Bone Matrix Research Articles

A proposal for the combined analysis of bone quantity and quality of human cortical bone by quasi-brittle fracture mechanics

Quasi-brittle fracture mechanics is used to evaluate fracture of human cortical bone in aging. The approach is demonstrated using cortical bone bars extracted from one 92-year-old human male cadaver. In-situ fracture mechanics experiments in a 3D X-ray microscope are conducted. The evolution of the fracture process zone is documented. Fully developed fracture process zone lengths at peak load are found to span about three osteon diameters. Crack deflection and arrest at cement lines is a key process to build extrinsic toughness. Strength and toughness are found as size-dependent, not only for laboratory-scale experimental specimens but also for the whole femur. A scaling law for the length fracture process zone is used. Then, size-independent, tissue fracture properties are calculated. Linear elastic fracture mechanics applied to laboratory beam specimens underestimates the tissue toughness by 60%. Tissue fracture properties are used to predict the load capacity of the femur in bending within the range of documented data. The quasi-brittle fracture mechanics approach allows for the assessment of the combined effect of bone quantity and bone quality on fracture risk. However, further work is needed considering a larger range of subjects and in the model validation at the organ length scale.

Preparation of decellularized bone graft material with supercritical carbon dioxide extraction technique.

To evaluate the immunogenicity and osteogenic ability of animal-derived bone graft material decellularized with supercritical carbon dioxide. Porcine femurs were randomly divided into two groups after preliminary treatment, and decellularized with conventional method (conventional control group) or supercritical carbon dioxide (experimental group). Clearance rate of galactose-α-1, 3-galactose (α-Gal) and residual DNA of the two groups were analyzed to assess the immunogenicity of the xenogenic materials. Clearance rate of α-Gal was determined by enzyme-linked immunosorbent assay and residual DNA was detected by fluorescence method. Nine SPF-grade male athymic nude mice of 6 weeks old were randomly divided into experimental group, conventional control group and positive control group. Samples were implanted over biceps femoris muscle of athymic nude mice, the explants were collected 4 weeks post implantation, hematoxylin and eosin (HE) staining and immunohistochemistry were applied to determine the osteogenic ability and bone tissue-associated protein expressions of the implants. The clearance rates of α-Gal antigen in the experimental group and the conventional control group were (99.09±0.26)% and (30.18±2.02)%, respectively (t=58.67, P<0.01). The residual DNA of the experimental group, the conventional control group and the positive control group were (13.49±0.07) ng/mg, (15.20±0.21) ng/mg and (14.70±0.17) ng/mg, the residual DNA in the experimental group was significantly lower than that in the conventional control group (t=－13.41, P<0.01) and the positive control group (t=－11.30, P<0.01). HE staining showed that multiple bone formation centers with active osteogenesis and rich bone marrow were observed in experimental group 4 weeks after implantation, only a small number of bone formation centers were observed in the conventional control group and the positive control group, with no obvious osteoblasts present. Immunohistochemistry results indicated that the expressions of alkaline phosphatase, Runt-related transcription factor 2, typeⅠcollagen and osteocalcin in the experimental group showed an increasing trend compared with those in the conventional control group and the positive control group. Compared with clinically used demineralized bone matrix and bone graft material decellularized with conventional method, bone graft material decellularized with supercritical carbon dioxide exhibits lower immunogenicity and better osteogenic ability.

Bone-seeking tumor cells alter bone material quality parameters on the nanoscale in mice

Bone metastases related to breast and prostate cancer present with multiple challenges and skeletal related events like fragility fractures impair the quality of life of the patients significantly. To determine local alterations in bone material quality with bone metastasis, we subjected murine tibial specimens, generated after intratibial injections of either RM-1 prostate cancer cells or EO771 breast cancer cells into male and female mice respectively, to high-resolution imaging modalities. Small and wide-angle X-ray scattering showed unaltered mineral characteristics in the more osteosclerotic prostate cancer model, while the quantification of calcium weight percentage via backscattered electron microscopy determined minor differences along the perilacunar bone matrix. Further analyses of mineral and collagen characteristics were performed using Raman spectroscopy and focused ion beam electron microscopy. Our study indicates that alterations in nanochannel properties occur due to the presence of bone seeking tumor cells with more prevalent nanopores in the perilacunar matrix.

Research progress on the regulatory cell death of osteoblasts in periodontitis

Periodontitis is a chronic inflammatory disease characterized by progressive destruction of alveolar bone. The most critical mechanism underlying alveolar bone destruction is the imbalance of bone homeostasis, where osteoblast-mediated bone matrix synthesis plays an important role in regulating bone homeostasis. Regulated cell death is instrumental in both the inflammatory microenvironment and the regulation of bone homeostasis. Chronic inflammation, oxidative stress, and other factors can be directly involved in mitochondrial and death receptor-mediated signaling pathways, modulating B-cell lymphoma 2 family proteins and cysteine aspartic acid specific protease (caspase) activity, thereby affecting osteoblast apoptosis and alveolar bone homeostasis. Chronic inflammation and cellular damage induce osteoblast necroptosis via the RIPK1/RIPK3/MLKL signaling pathway, exacerbating the inflammatory response and accelerating alveolar bone destruction. Stimuli such as pathogenic microorganisms and cellular injury may also activate caspase-1-dependent or independent signaling pathways and gasdermin D family proteins, promoting osteoblast pyroptosis and releasing pro-inflammatory cytokines to mediate alveolar bone damage. Iron overload and lipid peroxidation in periodontitis can trigger ferroptosis in osteoblasts, impacting their survival and function, ultimately leading to bone homeostasis imbalance. This article focuses on the mechanism of periodontal disease affecting bone homeostasis through regulatory cell death, aiming to provide research evidence for the treatment of periodontitis and alveolar bone homeostasis imbalance.

Potential of combined red and near-infrared photobiomodulation to mitigate pro-osteoclastic and inflammatory gene expression in human mandibular osteogenic cells

Appropriate regeneration of jawbone after dental or surgical procedures relies on the recruitment of osteoprogenitor cells able to differentiate into matrix-producing osteoblasts. In this context, photobiomodulation (PBM) has emerged as promising therapy to improve tissue regeneration and to facilitate wound healing processes. The aim of this study was to determine the effect of PBM on human osteoprogenitor cells isolated from mandibular trabecular bone.Bone marrow stromal cell cultures were established from 4 donors and induced toward osteogenic differentiation for 14 days in a standard osteogenic assay. Cells were irradiated with a combined red/near-infrared (NIR) laser following different schedules and expression of osteogenic, matrix-related, osteoclastogenic and inflammatory genes was analyzed by quantitative PCR.Gene expression analysis revealed no overall effects of PBM on osteogenic differentiation. However, a statistically significant reduction was observed in the transcripts of COL1A1 and MMP13, two important genes involved in the bone matrix homeostasis. Most important, PBM significantly downregulated the expression of RANKL, IL6 and IL1B, three genes that are involved in both osteoclastogenesis and inflammation.In conclusion, PBM with a red/NIR laser did not modulate the osteogenic phenotype of mandibular osteoprogenitors but markedly reduced their expression of matrix-related genes and their pro-osteoclastogenic and pro-inflammatory profile.

Demineralized, Freeze-Dried Allogeneic Bone Blocks With Suture Fixation Technique for Reconstruction of Maxillary Alveolar Bone Deficiency: A Case Series.

This study aims to evaluate the clinical outcomes of using demineralized, freeze-dried allogeneic bone blocks (DFDABB) combined with the periosteal vertical mattress suture (PVMS) technique for the reconstruction of severe horizontal alveolar bone deficiencies in the maxilla. In continuous horizontal maxillary defects cases, bone augmentation was performed using DFDABB and deproteinized bovine bone matrix (DBBM) filling the interstice. Subsequently, a resorbable collagen membrane was carefully placed over the graft surface, and both the membrane and bone graft were firmly secured using the PVMS technique. Linear changes were assessed through superimposed cone-beam computerized tomography scans obtained before the operation and after a healing period of 6-10 months. A total of 7 female patients with 10 bone blocks and 13 implants were included in this study. One of the wounds was slightly ruptured postoperatively without infection, and all implants showed successful osseointegration. The average alveolar ridge width at a point 5 mm below the crest was 4.52 ± 2.03 mm before bone graft and 9.79 ± 1.57 mm after implantation with an average increase of 5.26 ± 1.97 mm. Similarly, at a point 10 mm below the crest, the pregraft alveolar ridge width measured 7.23 ± 3.60 mm, and postimplantation, it expanded to 11.81 ± 2.90 mm, showing an average gain of 4.58 ± 2.01 mm. This case series demonstrates the successful application of DFDABB combined with the PVMS technique to achieve adequate bone width for implantation at severe continuous horizontal bone deficiency of the maxilla. DFDABB with the PVMS technique resulted in superior horizontal bone gain during maxillary bone augmentation with horizontal continuity deficiency. However, further studies are necessary to validate these findings.

Mechanobiological cues to bone cells during early metastasis drive later osteolysis: a computational mechanoregulation framework prediction

Bone cells contribute to tumour metastasis by producing biochemical factors that stimulate tumour cell homing and proliferation, but also by resorbing bone matrix (osteolysis) that releases further stimulatory factors for tumour growth in a vicious cycle. Changes in the local mechanical environment of bone tissue occur during early metastasis, which might activate mechanobiological responses by resident bone cells (osteocytes) to activate resorption (osteoclasts) and thereby contribute to tumour invasion. The objective of this study is to investigate whether bone osteolysis is driven by early changes in the bone mechanical environment during metastasis by (a) implementing subject-specific FE models of metastatic femora to predict the mechanical environment within bone tissue during early metastasis (3-weeks after tumour inoculation) and then (b) applying mechanoregulation theory to predict bone tissue remodelling as a function of the evolving mechanical environment within bone tissue during breast cancer-bone metastasis. We implemented a global resorption rate derived from an experimental model, but the mechanoregulation algorithm predicted localised bone loss in the greater trochanter region, the same region where osteolysis was prevalent after three weeks of metastasis development in the animal model. Moreover, the mechanical environment evolved in a similar manner to that reported in separate subject-specific finite element models of these same animals by 6 weeks. Thus, we propose that early changes in the physical environment of bone tissue during metastasis may elicit mechanobiological cues for bone cells and activate later osteolytic bone destruction.

Bone development by Hedgehog and Wnt signaling, Runx2, and Sp7.

Hedgehog and canonical Wnt signaling pathways and the transcription factors Runx2 and Sp7 are essential for osteoblast differentiation. Ihh is necessary for the commitment of perichondrial mesenchymal cells to Runx2+ osteoprogenitors and for the formation of the bone collar and primary spongiosa. Runx2 is needed for osteoblast differentiation during both endochondral and intramembranous ossification. It regulates the commitment of mesenchymal cells to osteoblast-lineage cells and their proliferation by inducing the expression of Hedgehog, Fgf, Wnt, Pthlh signaling pathway genes, and Dlx5. The Runx2-induced expression of Fgfr2 and Fgfr3 is important for the proliferation of osteoblast-lineage cells. Runx2 induces Sp7 expression and Runx2+ osteoprogenitors become Runx2+Sp7+ preosteoblasts. Runx2, Sp7, and canonical Wnt signaling induce the differentiation of preosteoblasts into osteoblasts. Canonical Wnt signaling, but not Sp7, enhances the proliferation of osteoblast-lineage cells. In mature osteoblasts, Runx2 plays an important role in the expression of major bone matrix protein genes, including Col1a1, Col1a2, Spp1, Ibsp, and Bglap/Bglap2. The canonical Wnt signaling pathway is also crucial for bone formation by mature osteoblasts. Sp7 is needed for osteocytes to acquire a sufficient number of processes and a reduction in these processes results in osteocyte apoptosis and cortical porosity.

Herbal medicine Ninjinyoeito inhibits RANKL-induced osteoclast differentiation and bone resorption activity by regulating NF-κB and MAPK pathway

ObjectivesOsteoporosis is a systemic bone metabolism disorder characterized by decreased bone mass and strength. Osteoclasts (OCs) are giant multinucleated cells that regulate bone homeostasis by degrading bone matrix. Excessive OC differentiation and activity can lead to serious bone metabolic disorders including osteoporosis. Current treatments, including antiresorptive drugs, exert considerable adverse effects, including jaw osteonecrosis. Herbal medicines, such as Ninjinyoeito (NYT), may also offer efficacy, but with fewer adverse effects. In this study, we investigated NYT's effects on osteoclastogenesis. MethodsTartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were performed to examine NYT's effects on OC differentiation and function. OC-related gene expression at mRNA and protein levels was investigated to confirm NYT's inhibitory action against osteoclastogenesis. We also demonstrated involvement of signaling pathways mediated by IκBα and mitogen-activated protein kinases (MAPK) [extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38] and showed nuclear translocation of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) and nuclear factor kappa B (NF-κB) p65 during osteoclastogenesis. ResultsTRAP staining and bone resorption assays confirmed that NYT significantly inhibited OC differentiation and function. Western blot and RT-PCR results showed that NYT ameliorated osteoclastogenesis by suppressing mRNA and protein level expression of OC-related genes. Moreover, blots and immunocytochemistry (ICC) data clarified that NYT abrogates signaling pathways mediated by IκBα and MAPK (ERK, JNK, p38), and demonstrated nuclear translocation of NFATc1 and NF-κB p65 during OC differentiation. ConclusionsThese findings suggest NYT is an alternative therapeutic candidate for treating osteoporosis.

Loss of Hdac4 in Osteoprogenitors Impairs Postnatal Trabecular and Cortical Bone Formation, Resulting in a Dwarfism and Osteopenia Phenotype in Mice

HDAC4 is a class II histone deacetylation protein with a well-characterized role in chondrocyte differentiation and skeletal development, and dysregulated expression or haploinsufficiency of Hdac4 leads to skeletal formation and malformation disorders. The early lethality of hdac4 ablation mice hindered further investigation of its role in postnatal bone growth and development. Therefore, this study aims to investigate the significant role of Hdac4 in postnatal endochondral bone development using two mouse models with conditional deletion of Hdac4 in Sp7-expressing osteoprogenitors or chondrocytes and monitored postnatal bone development. The phenotype of Acan-CreERT2; Hdac4fl/fl mice largely resembled that of conventional Hdac4-/- mice. But phenotypic characterizations of mice with Hdac4 inactivation in Sp7-expressing osteoprogenitors (Sp7-Cre; Hdac4fl/fl) showed dwarfism with body and limb shortening and remarkable skeletal defects. Micro-computed tomography analysis of tibias further demonstrated that loss of Hdac4 expression impaired bone formation and microarchitecture, mainly characterized by dysplasia of trabecular and cortical bone in young mice. Our in vivo and in vitro data support a crucial role for Hdac4 in regulating osteoblast proliferation and differentiation, bone matrix protein production, angiogenesis, and ultimately trabecular and cortical bone formation. Moreover, RNA-seq analysis implicated Hdac4 in the regulation of key genes and pathways necessary to affect the accumulation of extracellular matrix, biological processes related to signal transduction, and skeletal growth. Collectively, our data show that postnatal expression of Hdac4 in Sp7-expressing osteoprogenitors provides essential regulatory oversight of endochondral bone formation, bone morphology, and homeostasis.

Microbiome-induced increases and decreases in bone matrix strength can be initiated after skeletal maturity.

Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n= 143 total, n= 12-17/group/sex) were allocated into five study groups: (1) Unaltered, (2) Continuous (dosing 4-24weeks of age), (3) Delayed (dosing only 16-24weeks of age), (4) Initial (dosing 4-16weeks of age, suspended at 16weeks), and (5) Reconstituted (dosing from 4-16weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24weeks of age. In males, bone matrix strength in the femur was 25%-35% less than expected by geometry in mice from the Continuous (p = 0.001), Delayed (p = 0.005), and Initial (p = 0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota led to a bone matrix strength similar to Unaltered animals (p = 0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating a sex-dependent response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed with Raman spectroscopy. Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16weeks) was small; suggesting that microbiome-induced changes in bone matrix occurred without osteoblast/osteoclast turnover through a yet unidentified mechanism. These findings provide evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.

Myoblast-Derived Galectin 3 Impairs the Early Phases of Osteogenesis Affecting Notch and Akt Activity.

Galectin-3 (Gal-3) is a pleiotropic lectin produced by most cell types, which regulates multiple cellular processes in various tissues. In bone, depending on its cellular localization, Gal-3 has a dual and opposite role. If, on the one hand, intracellular Gal-3 promotes bone formation, on the other, its circulating form affects bone remodeling, antagonizing osteoblast differentiation and increasing osteoclast activity. From an analysis of the secretome of cultured differentiating myoblasts, we interestingly found the presence of Gal-3. After that, we confirmed that Gal-3 was expressed and released in the extracellular environment from myoblast cells during their differentiation into myotubes, as well as after mechanical strain. An in vivo analysis revealed that Gal-3 was triggered by trained exercise and was specifically produced by fast muscle fibers. Speculating a role for this peptide in the muscle-to-bone cross talk, a direct co-culture in vitro system, simultaneously combining media that were obtained from differentiated myoblasts and osteoblast cells, confirmed that Gal-3 is a mediator of osteoblast differentiation. Molecular and proteomic analyses revealed that the secreted Gal-3 modulated the biochemical processes occurring in the early phases of bone formation, in particular impairing the activity of the STAT3 and PDK1/Akt signaling pathways and, at the same time, triggering that one of Notch. Circulating Gal-3 also affected the expression of the most common factors involved in osteogenetic processes, including BMP-2, -6, and -7. Intriguingly, Gal-3 was able to interfere with the ability of differentiating osteoblasts to interact with the components of the extracellular bone matrix, a crucial condition required for a proper osteoblast differentiation. All in all, our evidence lays the foundation for further studies to present this lectin as a novel myokine involved in muscle-to-bone crosstalk.

Evaluation of the effect of tartrazine on the offspring rats in an in vivo experimental model

AbstractTartrazine, an azo dye prevalent in pharmaceuticals and food items, was investigated for its impact on fetal development, specifically examining visceral and skeletal abnormalities in rat offspring exposed to daily oral doses throughout pregnancy. Fourteen pregnant rats were randomly assigned to control and tartrazine groups (seven animals each), with tartrazine administered via oral gavage at 7.5 mg/kg throughout gestation. Offspring were categorized by gender for histopathological and genetic analysis of visceral structures. Bone quality and fracture resistance assessments involved micro‐CT, Raman spectroscopy, and biomechanical testing. Results highlighted distinct internal organ tissue differences in the tartrazine group, notably increased hemorrhagic and inflammatory cell infiltration, degeneration, and vacuolization compared to controls. Gender‐specific alterations in mRNA levels of IL‐6, IL‐1β, TNF‐α, and TRPM2 genes (p &lt; .001) were also noted. Moreover, tartrazine‐exposed groups exhibited reduced trabecular thickness, bone volume, and significant alterations in bone matrix composition and quality alongside significant decreases in fracture resistance (p &lt; 0.05). This study concludes that intrauterine exposure to tartrazine can result in adverse impacts on organ and bone development in rat offspring.

Evaluation of the Regenerative Capacity of Demineralized Bone Matrix vs Fat Graft in Alveolar Cleft Model in Albino Rats.

This study was performed to evaluate the regenerative capacity of demineralized bone matrix vs fat graft, both guided by pericardium membrane in alveolar cleft model in albino rats. A total of 72 rats were required in this study. A surgical bone defect with a 7 mm length × 4 mm width × 3 mm depth was created as a model of an alveolar cleft, then the rats were divided randomly into four equal groups each group contained 18 rats: control group (defect only), the membrane group (the defect was covered by the pericardium membrane), the demineralized bone matrix (DBM) group (the defect was filled with DBM guided by pericardium membrane) and fat group (the defect was filled with a fat graft guided by the pericardium membrane). Around 6 rats from each group were euthanized after 2, 4, and 8 weeks. Skulls were scanned with cone beam computed tomography (CBCT) and harvested for histological evaluation with routine H&E immunohistochemical stains (Anti-osteocalcin and Anti-Wnt5a). The data was recorded and statistically analyzed by a two-way ANOVA. The study showed a notable formation of new bone, and expression of OCN and Wnt5a were notably increased by time in the fat group. However, the density of bone grafts and OCN and Wnt5a expression decreased with time in the DBM group. Control and membrane groups showed negative OCN and Wnt5a immune-reactivity in the cleft site. Fat graft results were superior to DBM results with regard to mucosal closure and accelerated bone regeneration, and may represent an effective treatment for alveolar cleft reconstruction. Finding an inexpensive, accessible, biocompatible and easily manipulated treatment for craniofacial reconstruction and fat graft fulfilled the desired aims. Further investigations with prolonged evaluation periods are needed. How to cite this article: Abdel Raouf E, Elsherbini AM, Abdel Salam Yousef Y, et al. Evaluation of the Regenerative Capacity of Demineralized Bone Matrix vs Fat Graft in Alveolar Cleft Model in Albino Rats. J Contemp Dent Pract 2024;25(6):554-562.

Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.

Runx2 (runt related transcription factor 2) and Sp7 (Sp7 transcription factor 7) are crucial transcription factors for bone development. The cotranscription factor Cbfb (core binding factor beta), which enhances the DNA-binding capacity of Runx2 and stabilizes the Runx2 protein, is necessary for bone development. Runx2 is essential for chondrocyte maturation, and Sp7 is partly involved. Runx2 induces the commitment of multipotent mesenchymal cells to osteoblast lineage cells and enhances the proliferation of osteoprogenitors. Reciprocal regulation between Runx2 and the Hedgehog, fibroblast growth factor (Fgf), Wnt, and parathyroid hormone-like hormone (Pthlh) signaling pathways and Dlx5 (distal-less homeobox 5) plays an important role in these processes. The induction of Fgfr2 (Fgf receptor 2) and Fgfr3 expression by Runx2 is important for the proliferation of osteoblast lineage cells. Runx2 induces Sp7 expression, and Runx2+ osteoprogenitors become Runx2+Sp7+ preosteoblasts. Sp7 induces the differentiation of preosteoblasts into osteoblasts without enhancing their proliferation. In osteoblasts, Runx2 is required for bone formation by inducing the expression of major bone matrix protein genes, including Col1a1 (collagen type I alpha 1), Col1a2, Spp1 (secreted phosphoprotein 1), Ibsp (integrin binding sialoprotein), and Bglap (bone gamma carboxyglutamate protein)/Bglap2. Bglap/Bglap2 (osteocalcin) regulates the alignment of apatite crystals parallel to collagen fibrils but does not function as a hormone that regulates glucose metabolism, testosterone synthesis, and muscle mass. Sp7 is also involved in Co1a1 expression and regulates osteoblast/osteocyte process formation, which is necessary for the survival of osteocytes and the prevention of cortical porosity. SP7 mutations cause osteogenesis imperfecta in rare cases. Runx2 is an important pathogenic factor, while Runx1, Runx3, and Cbfb are protective factors in osteoarthritis development.

Serum Vitamin D and Osteocalcin for Assessment of Bone Mineral Metabolism: A Comparison of Children with Steroid-Sensitive and Resistant Nephrotic Syndrome

Background Long-term corticosteroid use decreases osteoblastic activity and bone matrix formation. Osteocalcin (OC), a marker of bone turnover, is more sensitive than alkaline phosphatase in indicating bone matrix synthesis. Materials and Methods The cross-sectional study was done from January to September 2021; a total of 62 (40 males, 22 females) children (2–18 years) with nephrotic syndrome in disease remission were enrolled. Thirty-two had steroid-sensitive nephrotic syndrome (SSNS), and 30 had steroid-resistant nephrotic syndrome (SRNS). Children who had received daily steroids or high doses of vitamin D within the previous three months were excluded. The primary objective of this study was to assess bone mineral metabolism by measuring vitamin D, parathyroid hormone (PTH), and osteocalcin levels. Results In children with SSNS, 46.8% had vitamin D insufficiency, 21.9% vitamin D deficiency, and median vitamin D levels were 28.4 ng/mL; in the SRNS group, 40% had insufficiency, 33.4% deficiency, and vitamin D levels were 26.6 ng/mL. The median steroid dose used in the previous 6 months was significantly higher in the SRNS patients, 0.63 (0.35, 0.77) mg/kg on alternate days compared to SSNS, 0.50 (0.32, 0.60) mg/kg (p = 0.02). Median serum OC levels were lower in SRNS 20.4 (10.8, 33.5) ng/mL compared to SSNS, 35.6 (22.5, 42.7) ng/mL (p = 0.004). Conclusion Bone metabolism is negatively affected in children with nephrotic syndrome, especially in those with SRNS and must continue to be vitamin D insufficient despite routine supplementation; serum OC appears to be a promising marker for this evaluation.

Bone mechanical properties were altered in a mouse model of multiple myeloma bone disease

Multiple myeloma bone disease (MMBD) is characterized by the growth of malignant plasma cells in bone marrow, leading to an imbalance in bone (re)modeling favoring excessive resorption. Loss of bone mass and altered microstructure characterize MMBD in humans and preclinical animal models, although, no study to date has examined bone composition or material properties. We hypothesized that MMBD alters bone composition, mineral crystal properties and mechanical properties in the MOPC315.BM.Luc model after intra-tibial injection of myeloma cells and three weeks of daily in vivo tibial loading. Decreased cortical bone elastic modulus and hardness measured by nanoindentation of tibiae were observed in MM-injected mice compared to PBS-injected mice, whereas cortical bone composition, mineral crystal properties measured by Fourier-transform infrared imaging or small angle X-ray scattering, respectively remained unchanged. However, MM-injected mice had thinner cancellous bone mineral particles compared to PBS-injected mice. Mechanical loading did not lead to altered cortical bone composition, mineral structure, or mechanical properties in the context of MM. Unexpectedly, we observed the intra-tibial injection itself altered the material composition of bone, manifested by increased matrix mineralization and crystal size of the hydroxyapatite crystals in the bone matrix. In conclusion, our data suggest that mechanical stimuli can be used as an adjuvant bone anabolic therapy in patients with MMBD to rebuild bone with unaltered composition and mineral structure to reduce subsequent fracture risk.

Is core decompression and bone marrow concentrate with demineralized bone matrix and platelet-rich fibrin suitable for treating femoral head osteonecrosis?

Is core decompression and bone marrow concentrate with demineralized bone matrix and platelet-rich fibrin suitable for treating femoral head osteonecrosis?

In Vivo Assessment of a Triple Periodic Minimal Surface Based Biomimmetic Gyroid as an Implant Material in a Rabbit Tibia Model.

Biomimetic approaches to implant construction are a rising frontier in implantology. Triple Periodic Minimal Surface (TPMS)-based additively manufactured gyroid structures offer a mean curvature of zero, rendering this structure an ideal porous architecture. Previous studies have demonstrated the ability of these structures to effectively mimic the mechanical cues required for optimal implant construction. The porous nature of gyroid materials enhances bone ingrowth, thereby improving implant stability within the body. This enhancement is attributed to the increased surface area of the gyroid structure, which is approximately 185% higher than that of a dense material of the same form factor. This larger surface area allows for enhanced cellular attachment and nutrient circulation facilitated by the porous channels. This study aims to evaluate the biological performance of a gyroid-based Ti6Al-4V implant material compared to a dense alloy counterpart. Cellular viability was assessed using the lactate dehydrogenase (LDH) assay, which demonstrated that the gyroid surface allowed marginally higher viability than dense material. The in vivo integration was studied over 6 weeks using a rabbit tibia model and characterized using X-ray, micro-CT, and histopathological examination. With a metal volume of 8.1%, the gyroid exhibited a bone volume/total volume (BV/TV) ratio of 9.6%, which is 11-fold higher than that of dense metal (0.8%). Histological assessments revealed neovascularization, in-bone growth, and the presence of a Haversian system in the gyroid structure, hinting at superior osteointegration.

Tough Cortical Bone-Inspired Tubular Architected Cement-Based Material with Disorder.

Cortical bone is a tough biological material composed of tube-like osteons embedded in the organic matrix surrounded by weak interfaces known as cement lines. The cement lines provide a microstructurally preferable crack path, hence triggering in-plane crack deflection around osteons due to cement line-crack interaction. Inspired by this toughening mechanism and facilitated by a hybrid (3D-printing/casting) process, the study engineers architected tubular cement-based materials with the stepwise cracking toughening mechanism, that enables a non-brittle fracture. Using experimental and theoretical approaches, the study demonstrates the competition between tube size and shape on stress intensity factor from which engineering stepwise cracking can emerge. Two competing mechanisms, both positively and negatively affected by the growing tube size, arise to significantly enhance the overall fracture toughness by up to 5.6-fold compared to the monolithic brittle counterpart without sacrificing the specific strength. This is enabled by crack-tube interaction and engineering the tube size, shape, and orientation, which promotes rising resistance-curves (R-curve). "Disorder" curves and statistical mechanics parameters are proposed for the first time to quantitatively characterize the degree of disorder for describing the representation of the architected arrangement of materials in lieu of otherwise inadequate "periodicity" classification and misperceiveddisorder parameters (perturbation and Voronoi tessellation methods).