Bone Reports最新文献

Introduction

Fracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters.

Methods

The study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable.

Results

MVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 μm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 μm, p = 0.017) and by 8.73 μm (4.8 %, CI: 0.79, 16.7 μm, p = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, p = 0.011) and cortical BMD (Ct.BMD) was significantly lower by −43.6 mg/cm³ (2.6 %, CI: −77.4, −9.81 mg/cm³, p = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm³ (13.3 %, CI: 0.004, 0.04 mm³, p = 0.017) and 15.4 μm (2.9 %, CI: 0.42, 30.4 μm, p = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm⁻³ (17.8 %, CI: 0.01, 0.21 mm⁻³, p = 0.033) and vessel volume and diameter were significantly lower by −0.02 mm³ (13.7 %, CI: −0.04, −0.004 mm³, p = 0.015) and − 14.6 μm (2.8 %, CI: −29.1, −0.11 μm, p = 0.048), respectively.

Conclusions

The presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.

Type I collagen plays a pivotal role in shaping bone morphology and determining its physical properties by serving as a template for ossification. Nevertheless, the mechanisms underlying bone collagen formation, particularly the principles governing its orientation, remain unknown owing to the lack of a method that enables continuous in vivo observations. To address this challenge, we constructed a method to visualize bone collagen by tagging with green fluorescent protein (GFP) in zebrafish and observed the interactions between osteoblasts and collagen fibers during bone formation in vivo. When collagen type I alpha 2 chain (Col1a2)-GFP was expressed under the control of the osteoblast-specific promoters osx or osc in zebrafish, bone collagen was observed clearly enough to identify its localization, whereas collagen from other organs was not. Therefore, we determined that this method was of sufficient quality for the detailed in vivo observation of bone collagen. Next, bone collagen in the scales, fin rays, and opercular bones of zebrafish was observed in detail, when bone formation is more active. High-magnification imaging showed that Col1a2-GFP can visualize collagen sufficiently to analyze the collagen fiber orientation and microstructure of bones.

Furthermore, by simultaneously observation of bone collagen and osteoblasts, we successfully observed dynamic changes in the morphology and position of osteoblasts from the early stages of bone formation. It was also found that the localization pattern and orientation of bone collagen significantly differed depending on the choice of the expression promoter. Both promoters (osx and osc) used in this study are osteoblast-specific, but their Col1a2-GFP localizing regions within the bone were exclusive, with osx region localizing mainly to the outer edge of the bone and osc region localizing to the central area of the bone. This suggests the existence of distinct osteoblast subpopulations with different gene expression profiles, each of which may play a unique role in osteogenesis.

These findings would contribute to a better understanding of the mechanisms governing bone collagen formation by osteoblasts.

Filamin B (FLNB) plays an important role in skeletal development. Mutations in FLNB can lead to skeletal malformation such as an abnormal number of ossification centers, indicating that the skeletal segmentation in the embryonic period may be interfered with. We established a mouse model with the pathogenic point mutation FLNB NM_001081427.1: c.4756G > A (p.Gly1586Arg) using CRISPR-Cas9 technology. Micro-CT, HE staining and whole skeletal preparation were performed to examine the skeletal malformation. In situ hybridization of embryos was performed to examine the transcription of HOX genes during embryonic development. The expression of FLNB was downregulated in FLNB^{G1586R/G1586R} and FLNB^WT/G1586R mice, compared to FLNB^WT/WT mice. Fusions in tarsal bones were found in FLNB^{G1586R/G1586R} and FLNB^WT/G1586R mice, indicating that the skeletal segmentation was interfered with. In the embryo of FLNB^{G1586R/G1586R} mice (E12.5), the transcription levels of HOXD10 and HOXB2 were downregulated in the carpal region and cervical spine region, respectively. This study indicated that the loss-of-function mutation G1586R in FLNB may lead to abnormal skeletal segmentation, and the mechanism was possibly associated with the downregulation of HOX gene transcription during the embryonic period.

Age-associated osteoporosis (AAOP) poses a significant health burden, characterized by increased fracture risk due to declining bone mass and strength. Effective prevention and early treatment strategies are crucial to mitigate the disease burden and the associated healthcare costs. Current therapeutic approaches effectively target the individual contributing factors to AAOP. Nonetheless, the management of AAOP is complicated by the multitude of variables that affect its development. Main intrinsic and extrinsic factors contributing to AAOP risk are reviewed here, including mechanical unloading, nutrient deficiency, hormonal disbalance, disrupted metabolism, cognitive decline, inflammation and circadian disruption. Furthermore, it is discussed how these can be targeted for prevention and treatment. Although valuable as individual targets for intervention, the interconnectedness of these risk factors result in a unique etiology for every patient. Acknowledgement of the multifaceted nature of AAOP will enable the development of more effective and sustainable management strategies, based on a holistic, patient-centered approach.

In this forensic case report, we present autopsy findings from a young male in his thirties who had been self-injecting paraffin oil into his upper extremities 8 years prior to death. The injections induced an inflammatory response, leading to granuloma formation. This, in turn, resulted in severe hypercalcemia. The external autopsy examination revealed gross macroscopic ulcerations and enlargement of upper extremities, while calcifications of ligaments, heart, kidneys and dura mater was revealed on postmortem CT-scans. Histopathological examination showed extensive multiorgan metastatic calcifications in several tissues including the lungs, heart and kidney. Cause of death was estimated to be the extensive calcific deposits in the heart likely resulting in cardiac arrest. To our knowledge this is the first case reporting findings from an autopsy in which the cause of death was linked to cosmetic oil injections.

There is a wide spectrum of craniofacial bone disorders and dysplasias because embryological development of the craniofacial region is complex. Classification of craniofacial bone disorders and dysplasias is also complex because they exhibit complex clinical, pathological, and molecular heterogeneity. Most craniofacial disorders and dysplasias are rare but they present an array of phenotypes that functionally impact the orofacial complex. Management of craniofacial disorders is a multidisciplinary approach that involves the collaborative efforts of multiple professionals. This review provides an overview of the complexity of craniofacial disorders and dysplasias from molecular, clinical, and management perspectives.

Introduction

Fractures affect people's quality of life especially in the elders. One of the most important risk factors is osteoporosis. There are many screening tools to predict osteoporosis and fractures. We aimed to compare the predictive validity of three commonly used screening tools: fracture risk assessment tool (FRAX), osteoporosis self-assessment tool for Asians (OSTA) and one-minute osteoporosis risk test. Among them, OSTA and one-minute osteoporosis risk test were originally developed to predict osteoporosis risks and FRAX was to predict fracture risks.

Methods

This is an 11-year longitudinal study. We enrolled 708 senior people from health examinees in Taiwan in 2010. A standardized questionnaire and blood tests were provided. Annual telephone interview was conducted to assess the real fracture status. We calculated risk scores of FRAX, OSTA, and one-minute osteoporosis risk test and compared with real-world fracture records.

Results

The mean age of the participants were 74.9 (SD 6.4). There were 356 (50.3 %) men. From 2010 to 2020, a total of 105 (14.8 %) persons suffered from fractures. Compared to people without fractures, people with fractures had higher FRAX major osteoporotic fracture risk scores (14.0 % ± 7.6 % vs.11.3 % ± 5.7 %), higher hip fracture risk scores, and higher OSTA risk (5.9 % ± 1.4 % vs. 5.3 % ± 1.3 %). Cox regression analysis showed that hazard ratios for fracture of high FRAX risk was 1.53 (95 % confidence interval (CI) 1.05–2.21), and for high OSTA risk was 1.37 (95 % CI 1.04–1.82).

Conclusions

Only OSTA and FRAX scores were satisfactory in predicting 10-year fractures.

Objectives

Adjacent segment disc degeneration (ASDD) is one of the long-term sequelae of spinal fusion, which is more susceptible with osteoporosis. As an anti-osteoporosis drug, strontium ranelate (SR) has been reported to not only regulate bone metabolism but also cartilage matrix formation. However, it is not yet clear whether SR has a reversal or delaying effect on fusion-induced ASDD in a model of osteoporosis.

Materials and methods

Fifth three-month-old female Sprague-Dawley rats that underwent L4-L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after bilateral ovariectomy (OVX) surgery. Animals were administered vehicle (V) or SR (900 mg/kg/d) orally for 12 weeks post-PLF as follows: Sham+V, OVX + V, PLF + V, OVX + PLF + V, and OVX + PLF + SR. Manual palpation and X-ray were used to evaluate the state of lumbar fusion. Adjacent-segment disc was assessed by histological (VG staining and Scoring), histomorphometry (Disc Height, MVD, Calcification rate and Vascular Bud rate), immunohistochemical (Col-II, Aggrecan, MMP-13, ADAMTS-4 and Caspase-3), and mRNA analysis (ColI, Col-II, Aggrecan, MMP-13 and ADAMTS-4). Adjacent L6 vertebrae microstructures were evaluated by microcomputed tomography.

Results

Manual palpation and radiographs showed clear evidence of the fused segment's immobility. After 12 weeks of PLF surgery, a fusion-induced ASDD model was established. Low bone mass caused by ovariectomy can significantly exacerbate ASDD progression. SR exerted a protective effect on adjacent segment intervertebral disc with the underlying mechanism possibly being associated with preserving bone mass to prevent spinal instability, maintaining the functional integrity of endplate vascular microstructure, and regulating matrix metabolism in the nucleus pulposus and annulus fibrosus.

Discussion

Anti-osteoporosis medication SR treatments not only maintain bone mass and prevent fractures, but early intervention could also potentially delay degenerative conditions linked to osteoporosis. Taken together, our results suggested that SR might be a promising approach for the intervention of fusion-induced ASDD with osteoporosis.

The prevalence of diabetes mellitus has exhibited a notable surge in recent years, thereby augmenting the susceptibility to fractures and impeding the process of fracture healing. The primary objective of this investigation is to employ synchrotron radiation phase-contrast imaging computed tomography (SR-PCI-CT) to examine the morphological and structural attributes of different types of callus in a murine model of diabetic partial fractures. Additionally, a deep learning image segmentation model was utilized to facilitate both qualitative and quantitative analysis of callus during various time intervals. A total of forty male Kunming mice, aged five weeks, were randomly allocated into two groups, each consisting of twenty mice, namely, simple fracture group (SF) and diabetic fracture group (DF). Mice in DF group were intraperitoneally injected 60 mg/kg 1 % streptozotocin(STZ) solution for 5 consecutive days, and the standard for modeling was that the fasting blood glucose level was ≥11.1 mmol /l one week after the last injection of STZ. The right tibias of all mice were observed to have oblique fractures that did not traverse the entire bone. At three, seven, ten and fourteen days after the fracture occurred, the fractured tibias were extracted for SR-PCI-CT imaging and histological analysis. Furthermore, a deep learning image segmentation model was devised to automatically detect, categorize and quantitatively examine different types of callus. Image J software was utilized to measure the grayscale values of different types of callus and perform quantitative analysis. The findings demonstrated that:

• 1)

  SR-PCI-CT imaging effectively depicted the morphological attributes of different types of callus of fracture healing. The grayscale values of different types of callus were significantly different(P < 0.01).

• 2)

  In comparison to the SF group, the DF group exhibited a significant reduction in the total amount of callus during the same period (P < 0.01). Additionally, the peak of cartilage callus in the hypertrophic phase was delayed.

• 3)

  Histology provides the basis for training algorithms for deep learning image segmentation models. The deep-learning image segmentation models achieved accuracies of 0.69, 0.81 and 0.733 for reserve/proliferative cartilage, hypertrophic cartilage and mineralized cartilage, respectively, in the test set. The corresponding Dice values were 0.72, 0.83 and 0.76, respectively.

In summary, SR-PCI-CT images are close to the histological level, and a variety of cartilage can be identified on synchrotron radiation CT images compared with histological examination, while artificial intelligence image segmentation model can realize automatic analysis and data generation through deep learning, and further determine the objectivity and accuracy of SR-PCI-CT in identi