differences observed in most bone microstructural parameters, except for a significantly lower (by 40%) trabecular bone connection density. Femur and liver iron concentrations were significantly lower during torpor (by 59% and 49%, respectively). Based on histological staining, livers were iron-negative and femurs showed a reduction in iron-positive area (by 83%) during torpor; The number of osteoblasts and osteoclasts showed no significant differences between the two groups. Most iron metabolism/homeostasis proteins expression levels in the femur and liver showed no significant differences between the two groups, with their stable expression likely preventing iron overload during inactivity. Higher femoral transferrin receptor 1 (TfR1) expression (by 108%) and lower liver ferritin expression (by 45%) were found in torpid squirrels. Lower liver ferritin may be related to the lower iron content, with the elevation in femoral TfR1 potentially related to restoration of bone iron levels. In conclusion, despite long periods of inactivity, iron levels in the femur and liver of squirrels were lower, bone formation and resorption were balanced and no iron overload was observed, as is found under disuse conditions in non-hibernators. Therefore, avoiding iron overload may be a potential mechanism for hibernators to avoid disuse-induced bone loss.

Correlation between genotypes with metabolic markers and microstructure of bones in children with Gitelman syndrome

To explore the correlation between the genotypes and metabolic markers and microstructure of bones in children with Gitelman syndrome (GS). For 15 children with GS and 10 healthy individuals, baseline data and bone metabolic markers including parathyroid hormone, alkaline phosphatase, osteocalcin, N-terminal propeptide of type I procollagen, beta isomer of the C-terminal telopeptide of type I collagen and 25-hydroxyvitamin D, high-resolution peripheral quantitative computed tomography indicators (volumetric bone mineral density, bone microstructure indicators) were collected. Genetic testing was carried out to determine their genotypes. The volumetric bone mineral density, bone geometry and bone microstructure parameters of the GS group were better than those of the healthy controls (P<0.05). Variants of the SLC12A3 gene were identified in 9 of the 15 patients but none of the 10 healthy controls. The phenotype of GS children is influenced by the interaction of genetic variants, though the phenotype associated with high frequency mutations showed no specificity. There is also a correlation between their genotype and the bone microstructure.

The mechanism of Epimedin B in treating osteoporosis as revealed by RNA sequencing-based analysis.

With the ageing of populations, the management of osteoporosis is a priority of society in general. Epimedin B, a major ingredient of Herba Epimedii, which has the advantages of high content and hypotoxicity has been proved to be effective in preventing osteoporosis in vitro. However, the efficacy and mechanism of Epimedin B on osteoporosis in vivo have not been well elucidated yet. This study aimed to investigate the effects and the potential mechanisms of 8-week repeated oral administration of Epimedin B (10 and 20 mg/kg/day) on a mouse osteoporosis model. Effects of Epimedin B were evaluated by examinations of serum bone turnover markers, bone mineral density, bone microstructure parameters and histopathological section. Epimedin B significantly rose N-terminal propeptide of type I procollagen (P1NP) and dropped C-telopeptide of type I collagen (CTX1). Connectivity density (Conn.D) increased significantly while structure model index (DA) decreased significantly after treated by Epimedin B. Meanwhile, Epimedin B administration significantly increased the number of trabecular bones while significantly decreased the gap between them. Overall, Epimedin B showed beneficial effects on osteoporosis. Furthermore, RNA sequencing-based analysis revealed 5 significantly down-regulated transcripts and 107 significantly up-regulated transcripts between the Epimedin B administration group and the model group. These transcripts were mapped to 15 pathways by KEGG enrichment analysis, of which PI3K-Akt signalling pathway, MAPK signalling pathway and PPAR signalling pathway were most connected to osteoporosis. To conclude, Epimedin B is effective in treating osteoporosis in mice via regulating PI3K-Akt, MAPK and PPAR signalling pathway.

The Negative Impacts of Acromegaly on Bone Microstructure Not Fully Reversible

PurposeThis study aimed to evaluate the bone turnover markers and bone microarchitecture parameters derived from high-resolution peripheral quantitative computed tomography (HR-pQCT) in active and controlled acromegaly patients.MethodsThis cross-sectional study involved 55 acromegaly patients from a tertiary hospital (23 males and 32 females, aged 45.0 ± 11.6 years). Firstly, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and markers for bone turnover were assessed. Next, we derived peripheral bone microstructure parameters and volumetric bone mineral density (vBMD) through HR-pQCT. These parameters were compared between acromegaly patients and 110 healthy controls, as well as between 27 active and 28 controlled acromegaly patients. Moreover, the relationship between GH/IGF-1 and bone microstructure parameters was analyzed through multiple linear regression.ResultsAs compared with healthy controls, acromegaly patients exhibited elevated cortical vBMD, reduced trabecular vBMD, and increased trabecular inhomogeneity in the distal radius and tibia. While controlled acromegaly patients had slower bone turnover, they did not necessarily have better bone microstructure relative to active patients in intergroup comparison. Nevertheless, multiple regression indicated that higher IGF-1 was associated with lower tibial stiffness and failure load. Additionally, males with higher IGF-1 typically had larger trabecular separation, lower trabecular number, and larger cortical pores in the radius. Moreover, patients with elevated GH typically had more porous cortical bone in the radius and fewer trabeculae in the tibia. However, the compromised bone strength in active patients was partially compensated by increased bone thickness. Furthermore, no significant linkage was observed between elevated GH/IGF-1 and the most important HR-pQCT parameters such as trabecular volumetric bone density.ConclusionAcromegaly adversely affected bone quality, even in controlled patients. As the deterioration in bone microstructure due to prolonged GH/IGF-1 exposure was not fully reversible, clinicians should be aware of the bone fragility of acromegaly patients even after they had achieved biochemical remission.