Bone Formation Rate Research Articles

Cellular and Molecular Mechanisms Associating Obesity to Bone Loss.

Obesity is an alarming disease that favors the upset of other illnesses and enhances mortality. It is spreading fast worldwide may affect more than 1 billion people by 2030. The imbalance between excessive food ingestion and less energy expenditure leads to pathological adipose tissue expansion, characterized by increased production of proinflammatory mediators with harmful interferences in the whole organism. Bone tissue is one of those target tissues in obesity. Bone is a mineralized connective tissue that is constantly renewed to maintain its mechanical properties. Osteoblasts are responsible for extracellular matrix synthesis, while osteoclasts resorb damaged bone, and the osteocytes have a regulatory role in this process, releasing growth factors and other proteins. A balanced activity among these actors is necessary for healthy bone remodeling. In obesity, several mechanisms may trigger incorrect remodeling, increasing bone resorption to the detriment of bone formation rates. Thus, excessive weight gain may represent higher bone fragility and fracture risk. This review highlights recent insights on the central mechanisms related to obesity-associated abnormal bone. Publications from the last ten years have shown that the main molecular mechanisms associated with obesity and bone loss involve: proinflammatory adipokines and osteokines production, oxidative stress, non-coding RNA interference, insulin resistance, and changes in gut microbiota. The data collection unveils new targets for prevention and putative therapeutic tools against unbalancing bone metabolism during obesity.

GOING LOW: LOW MODULUS GRAFT-FREE 3D-PRINTED TITANIUM INTERBODY CAGES SHOW COMPARABLE BONE FORMATION TO PEEK WITH GRAFT

Polyetheretherketone (PEEK) interbody fusion cages combined with autologous bone graft is the current clinical gold standard treatment for spinal fusion, however, bone graft harvest increases surgical time, risk of infection and chronic pain. We describe novel low-stiffness 3D Printed titanium interbody cages without autologous bone graft and assessed their biological performance in a pre-clinical in vivo interbody fusion model in comparison to the gold standard, PEEK with graft.Titanium interbody spacers were 3D Printed with a microporous (Ti1: <1000μm) and macroporous (Ti2: >1000μm) design. Both Ti1 and Ti2 had an identical elastic modulus (stiffness), and were similar to the elastic modulus of PEEK. Interbody fusion was performed on L2-L3 and L4-L5 vertebral levels in 24 skeletally mature sheep using Ti1 or Ti2 spacers, or a PEEK spacer filled with iliac crest autograft, and assessed at 8 and 16 weeks. We quantitatively assessed bone fusion, bone area, mineral apposition rate and bone formation rate. Functional spinal units were biomechanically tested to analyse range of motion, neutral zone, and stiffness. Results: Bone formation in macroporous Ti2 was significantly greater than microporous Ti1 treatments (p=.006). Fusion scores for Ti2 and PEEK demonstrated greater rates of bone formation from 8 to 16 weeks, with bridging rates of 100% for Ti2 at 16 weeks compared to just 88% for PEEK and 50% for Ti1. Biomechanical outcomes significantly improved at 16 versus 8 weeks, with no significant differences between Ti and PEEK with graft.This study demonstrated that macroporous 3D Printed Ti spacers are able to achieve fixation and arthrodesis with complete bone fusion by 16 weeks without the need for bone graft. These significant data indicate that low-modulus 3D Printed titanium interbody cages have similar performance to autograft-filled PEEK, and could be reliably used in spinal fusion avoiding the complications of bone graft harvesting.

Type 1 diabetes mellitus leads to gingivitis and an early compensatory increase in bone remodeling.

Type 1 diabetes mellitus (T1DM) and periodontitis have long been thought to be biologically connected. Indeed, T1DM is a risk factor for periodontal disease. With the population of diabetic individuals growing, it is more important than ever to understand the negative consequences of diabetes on the periodontium and the mechanisms. The aim of this study was to find out the early effects of T1DM on the periodontium without any experimentally induced periodontitis. We established the streptozotocin (STZ)-induced diabetic mouse model and examined the periodontium 8weeks later by histology, molecular and cellular assays. Microcomputed tomographic (𝜇CT) imaging and in vivo fluorochrome labeling were also used to quantify bone volume and mineral apposition rates (MAR). The histologic appearance of epithelium tissue, connective tissue, and periodontal ligament in the diabetic condition was comparable with that of control mice. However, immune cell infiltration in the gingiva was dramatically elevated in the diabetic mice, which was accompanied by unmineralized connective tissue degeneration. Bone resorption activity was significantly increased in the diabetic mice, and quantitative 𝜇CT demonstrated the bone volume, the ratio of bone volume over tissue volume, and cemento-enamel junction to alveolar bone crest (CEJ-ABC) in the diabetic condition were equivalent to those in the control group. In vivo fluorochrome labeling revealed increased MAR and bone remodeling in the diabetic mice. Further investigation found the diabetic mice had more osteoprogenitors recruited to the periodontium, allowing more bone formation to balance the enhanced bone resorption. STZ-induced T1DM mice, at an early stage, have elevated gingival inflammation and soft tissue degeneration and increased bone resorption; but still the alveolar bone was preserved by recruiting more osteoprogenitor cells and increasing the rate of bone formation. We conclude that inflammation and periodontitis precede alveolar bone deterioration in diabetes.

Vascular calcification in peritoneal dialysis patients and its association with bone-derived molecules and bone histomorphometry

IntroductionData regarding vascular calcification (VC) in contemporary peritoneal dialysis (PD) patients is scarce. Bone–vascular axis has been demonstrated in hemodialysis (HD). However, studies showing the link between bone disease and VC in PD patients are lacking. The role of sclerostin, dickkopf-related protein 1 (DKK-1), receptor activator for nuclear factor kB ligand and osteoprotegerin (OPG) in VC in PD remains to clarify. Materials and methodsBone biopsy was performed in 47 prevalent PD patients with histomorphometric analysis. Patients were submitted to pelvis and hands X-ray to evaluate VC using the Adragão score (AS). Relevant clinical and biochemical data was collected. ResultsThirteen patients (27.7%) had positive AS (AS≥1). Patients with VC were significantly older (58.9 vs. 50.4 years, p=0.011), had a lower dialysis dose (KT/V 2.0 vs. 2.4, p=0.025) and a higher glycosylated hemoglobin (7.2 vs. 5.4%, p=0.001). There was not any laboratorial parameter of mineral and bone disease used in clinical practice different between patients with or without VC. All diabetic patients had VC but only 8.1% of non-diabetic had VC (p<0.001). Patients with VC showed significantly higher erythrocyte sedimentation rate (ESR) (91.1 vs. 60.0mm/h, p=0.001), sclerostin (2250.0 vs. 1745.8pg/mL, p=0.035), DKK-1 (1451.6 vs. 1042.9pg/mL, p=0.041) and OPG levels (2904.9 vs. 1518.2pg/mL, p=0.002). On multivariate analysis, only ESR remained statistically significant (OR 1.07; 95% CI 1.01–1.14; p=0.022). Bone histomorphometric findings were not different in patients with VC. There was no correlation between bone formation rate and AS (r=−0.039; p=0.796). ConclusionThe presence of VC was not associated with bone turnover and volume evaluated by bone histomorphometry. Inflammation and diabetes seem to play a more relevant role in VC in PD.

Reduced bone formation and increased bone resorption drive bone loss in Eimeria infected broilers

Coccidiosis is an economically significant disease in the global poultry industry, but little is known about the mechanisms of bone defects caused by coccidiosis; thus, the study focused on effects of coccidiosis on the bone homeostasis of young broiler chickens. A total of 480 male Cobb500 broilers were randomly allocated into four treatment groups, including an uninfected control consuming diet ad libitum, two infected groups were orally gavaged with two different concentrations of sporulated Eimeria oocysts, and an uninfected pair-fed group fed the same amount of feed as the high Eimeria-infected group consumed. Growth performance and feed intake were recorded, and samples were collected on 6 days post infection. Results indicated that coccidiosis increased systemic oxidative status and elevated immune response in bone marrow, suppressing bone growth rate (P < 0.05) and increasing bone resorption (P < 0.05) which led to lower bone mineral density (P < 0.05) and mineral content (P < 0.05) under Eimeria infection. With the same amount of feed intake, the uninfected pair-fed group showed a distinguished bone formation rate and bone resorption level compared with the Eimeria infected groups. In conclusion, inflammatory immune response and oxidative stress in broilers after Eimeria infection were closely associated with altered bone homeostasis, highlighting the role of inflammation and oxidative stress in broiler bone homeostasis during coccidiosis.

Controlled released naringin-loaded liposome/sucrose acetate isobutyrate hybrid depot for osteogenesis in vitro and in vivo.

Introduction: A common problem in bone tissue engineering is that the burst release of active osteogenic factors is not beneficial for osteogenesis. This study aimed to prepare naringin (Ng) liposomes to reduce the burst release of Ng and improve new bone formation. Methods: We synthesized Ng liposomes using the thin-film hydration method. Drug-encapsulation efficacy experiments were conducted using the ultracentrifugation technique. The morphology and size distributions of freezedried liposomes were determined by transmission electron microscopy and dynamic light scattering. The Ng liposomes and Ng-lipo/sucrose acetate isobutyrate (SAIB) depots were characterized using Fourier transform infrared spectroscopy and in vitro release studies. After implantation of the Ng-lipo/SAIB depots, in vitro osteoblast-liposome interactions and in vivo osteogenesis were tested. Results: The formulation of freeze-dried Ng liposomes via an optimized recipe yielded nanosized (136.9 nm) negatively charged particles with a high encapsulation efficiency (~76.3%). Their chemical structure did not change after adding SAIB to the Ng liposomes. The burst release was reduced dramatically from 74.4% to 23.7%. In vivo, after 8 weeks, the new bone formation rate in the calvarial defects of Sprague-Dawley rats receiving Ng-lipo/SAIB was 57% compared with 25.18% in the control group (p = .0003). Discussion: Our results suggested that Ng-lipo/SAIB hybrid depots could serve as candidate materials for drug delivery in bone regeneration applications.

Abaloparatide Has the Same Catabolic Effects on Bones of Mice When Infused as PTH (1-34).

Abaloparatide is a peptide analog of parathyroid hormone-related protein (PTHrP 1-34) and was approved in 2017 as the second osteoanabolic peptide for treating osteoporosis. We previously showed that intermittent abaloparatide is equally as effective as PTH (1-34). This study was designed to compare the catabolic effects of PTH (1-34) and abaloparatide on bone in young female wild-type mice. Two-month-old C57Bl/6J female mice were continuously infused with human PTH (1-34) or abaloparatide at 80 μg/kg BW/day or vehicle for 2 weeks. At euthanasia, DEXA-PIXImus was performed to assess bone mineral density (BMD) in the whole body, femurs, tibiae, and vertebrae. Bone turnover marker levels were measured in sera, femurs were harvested for micro-computer tomography (μCT) analyses and histomorphometry, and tibiae were separated into cortical and trabecular fractions for gene expression analyses. Our results demonstrated that the infusion of abaloparatide resulted in a similar decrease in BMD as infused PTH (1-34) at all sites. μCT and histomorphometry analyses showed similar decreases in cortical bone thickness and BMD associated with an increase in bone turnover from the increased bone formation rate found by in vivo double labeling and serum P1NP and increased bone resorption as shown by osteoclast numbers and serum cross-linked C-telopeptide. Trabecular bone did not show major changes with either treatment. Osteoblastic gene expression analyses of trabecular and cortical bone revealed that infusion of PTH (1-34) or abaloparatide led to similar and different actions in genes of osteoblast differentiation and activity. As with intermittent and in vitro treatment, both infused PTH (1-34) and abaloparatide similarly regulated downstream genes of the PTHR1/SIK/HDAC4 pathway such as Sost and Mmp13 but differed for those of the PTHR1/SIK/CRTC pathway. Taken together, at the same dose, infused abaloparatide causes the same high bone turnover as infused PTH (1-34) with a net resorption in female wild-type mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Mesenchymal cell TRPM7 expression is required for bone formation via the regulation of chondrogenesis.

Transient receptor potential melastatin-subfamily member 7 (TRPM7) is a bifunctional protein containing a kinase fused to an ion channel permeated with cations, including Ca2+ and Mg2+. Trpm7-null mice show embryonic lethality. Paired related homeobox 1 (Prx1) is expressed in undifferentiated mesenchymal cells such as the progenitor cells of both chondrocytes and osteoblasts involved in limb skeleton formation. Prx1-Cre-dependent Trpm7 mesenchymal-deleted mice were generated to examine the role of TRPM7 in bone development. We found that Prx1-Cre;Trpm7fl/fl mice had shortened bones and impaired trabecular bone formation. Trabecular bone parameters, such as the bone volume (BV/TV), and trabecular number (Tb.N), were decreased in Prx1-Cre;Trpm7fl/fl mice. The cortical bone parameters of cortical bone area (Ct.Ar) and cortical bone thickness (Ct.Th) were also down-regulated in these mice. The bone formation rate in Prx1-Cre;Trpm7fl/fl mice was unchanged, but the hypertrophic area and cell size of the zone were smaller, and the expression of Col2a1, Col10a1 and Mmp13 was downregulated compared with control mice. These findings suggest impaired chondrogenesis in Prx1-Cre;Trpm7fl/fl mice compared to control mice. The receptor activator of nuclear factor-kappa B ligand (RANKL) expression was increased, and RANKL-positive cells and osteoclasts were markedly accumulated in the boundary region between the growth plate and trabecular bone. In contrast, TRPM7 KR mice, which are kinase-dead mutants in which the TRPM7 ion channel function has not been altered, showed no marked differences in trabecular or cortical bone parameters compared to wild-type mice. These findings suggest that TRPM7 is critical as a cation channel rather than as a kinase in bone development via the regulation of chondrogenesis.

Bioresorbable magnesium-based alloys containing strontium doped nanohydroxyapatite promotes bone healing in critical sized bone defect in rat femur shaft

Magnesium-based biomaterials have been in extensive research for orthopedic applications for decades due to their optimal mechanical features and osteopromotive nature; nevertheless, rapid degradation restricts their clinical applicability. In this study, pristine magnesium was purified (P-Mg) using a melt self-purification approach and reinforced using indigenously synthesized nanohydroxyapatite (HAP, 0.6 wt.%) and strontium substituted nanohydroxyapatite (SrHAP, 0.6 wt.%) using a low-cost stir assisted squeeze casting method to control their degradation rate. Using electron back-scattered diffraction (EBSD) and X-ray diffraction (XRD) examinations, all casted materials were carefully evaluated for microstructure and phase analysis. Mechanical characteristics, in vitro degradation, and in vitro biocompatibility with murine pre-osteoblasts were also tested on the fabricated alloys. For in vivo examination of bone formation, osteointegration, and degradation rate, the magnesium-based alloys were fabricated as small cylindrical pins with a diameter of 2.7 mm and a height of 2 mm. The pins were implanted in a critical-sized defect in a rat femur shaft (2.7 mm diameter and 2 mm depth) for 8 weeks and evaluated by micro-CT and histological evaluation for bone growth and osteointegration. When compared to P-Mg and P-MgHAP, micro-CT and histological analyses revealed that the P-MgSrHAP group had the highest bone formation towards the periphery of the implant and hence maximum osteointegration. When the removed pins from the bone defect were analyzed using GIXRD, they displayed hydroxyapatite peaks that were consistent with bio-integration. For P-Mg, P-MgHAP, and P-MgSrHAP 8 weeks after implantation , in vivo degradation rates derived from micro-CT were around 0.6 mm/year, 0.5 mm/year, and 0.1 mm/year, respectively. Finally, P-MgSrHAP possesses the requisite degradation rate as well as sufficient mechanical and biological properties, indicating that it has the potential to be used in the development/fabrication of biodegradable bioactive orthopaedic implants.

Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases

Systematic bone loss is commonly complicated with inflammatory bowel diseases (IBDs) with unclear pathogenesis and uncertain treatment. In experimental colitis mouse models established by dextran sulfate sodium and IL-10 knockout induced with piroxicam, bone mass and quality are significantly decreased. Colitis mice demonstrate a lower bone formation rate and fewer osteoblasts in femur. Bone marrow mesenchymal stem/stromal cells (BMSCs) from colitis mice tend to differentiate into adipocytes rather than osteoblasts. Serum from patients with IBD promotes adipogenesis of human BMSCs. RNA sequencing reveals that colitis downregulates Wnt signaling in BMSCs. For treatment, exosomes with Golgi glycoprotein 1 inserted could carry Wnt agonist 1 and accumulate in bone via intravenous administration. They could alleviate bone loss, promote bone formation, and accelerate fracture healing in colitis mice. Collectively, BMSC commitment in inflammatory microenvironment contributes to lower bone quantity and quality and could be rescued by redirecting differentiation toward osteoblasts through bone-targeted drug delivery.

Lack of Skeletal Effects in Mice with Targeted Disruptionof Prolyl Hydroxylase Domain 1 (Phd1) Gene Expressed in Chondrocytes.

The critical importance of hypoxia-inducible factor (HIF)s in the regulation of endochondral bone formation is now well established. HIF protein levels are closely regulated by the prolyl hydroxylase domain-containing protein (PHD) mediated ubiquitin-proteasomal degradation pathway. Of the three PHD family members expressed in bone, we previously showed that mice with conditional disruption of the Phd2 gene in chondrocytes led to a massive increase in the trabecular bone mass of the long bones. By contrast, loss of Phd3 expression in chondrocytes had no skeletal effects. To investigate the role of Phd1 expressed in chondrocytes on skeletal development, we conditionally disrupted the Phd1 gene in chondrocytes by crossing Phd1 floxed mice with Collagen 2α1-Cre mice for evaluation of a skeletal phenotype. At 12 weeks of age, neither body weight nor body length was significantly different in the Cre+; Phd1flox/flox conditional knockout (cKO) mice compared to Cre−; Phd1flox/flox wild-type (WT) control mice. Micro-CT measurements revealed significant gender differences in the trabecular bone volume adjusted for tissue volume at the secondary spongiosa of the femur and the tibia for both genotypes, but no genotype differences were found for any of the trabecular bone measurements of either femur or tibia. Similarly, cortical bone parameters were not affected in the Phd1 cKO mice compared to control mice. Histomorphometric analyses revealed no significant differences in bone area, bone formation rate or mineral apposition rate in the secondary spongiosa of femurs between cKO and WT control mice. Loss of Phd1 expression in chondrocytes did not affect the expression of markers of chondrocytes (collage 2, collagen 10) or osteoblasts (alkaline phosphatase, bone sialoprotein) in the bones of cKO mice. Based on these and our published data, we conclude that of the three PHD family members, only Phd2 expressed in chondrocytes regulates endochondral bone formation and development of peak bone mass in mice.

Could we use metallic wood for bone tissue engineering applications?

The principal purpose of tissue engineering is to stimulate the injured or unhealthy tissues to revive their primary function through the simultaneous use of chemical agents, cells, and biocompatible materials. One of the most recently used cellular materials is metallic wood, which possesses the strength of titanium as well as the density of natural materials, such as wood and water. Aside from its density, its cellular structure is also efficient, in which some parts are thick and dense, which hold the structure, and others are porous, which supports biological functions. This material has been predicted to be effective in bone tissue engineering in addition to several industrial applications as a result of its essential features, including its cellular structure, outstanding biocompatibility, mechanical performance, nanostructure lattice, high strength, corrosion resistance, and shape memory behavior. Thus, it is predicted that bone grafts made from metallic wood would have an acceptable rate of cell attachment, cell survival, vascularization, and new bone formation. The current review discusses the potential of utilizing metallic wood in bone tissue engineering applications, illustrating its coating and manufacturing capabilities.

Recent advances on bioactive baghdadite ceramic for bone tissue engineering applications: 20 years of research and innovation (a review).

Various artificial bone graft substitutes based on ceramics have been developed over the last 20 years. Among them, calcium-silicate-based ceramics, which are osteoconductive and can attach directly to biological organs, have received great attention for bone tissue engineering applications. However, the degradation rate of calcium-silicate and bone formation is often out of balance, resulting in stress shielding (osteopenia). A new strategy to improve the drawbacks of these ceramics is incorporating trace elements such as Zn, Mg, and Zr into their lattice structures, enhancing their physical and biological properties. Recently, baghdadite (Ca3ZrSi2O9) ceramic, one of the most appealing calcium-silicate-based ceramics, has demonstrated high bioactivity, biocompatibility, biodegradability, and cell interaction. Because of its physical, mechanical, and biological properties and ability to be shaped using various fabrication techniques, baghdadite has found high potential in various biomedical applications such as coatings, fillers, cement, scaffolds, and drug delivery systems. Undoubtedly, there is a high potential for this newly developed ceramic to contribute significantly to therapies to provide a tremendous clinical outcome. This review paper aims to summarize and discuss the most relevant studies performed on baghdadite-based ceramics and composites by focusing on their behavior in vivo and in vitro.

Osteoconductivity and neurotoxicity of silver-containing hydroxyapatite coating cage for spinal interbody fusion in rats.

The use of spinal instrumentation is an established risk factor for postoperative infection. To address this problem, we prepared silver-containing hydroxyapatite coating, consisting of highly osteoconductive hydroxyapatite interfused with silver. The technology has been adopted for total hip arthroplasty. Silver-containing hydroxyapatite coating has been reported to have good biocompatibility and low toxicity. However, no studies about applying this coating in spinal surgery have addressed the osteoconductivity and direct neurotoxicity to the spinal cord of silver-containing hydroxyapatite cages in spinal interbody fusion. In this study, we evaluated the osteoconductivity and neurotoxicity of silver-containing hydroxyapatite-coated implants in rats. Titanium (non-coated, hydroxyapatite-coated, and silver-containing hydroxyapatite-coated) interbody cages were inserted into the spine for anterior lumbar fusion. At 8 weeks postoperatively, micro-computed tomography and histology were performed to evaluate the osteoconductivity of the cage. Inclined plane test and toe pinch test were performed postoperatively to assess neurotoxicity. Micro-computed tomography data indicated no significant difference in bone volume/total volume among the three groups. Histologically, the hydroxyapatite-coated and silver-containing hydroxyapatite-coated groups showed significantly higher bone contact rate than that of the titanium group. In contrast, there was no significant difference in bone formation rate among the three groups. Data of inclined plane and toe pinch test showed no significant loss of motor and sensory function in the three groups. Furthermore, there was no degeneration, necrosis, or accumulation of silver in the spinal cord on histology. This study suggests that silver-hydroxyapatite-coated interbody cages produce good osteoconductivity and are not associated with direct neurotoxicity.

Sex-Specific Differences in Gsα-Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone.

Teriparatide, recombinant parathyroid hormone (PTH[1-34]), and abaloparatide, an analogue of PTH related-peptide (PTHrP[1-34]), are both anabolic medications for osteoporosis that target the PTH receptor PTH1R. PTH1R is a G protein-coupled receptor, and the stimulatory Gs protein is an important mediator of the anabolic actions of PTH1R activation in bone. We have published that mice lacking the α subunit of Gs in osteoprogenitors do not increase bone mass in response to PTH(1-34). Unexpectedly, however, PTH(1-34) still increases osteoblast numbers and bone formation rate in male mice, suggesting that PTH1R may have both Gs-dependent and -independent actions in bone. Here we examine the role of Gs signaling in the anabolic actions of abaloparatide. We find that abaloparatide increases bone formation in male mice with postnatal deletion of Gsα in Osx-expressing osteoprogenitors (P-GsαOsxKO mice) but not in female P-GsαOsxKO mice. Therefore, abaloparatide has anabolic effects on bone in male but not female mice that appear to be independent of Gs-mediated signaling. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Influence of mechanical stimuli and zoledronic acid on the femoral morfology in rats with obesity and limited mobility models

The aim. Investigate the long-term effect of WBV and bisphosphonate (zoledronic acid) on the morphological structure and mineral density of the rat femora. Materials and methods. Rats were divided into control and three experimental groups: I - experimental group - high-calorie diet + limited mobility (HCD + LM), II - experimental group - HCD + LM + whole body vibration (WBV 3 m/s2). III - experimental group - HCD + LM + administration of zoledronic acid (HCD + LM + Zol. at a dose of 0.025 mg / kg). Bone mineral density determination, scanning electron microscopy of trabecular meshwork and immunohistological examination were performed. Results. The application of the model of a high-calorie diet with limited mobility leads to the loss of the mineral component of trabeculae up to 16.2%. The trabecular layer thinned to 13.9% compared to the control group, and the intertrabecular spaces expanded. Under the influence of whole-body vibration, there was an increase in BMD in the femora compared to the group HCD + LM, and bone density remained at the control level until the 16th week of the experiment. In group III, the rate of bone formation increased, the ratio of bone to trabecular volume was significantly higher compared to the group HCD + LM. Starting from the 8th week, it increased by 8.1% and 13% at the end of the experiment, respectively.Conclusions. A high-calorie diet with limited mobility reduces the mineral density of the trabeculae in the femoral bone. Zoledronic acid effectively improves mineralization but leads to impairment of the morphology of the bone growth plate. The research results indicate that WBV can be an effective non-pharmacological method of maintaining bone health in young people.

Three-Dimensional Printed Polycaprolactone Mesh in Pediatric Cranial Vault Remodeling Surgery.

The surgical management of craniosynostosis has greatly evolved with improvements in both technology and understanding of the disease process. Some drawbacks remain regarding bone regeneration within the surgical bony gaps. Generally, bony gaps improve in the 12 to 24 months after surgery, but some gaps may remain for longer and cause deformity and/or require additional bony reconstruction. These considerations make tissue-engineered bone very attractive. Novel 3-dimensional printed bioresorbable mesh implants made of Polycaprolactone (PCL) can be used to fill the surgical bony defects. The authors seek to investigate how the use of a 3-dimensional printed biodegradable PCL mesh applied to bony defects in cranial vault surgery affects bone healing. Case series analysis of 8 pediatric patients who have undergone surgical intervention using PCL mesh implants for reconstruction of bony defects during craniosynostosis correction surgery. Radiological evaluation of 3 patients at random time points between 9 and 12 months postoperative revealed persistent bony gaps in areas where PCL mesh was laid. One patient who underwent a subsequent cranial vault surgery at 9 months was found to have less bone regeneration in the defect area where PCL mesh was used when compared with an adjacent area where a particulate bone graft was used. Based on our experience, the use of PCL mesh on its own did not augment bone regeneration. It is possible that a greater amount of time or increased vascularization of the scaffold is required, which supports the concept of regenerative matching axial vascularization or the further addition of osteogenic factors to increase the rate of bone formation.

Association of sex steroid hormones and new bone formation rate after iliac onlay grafting: a prospective clinical pilot study

PurposeThe present prospective study evaluates the association between new bone formation rate in the iliac onlay graft and sex steroid hormone serum levels.MethodsA total of 15 partially or completely edentulous postmenopausal females and 9 males with less than 5 mm height of the remaining alveolar bone underwent iliac onlay grafting followed by dental implant placement using a two-stage approach. Sex hormone binding globulin and 17β-estradiol serum levels were investigated by electrochemiluminescence immunoassay, while total testosterone level was analyzed using radioimmunoassay. At the time of implant placement, 12 weeks after grafting, bone biopsies were obtained and analyzed histomorphometrically. Statistical analysis was performed using linear mixed models.ResultsGrafting procedure was successfully performed in all patients. The mean new bone formation rate was 32.5% (116 samples). In men the mean new bone formation rate (38.1%) was significantly higher (p < 0.01) than in women (27.6%). Independent of gender 17β-estradiol and testosterone were positively associated to overall new bone formation rate, albeit a significant influence was only seen for 17β-estradiol in men (p = 0.020). Sex hormone binding globulin had no influence on new bone formation rate (p = 0.897). There was no significant association between new bone formation rate and age (p = 0.353) or new bone formation rate and body mass index (p = 0.248).ConclusionPositive association of 17ß-estradiol as well as testosterone with new bone formation rate after iliac onlay grafting indicates a role of sex steroid hormones in alveolar bone regeneration, although the observed influence was only significant for 17ß-estradiol in men.Graphical

ED-71 Prevents Glucocorticoid-Induced Osteoporosis by Regulating Osteoblast Differentiation via Notch and Wnt/β-Catenin Pathways.

Long-term glucocorticoid- usage can lead to glucocorticoid-induced osteoporosis (GIOP). The study focused on the preventative effects of a novel active vitamin D3 analog, eldecalcitol (ED-71), against GIOP and explored the underlying molecular mechanisms. Intraperitoneal injection of methylprednisolone (MPED) or dexamethasone (DEX) induced the GIOP model within C57BL/6 mice in vivo. Simultaneously, ED-71 was orally supplemented. Bone histological alterations, microstructure parameters, novel bone formation rates, and osteogenic factor changes were evaluated by hematoxylin-eosin (HE) staining, micro-computed tomography, calcein/tetracycline labeling, and immunohistochemical (IHC) staining. The osteogenic differentiation level and mineralization in pre-osteoblast MC3T3-E1 cells were evaluated in vitro using alkaline phosphatase (ALP) staining, alizarin red (AR) staining, quantitative polymerase chain reaction (qPCR), Western blotting, and immunofluorescence staining. ED-71 partially prevented bone mass reduction and microstructure parameter alterations among GIOP-induced mice. Moreover, ED-71 also promoted new bone formation and osteoblast activity while inhibiting osteoclasts. In vitro, ED-71 promoted osteogenic differentiation and mineralization in DEX-treated MC3T3-E1 cells and boosted the levels of osteogenic-related factors. Additionally, GSK3-β and β-catenin expression levels were elevated after ED-71 was added to cells and were accompanied by reduced Notch expression. The Wnt signaling inhibitor XAV939 and Notch overexpression reversed the ED-71 promotional effects toward osteogenic differentiation and mineralization. ED-71 prevented GIOP by enhancing osteogenic differentiation through Notch and Wnt/GSK-3β/β-catenin signaling. The results provide a novel translational direction for the clinical application of ED-71 against GIOP.

Inflammaging and Bone Loss in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) results in significant loss of sublesional bone, adding to the comorbidity of SCI with an increased risk of fracture and post-fracture complications. Unfortunately, the effect of SCI on skeletal health is also likely to rise, as the average age of SCI has increased and there are well-known negative effects of age on bone. To date, however, the impact of age and age-associated inflammation (inflammaging) on skeletal health after SCI remains largely unknown. To address this, we compared bone parameters in young (3 month) and middle-aged (9 month) male and female rats with a moderate thoracic contusion injury, to age- and sex-matched sham-operated controls. Skeletal parameters, locomotor function, and serum cytokine levels were assessed at both subchronic (30 days) and chronic (180 days) time points post-injury. We hypothesized that SCI would lead to a dramatic loss of bone immediately after injury in all SCI groups, with inflammaging leading to greater loss in middle-aged SCI rats. We also predicted that whereas younger rats might re-establish bone properties in more chronic phases of SCI, middle-aged rats would not. Supporting these hypothesis, trabecular bone volume was significantly lower in male and young female SCI rats early after injury. Contrary to our hypothesis, however, there was greater loss of trabecular bone volume, relative to age-matched shams, in young compared with middle-aged SCI rats, with no effects of SCI on trabecular bone volume in middle-aged female rats. Moreover, despite recovery of weight-supported locomotor activity, bone loss persisted into the chronic phase of injury for the young rats. Bone formation rates were lower in young male SCI rats, regardless of the time since injury, whereas both young and middle-aged female SCI rats had lower bone formation in the subchronic but not the chronic phase of SCI. In middle-aged rats, SCI-induced higher osteoclast surfaces, which also persisted into the chronic phase of SCI in middle-aged females. Neither age nor SCI-induced increases in inflammation seemed to be associated with bone loss. In fact, SCI had more dramatic and persistent effects on bone in male rats, whereas aging and SCI elevated serum cytokines only in female rats. Overall, this study demonstrates SCI-induced loss of bone and altered bone turnover in male and female rats that persists into the chronic phase post-injury. The sex- and age-dependent variations in bone turnover and serum cytokines, however, underscore the need to further explore both mechanisms and potential therapeutics in multiple demographics.