Bone Parameters Research Articles

Minimal Impact of Age on Adaptive Bone Formation in the Distal Tibia of US Army Basic Combat Trainees: The ARMI Study

ABSTRACT Introduction Although bone formation has been observed in the distal tibia of trainees during Basic Combat Training (BCT), some animal studies have demonstrated greater mechanosensitivity in the juvenile compared to the mature skeleton. How age affects skeletal adaptations to military training is unknown. The purpose of this study was to determine if skeletal adaptations to US Army BCT differ by age. Methods We enrolled 2085 trainees (1303 males, 782 females). High-resolution peripheral quantitative computed tomography was used to assess total, cortical, and trabecular bone mineral density (BMD) and the microarchitecture of the distal tibia before and after 8 wk of BCT. Generalized linear models were used to compare mean percent change (95% confidence interval (CI)) in each bone parameter by age group (<20, 20–25, 26–29, and ≥30 yr) and to evaluate differences in bone parameter changes between age groups (effect estimates (95% CI)). Models were stratified by sex with multivariable adjustment. Results Male and female trainees in all age groups had increases in total BMD, trabecular BMD, and trabecular bone volume fraction from baseline (P < 0.01 for all). Male and female trainees also had increases in trabecular thickness from baseline in all groups (P < 0.05) except females ≥30 yr old. Female trainees 20–25 yr old had a significantly larger increase in trabecular thickness than those <20 yr old (effect estimate (95% CI), 0.33% (0.02%–0.64%); P < 0.05). Trabecular microarchitecture was largely not otherwise different between age groups for either sex. Male and female trainees <20 yr old had greater changes in cortical BMD compared to older age groups (males, P < 0.01; females, P < 0.05 for all). Conclusion Trainees <20 yr old experience the greatest improvements in cortical BMD at the distal tibia during US Army BCT, suggesting that adaptive bone formation in cortical bone may be attenuated with skeletal maturity. However, the mechanosensitivity of trabecular bone to exercise training remains intact regardless of age.

Determinants of bone mineral density in various regions of the skeleton among smokers and non-smokers: the role of physical activity.

The adult human skeleton is composed of cortical and cancellous bone. The proportions of these two types of bone tissue differ in various parts of the skeleton. The aim of this cross-sectional study was to quantify the determinants of bone mineral density (BMD) and bone mineral content in various regions of interest (ROIs) in smokers and never-smokers. In this study, 4,332 bone scans of three regions of interest (ROIs) were analyzed: the forearm (distal and proximal), femur, and lumbar spine. Body composition and bone parameters were measured using dual-energy X-ray absorptiometry. Smoking was measured using the Global Adult Tobacco Survey questionnaire. Body mass index (BMI) was calculated, and physical activity (PA) was characterized by the metabolic equivalent of task (MET). Among women, the interaction between PA (positive β coefficient) and smoking (negative β coefficient) was a significant predictor of BMD in the distal and proximal forearm (adj. R2 = 0.40 and R2 = 0.58; p < 0.001). The interaction of three variables-age, smoking (negative β), and MET (positive β)-was significant for total hip BMD (adj. R2 = 0.54; p < 0.001). The interaction between BMI and MET (positive β) and smoking (negative β) was significant for BMD in the lumbar spine (adj. R2 = 0.62; p < 0.001). In men, the interaction between MET (positive β) and smoking (negative β) was significant for BMD in the forearm and lumbar spine (adj. R2 = 0.44, R2 = 0.46, and R2 = 0.49; p < 0.01). Smoking alone was a significant negative predictor of total hip BMD (adj. R2 = 0.34; p < 0.001). Among both women and men, never-smokers had significantly better bone parameters than smokers. Smoking was a significant negative predictor for BMD in the various ROIs in both women and men. Physical activity was a significant positive predictor of BMD, with a strong association with bone parameters.

Effect of bisphosphonate on bone microstructure, mechanical strength in osteoporotic rats by ovariectomy

BackgroundBisphosphonate (BP) can treat osteoporosis and prevent osteoporotic fractures in clinical. However, the effect of BP on microstructure and mechanical properties of cortical and trabecular bone has been taken little attention, separately.MethodsIn this study, BP was used to intervene in ovariectomized female SD rats. The femoral micro-CT images were used to measure the structural parameters and reconstruct the 3D models in volume of interest. The structural parameters of cortical and trabecular bone were measured, and the mechanical properties were predicted using micro-finite element analysis.ResultsThere was almost no significant difference in the morphological structure parameters and mechanical properties of cortical bone between normal, ovariectomized (sham-OVX) and BP intervention groups. However, BP could significantly improve bone volume fraction (BV/TV) and trabecular separation (Tb.SP) in inter-femoral condyles (IT) (sham-OVX vs. BP, p < 0.001), and had no significant effect on BV/TV in medial and lateral femoral condyles (MT, LT). Similarly, BPs could significantly affect the effective modulus in IT (sham-OVX vs. BP, p < 0.001), and had no significant difference in MT and LT. In addition, the structural parameters and effective modulus showed a good linear correlation.ConclusionIn a short time, the effects of BP intervention and osteoporosis on cortical bone were not obvious. The effects of BP on trabecular bone in non-main weight-bearing area (IT) were valuable, while for osteoporosis, the main weight-bearing area (MT, LT) may improve the structural quality and mechanical strength of trabecular bone through exercise compensation.

Angular Trajectory of the Vestibular Aqueduct in a Cohort of Chinese Patients with Unilateral Ménière's Disease: Association with Other Imaging Indices and Clinical Profiles.

We aimed to investigate the association between the angular trajectory of the vestibular aqueduct (ATVA) with other radiological parameters of temporal bone and clinical characteristics in patients with Ménière's disease (MD). A total of 125 unilateral MD patients and 118 controls were enrolled. Computer tomography (CT)-based radiological parameters included ATVA, vestibular aqueduct (VA) visibility, VA morphology, the vertical part of the posterior semicircular canal-the posterior fossa distance (PPD), and peri-VA pneumatization. The clinical characteristics of MD patients included gender, age of diagnosis/onset, disease duration, migraine history, clinical staging, and the results of audio-vestibular tests. The radiological parameters and clinical characteristics in MD patients were compared. Compared with control ears, ATVA ≥ 140° was more prevalent and ATVA ≤ 120° was less frequent in the MD-affected side. For the MD-affected side, MD patients with ATVA ≥ 140° exhibited more severe VA invisibility and obliteration and higher male preponderance than those with ATVA ≤ 120°. Other radio-clinical features did not differ between these two subgroups. In the current study, ATVA ≥ 140°, an indicator of a hypoplastic endolymphatic sac, was found in approximately one-third of the affected and unaffected ears of patients with MD, as well as in a minority of controls. This suggests that the indices may be a predisposing factor rather than a specific marker for the MD ear. The male preponderance in MD patients with hypoplastic ES suggests a gender difference in the anatomical factors for MD pathogenesis.

A numerical simulation method for ultrasonic transmission in cancellous bone based on a four-parameter random growth method

Abstract Quantitative ultrasound (QUS) has been widely used in non-destructive evaluation of bone health in research and clinical practice. To make a more accurate bone evaluation, the transmission characteristics of ultrasound in the bone need to be understood in detail. In the two-dimensional finite element model, cancellous bone is usually simulated by a non-porous structure solid or by approximating bone trabeculae as ellipses, which is different from real bone. However, although the error of the model constructed by bone CT images is small, it needs to be based on real bone samples, and the samples are limited. Therefore, a modeling method of cancellous bone based on four-parameter random growth method was proposed in this paper, and on this basis, numerical simulation of ultrasonic transmission was carried out. Firstly, based on the four-parameter random growth method, the aggregation algorithm is used to concentrate discrete pixels and smooth the edge of pores. Meanwhile, the built-in algorithm ensures the same porosity before and after processing to reduce the discrete pore structure. Secondly, based on COMSOL to establish the simulation model of ultrasonic propagation in cancellous bone, we analyzed the change of acoustic field distribution, discussed the correlation between the porosity of cancellous bone and backscattering coefficient (BSC) based on the ultrasonic backscattering method, and compared the experimental results of CT scan images of bone samples. The experimental results show that the cancellous bone modeling method in this paper has the same conclusion as the method based on CT images, which verifies the feasibility of this method. This method can generate a geometric model of the cancellous bone microstructure with specified porosity and different bone trabecular distribution, which is similar to the real bone structure, and can be directly imported into the finite element software to facilitate the study of bone microstructure related problems. It provides a more convenient method to study the mechanism of ultrasonic propagation in cancellous bone and has important significance in solving the inverse problem of recovering effective bone parameters from the received ultrasonic signals.

Calcium-Phosphorus Metabolism in Females with Autoimmune Thyroiditis and Hypothyroidism

Thyroid dysfunction is frequently associated with disturbances of calcium and phosphorus homeostasis. Previous studies on bone and mineral metabolism in women with autoimmune thyroiditis (AIT) and hypothyroidism have conflicting results. The aim of the present work was to study the parameters of calcium-phosphorus metabolism in women with newly diagnosed autoimmune hypothyroidism and to compare them with those of the control group of healthy women. The study included 64 women with newly diagnosed autoimmune hypothyroidism. A comparison was made with the data of 75 age-, BMI- and menopausal state-matched healthy women. FT3, FT4, TSH, TPO-Ab, TG-Ab, total and ionized serum calcium, inorganic phosphate, magnesium, parathyroid hormone (PTH) and 25(OH) vitamin D were studied. Total and ionized calcium were lower in hypothyroid women in the absence of statistically significant difference compared to the controls. Intergroup analysis revealed no differences in serum phosphorus and 25(OH)D levels. Serum magnesium and PTH were significantly higher in hypothyroid group. These results coincide with some of the studies that examine the parameters of bone and mineral metabolism in hypothyroidism. Bone turnover is suppressed due to impaired mobilization of calcium from the bone, leading to decreased serum calcium levels and elevated PTH. We found a significant effect of thyroid hormones on magnesium homeostasis. The study did not find differences in vitamin D status between the groups. The observed inverse correlation between 25(OH)D and TgAb supports the concept of pathogenic relationship between vitamin D and the development of AIT.

Bone Quality Indices Correlate with Growth Hormone Secretory Capacity in Women Affected by Weight Excess: A Cross-Sectional Study.

Background/Objectives: Obesity can be associated with impaired growth hormone (GH) secretion, with possible negative repercussions on bone health. We aimed to investigate the relationships between GH secretory capacity, evaluated with GHRH + arginine stimulation test, and bone parameters, assessed with a dual-energy X-ray absorptiometer, in a population of adult female patients affected by overweight and obesity. Methods: We assessed 276 women affected by overweight or obesity referred to the High-Specialization Center for the Care of Obesity, Umberto I Polyclinic, between 2014 and 2019 with signs or symptoms of growth hormone deficiency (GHD). Results: A total of 97 patients were diagnosed with GHD, and 179 patients with normal GH secretion were considered our control group. GHD patients showed a significantly reduced trabecular bone score (TBS) (p = 0.01). Bone quality parameters corrected for body mass index (BMI) had a positive and significant linear correlation with stimulated GH secretory capacity. Conclusions: In conclusion, bone quality, evaluated by TBS and hip structural analysis, correlates with GH-stimulated secretory capacity. GHD may act as an additive factor in the alteration of bone microarchitecture in patients affected by obesity, who are already at a higher risk of fractures.

METTL14-mediated HOXA5 m6A modification alleviates osteoporosis via promoting WNK1 transcription to suppress NLRP3-dependent macrophage pyroptosis

BackgroundOsteoporosis is a commonly diagnosed metabolic bone disease. NLRP3 inflammasome activation and pyroptosis are observed during osteoporosis. However, the mechanism by which NLRP3-mediated pyroptosis contributes to osteoporosis remains largely undefined. MethodsOvariectomized (OVX) mice were employed as an in vivo model of osteoclastogenesis. H&E staining and micro-CT detected the histological changes and bone parameters in the femur tissues. RANKL-treated macrophages were used as the in vitro model of osteoclastogenesis, and LPS/ATP treatment was used as the macrophage pyroptosis model. The cytotoxicity, cytokine secretion and caspase-1 activity were assessed by LDH release assay, ELISA and flow cytometry, respectively. The osteoclast formation ability was detected by TRAP staining. qRT-PCR, IHC and Western blotting detected the expression and localization of METTL14, pyroptosis-related or osteoclast-specific molecules in femur tissues or macrophages. Mechanistically, MeRIP assessed the m6A modification of HOXA5. Luciferase and ChIP assays were employed to detect the direct association between HOXA5 and WNK1 promoter in macrophages. ResultsMETTL14, HOXA5 and WNK1 were decreased in OVX mice, which was associated with pyroptosis. METTL14 or HOXA5 overexpression suppressed macrophage-osteoclast differentiation and pyroptosis, along with the upregulation of WNK1. METTL14-mediated m6A modification stabilized HOXA5 mRNA and increased its expression, and HOXA5 regulated WNK1 expression via direct binding to its promoter. Functional studies showed that WNK1 knockdown counteracted METTL14- or HOXA5-suppressed pyroptosis and macrophage-osteoclast differentiation. In OVX mice, overexpression of METTL14 or HOXA5 alleviated osteoporosis via suppressing WNK1-dependent NLRP3 signaling. ConclusionMETTL14-mediated HOXA5 m6A modification increased its expression, thereby inducing WNK1 expression and suppressing NLRP3-dependent pyroptosis to alleviate osteoporosis. The combination of METTL14 or HOXA5 agonist with pyroptosis targeted therapy may be a promising therapeutic approach for osteoporosis. The Translational Potential of this Article·•METTL14 or HOXA5 overexpression suppressed macrophage-osteoclast differentiation and pyroptosis in macrophages.·•METTL14-mediated m6A modification stabilized HOXA5 mRNA and increased its expression.•HOXA5 regulated WNK1 expression via direct binding to its promoter.•Silencing of WNK1 reversed METTL14- or HOXA5-suppressed pyroptosis and macrophageosteoclast differentiation.·•METTL14 or HOXA5 overexpression alleviated osteoporosis via suppressing WNK1-dependent NLRP3 signaling in OVX mice.

Anti-inflammatory, antiosteoporotic, and bone protective effect of hydroxysafflor yellow A against glucocorticoid-induced osteoporosis in rats.

Osteoporosis is a common condition worldwide, affecting millions of people. Women are more commonly affected than men, and the risk increases with age. Inflammatory reaction plays a crucial role in the expansion of osteoporosis. Osteoporosis is characterized by a gradual decline in bone density and bone tissue quality, which increases fragility and raises the risk of fractures. We scrutinized the anti-osteoporosis effect of hydroxysafflor yellow A (HYA) against glucocorticoid-induced osteoporosis (GIOP) in rats. In-silico study was carried out on EGFR receptor (PDBID: 1m17), Estrogen Alpha (PDB id: 2IOG), MTOR (PDB id: 4FA6), RANKL (PDB id: 1S55), and VEGFR2 (PDB id: 1YWN) protein. For this investigation, Sprague-Dawley (SD) rats were used, and they received an oral dose of HYA (5, 10, and 20 mg/kg, b.w.) along with a subcutaneous injection of dexamethasone (0.1 mg/kg/day) to induce osteoporosis. The biomechanical, bone parameters, antioxidant, cytokines, inflammatory, nutrients, hormones, and urine parameters were estimated. HYA treatment significantly suppressed the body weight and altered the organ weight. HYA treatment remarkably suppressed the level of alkaline phosphatase, acid phosphatase, and improved the level of bone mineral density (total, proximal, mild, and dis). HYA treatment restored the level of calcium (Ca), phosphorus (P), estradiol (E2), and parathyroid hormone near to the normal level. HYA treatment remarkably altered the level of biomechanical parameters, antioxidant, cytokines, urine, and inflammatory parameters. HYA treatment altered the level of osteoprotegerin (OPG), receptor activator of nuclear factor kappa beta (RANKL) and RANKL/OPG ratio. The result clearly showed the anti-osteoporosis effect of HYA against GIOP-induced osteoporosis in rats via alteration of antioxidant, cytokines, inflammatory, and bone protective parameters.

Conventional steroids vs. dual-release hydrocortisone on metabolic, cardiovascular and bone outcomes in adrenal insufficiency: a 10-year study.

Adrenal insufficiency (AI) is characterized by increased mortality compared to general population, mainly due to cardiovascular disease. Conventional glucocorticoid (GC) replacement therapy has a role in determining the increased mortality risk. Primary outcome of the current study was to evaluate the impact of 10 years of conventional GCs and DR-HC on body weight changes in treatment-naïve patients with AI. Secondary outcomes were changes from baseline to 5 and 10 years in anthropometric and metabolic profile, insulin sensitivity, cardiovascular and bone parameters. We prospectively randomised 42 patients to conventional GCs (cortisone acetate or hydrocortisone) and 44 to DR-HC (1:1). Anthropometric, metabolic, cardiovascular and bone parameters were evaluated at baseline and after 5 and 10 years of follow-up. This trial is registered at ClinicalTrials.gov NCT06260462. At 10 years of follow-up, patients with conventional GCs had significantly higher values ​​of BMI (p=0.031), waist circumference (p=0.047), systolic blood pressure (p=0.039), total and LDL cholesterol (p=0.041 and p=0.042), HbA1c (p=0.040), HOMA-IR (p=0.006), AUC2h of glucose (p<0.001), thickness of the interventricular septum in diastole and of the posterior wall (both p<0.001) and significantly lower values ​​of oral disposition index (p=0.001) and ISI-Matsuda (p<0.001), lumbar spine T score (p=0.036) and femoral neck Z score (p=0.026), compared to patients treated with DR-HC. In patients with treatment-naïve AI, 10 years of conventional GC treatment is associated with a worsening of metabolic, insulin-sensitivity, cardiac and bone outcomes, while DR-HC had no impact on them achieving a lower risk of developing comorbidities.

Somatic Structure and Ultrasound Parameters of the Calcaneus Bone in Combat Sports Athletes in Relation to Vitamin D3 Levels.

Background/Objectives: Physical activity is widely recognized for its beneficial effects on bone density during adolescence, which could lead to enhanced bone density in later life, thus acting as a health-promoting activity with long-lasting implications. However, not all studies are conclusive regarding the type, intensity, duration, and frequency of the most effective physical activities. This study focuses on combat sports athletes and examines the relationship between their somatic build and heel bone parameters using ultrasound (USG) and their vitamin D3 levels. Methods: The study included 40 male athletes specializing in various combat sports. The measurements of body height, body mass, skinfold thickness, and bone widths at multiple sites were performed to estimate the somatic build. The USG parameters of the heel bone and the blood levels of vitamin D3 were also recorded. Statistical significance was determined using one-way ANOVA, with differences among sports disciplines also examined. Results: The study found significant differences in the body composition and USG bone parameters among athletes from different combat sports (p ≤ 0.05). The calcaneus stiffness index (SI) and speed of sound (SOS) were significantly higher in athletes with normal vitamin D3 levels compared to those with below-normal levels (p = 0.0015 and p = 0.001, respectively). These findings suggest that vitamin D3 may influence bone stiffness and density. Conclusions: The study underscores the importance of maintaining adequate vitamin D3 levels to support bone mineralization in athletes, particularly those training indoors with limited exposure to sunlight. It also highlights the potential of using USG as a non-invasive method to assess bone health, aiding in the optimization of training programs to prevent injuries and improve performance.

Fibronectin isoforms promote postnatal skeletal development

Fibronectin (FN) is a ubiquitous extracellular matrix glycoprotein essential for the development of various tissues. Mutations in FN cause a unique form of spondylometaphyseal dysplasia, emphasizing its importance in cartilage and bone development. However, the relevance and functional role of FN during skeletal development has remained elusive. To address these aspects, we have generated conditional knockout mouse models targeting the cellular FN isoform in cartilage (cFNKO), the plasma FN isoform in hepatocytes (pFNKO), and both isoforms together in a double knockout (FNdKO). We used these mice to determine the relevance of the two principal FN isoforms in skeletal development from postnatal day one to the adult stage at two months.We identified a distinct topological FN deposition pattern in the mouse limb during different gestational and postnatal skeletal development phases, with prominent levels at the resting and hypertrophic chondrocyte zones and in the trabecular bone. Cartilage-specific cFN emerged as the predominant isoform in the growth plate, whereas circulating pFN remained excluded from the growth plate and confined to the primary and secondary ossification centers. Deleting either isoform independently (cFNKO or pFNKO) yielded only relatively subtle changes in the analyzed skeletal parameters. However, the double knockout of cFN in the growth plate and pFN in the circulation of the FNdKO mice significantly reduced postnatal body weight, body length, and bone length. Micro-CT analysis of the adult bone microarchitecture in FNdKO mice exposed substantial reductions in trabecular bone parameters and bone mineral density. The mice also showed elevated bone marrow adiposity. Analysis of chondrogenesis in FNdKO mice demonstrated changes in the resting, proliferating and hypertrophic growth plate zones, consistent alterations in chondrogenic markers such as collagen type II and X, decreased apoptosis of hypertrophic chondrocytes, and downregulation of bone formation markers. Transforming growth factor-β1 and downstream phospho-AKT levels were significantly lower in the FNdKO than in the control mice, revealing a crucial FN-mediated regulatory pathway in chondrogenesis and bone formation.In conclusion, the data demonstrate that FN is essential for chondrogenesis and bone development. Even though cFN and pFN act in different regions of the bone, both FN isoforms are required for the regulation of chondrogenesis, cartilage maturation, trabecular bone formation, and overall skeletal growth.

High-fiber diet reduces bone formation but does not affect bone microarchitecture in type 2 diabetes individuals.

Bone fragility is a recognized complication of type 2 diabetes mellitus (T2DM), increasing patient morbidity. Thus, the development of an effective intervention to prevent diabetic bone fragility is urgently needed. As lifestyle intervention represents an effective option for diabetes management, it may have an impact on bone health. While studies have shown a beneficial effect of dietary fiber in T2DM management, its effect on bone health is still unclear. Thus, we investigated the impact of a high-fiber diet on bone and glucose control in men and women with T2DM. Forty-five T2DM patients (HbA1c: 6.5% ± 0.49%, age: 74 ± 7.29yr) scheduled for hip arthroplasty were randomly assigned to follow a high-fiber diet (38g/day) or to make no diet changes for 12wk. Interestingly, BMI decreased by 4% (p <.0001) and HbA1c by 3.4% (p <.0001) in the high-fiber diet group, but did not decrease in the control group. However, serum concentration of the bone formation marker procollagen type 1 amino-terminal propeptide (P1NP) decreased by 8.6 % in the high-fiber diet group (p =.0004), whereas it remained unchanged in the control group. In contrast, similar to the control group, serum concentration of the bone resorption marker C-terminal telopeptide of type I collagen (CTX) concentrations did not change in the high-fiber diet group. Bone microCT analysis revealed no changes in trabecular and cortical bone parameters between the high-fiber diet and control groups. Similarly, real-time (RT)-PCR analysis in bone tissue showed no changes in the gene expression of Wnt pathway-related genes (Sost, Dkk-1, Wnt10b, and Lef-1), bone formation markers (Runx2, Col1a1, and Ocn), and inflammatory cytokines (IL-6, IL-8, TNF-α, and IL-10) between the two groups. Our findings suggest that 12-wk high-fiber diet intervention improves metabolic outcomes in patients with T2DM. However, it may reduce bone formation without affecting bone microarchitecture or Wnt pathway regulation.

Effects of Two Types of Resistance Training Modalities (Hypertrophy vs. Contrast Training) on Bone Parameters in a Group of Healthy Elderly Women

The aim of the present study was to explore the effects of two types of resistance training modalities (hypertrophy training vs. contrast training) on bone health parameters in a group of healthy elderly women. Forty-nine healthy elderly women whose ages range between 60 and 70 years were included in this study. The study population was randomly divided into three groups: hypertrophy training group (HTG; n=16), contrast training group (CTG; n=16) and control group (CG; n=17). Bone mineral density (BMD) values at the whole body (WB), lumbar spine (L1-L4), total hip (TH) and femoral neck (FN) were measured by DXA before and after 12 months of resistance training. Composite indices of femoral neck strength were calculated. WB BMD, L1-L4 BMD, TH BMD and FN BMD increased in the contrast training group. WB BMD and L1-L4 BMD increased in the hypertrophy training group, while TH BMD and FN BMD remained unchanged. Significant decreases in WB BMD, L1-L4 BMD, TH BMD and FN BMD were observed in the control group. The contrast training group showed the highest improvements in BMD values compared to the two other groups. Both experimental groups (HTG and CTG) showed similar significant improvements in composite indices of femoral neck strength and muscular strength. In conclusion, contrast training and hypertrophy training can stimulate bone gain at clinically important sites of osteoporotic fractures in elderly women.

Phytase super-dosing modulates bone parameters and the concentration of the calcium epithelial carrier calbindin-D28k in quails (Coturnix coturnix japonica) under thermal stress

Context Thermal stress causes significant changes in the bioavailability of minerals, especially calcium, in laying birds, resulting in reduced egg production, and compromising egg quality. Therefore, it is necessary to use additives that provide better nutrient availability and minimise the negative effects caused by high temperatures. Aims This study aimed to evaluate the effects of super-dosing the diet of laying quails submitted to different temperatures with phytase on their bone parameters and on the epithelial calcium transporter calbindin-D28K positivity. Methods Seven hundred and twenty (720) Japanese quails in the production phase were distributed in a completely randomised design, in a 5 × 3 factorial design, with five supplementation levels of phytase (0, 500, 1000, 1500, and 3000 FTU/kg), and three temperatures (24°C, 30°C and 36°C), totalling 15 treatments, and six replications of eight birds each. The study began at the 8th week of age and continued for two cycles of 21 days, totalling 42 days of experiment. Bone parameters of the tibias and calbindin-D28K positivity were measured by immunohistochemistry. The data were submitted to variance, Tukey, and regression analyses. Key results At 24°C, birds had higher averages for proximal, medial, and distal diaphyses than did birds at 30°C and 36°C, and a greater breaking strength of the tibias than did those at 36°C. There was an increasing linear effect on the medial diaphysis and Seedor index in the tibias with an increasing phytase supplementation level. Calcium (Ca) in the tibias was higher in birds kept at 30°C at a supplementation level of up to 1000 FTU of phytase, than in the birds at 24°C and 36°C, equalling at 1500 FTU, and lower at 3000 FTU. There was a quadratic effect for phosphorus (P) and the Ca:P ratio in the tibias of quails submitted to increasing concentrations of phytase. Quails kept at 30°C showed greater anti-calbindin-D28K positivity in the duodenum and jejunum, when compared to animals subjected to temperatures of 24°C and 36°C. Phytase doses of 500 and 1000 FTU increased calbindin-D28K positivity in the duodenum of quails kept at 30°C. At a supplementation level of 1500 FTU, phytase provided greater eggshell thickness and greater calbindin-D28K positivity in the uterus of quails kept at 36°C. Conclusions Therefore, it is recommended to use 1500 FTU of phytase for Japanese quail exposed to high temperatures. Implications These findings suggest that dietary phytase super-dosing can help alleviate thermal stress in Japanese quail.

Clinical and Micro-CT analyses of Vertical Guided Bone Regeneration of Mandible using a d-PTFE Membrane, Autogenous Bone, and High-Temperature Processed Xenograft- A Case Series Study.

Purpose: To evaluate the efficacy of vertical guided bone regeneration (GBR) in the mandible utilizing a non-resorbable membrane and a bone graft combination of autogenous bone chips, and high-temperature processed (HTP) xenograft, through CT scans and microCT analysis. Materials and Methods: Patients underwent vertical ridge augmentation procedures prior to implant placement. The surgical procedure included flap elevation and placement of a bone graft comprising a 1:1 combination of autogenous posterior mandible-derived bone chips, and HTP xenograft graft particles covered with a d-PTFE membrane trimmed to suit the 3D shape of the bone defect. This was fastened securely with titanium screws and pins, and a layer of native collagen membrane. Post-operative complications and ridge measurements were assessed. Pre bone augmentation and pre implant placement bone parameters were obtained from CT scans. Biopsy specimens collected during implantation were examined by microCT. Results: All 13 study procedures were successful without any complications. The results revealed average vertical and horizontal bone gains of 3.35 mm and 5.15 mm respectively. A total of 33 implants were successfully placed in the augmented areas, without the need for further bone augmentation. MicroCT analysis revealed 48% bone, 15% filler material, and 37% non-calcified tissue in the augmented region compared to 65% bone, 3% filler material, and 32% non-calcified tissue in the pristine bone. Conclusions: A mixture of autogenous bone and HTP xenograft, covered with a d-PTFE membrane and a layer of native collagen membrane is effective for vertical GBR.

Assessment of the bony resection margin distance in bone-invasive oral cancer using laser-induced breakdown spectroscopy

ObjectivesInadequate resection margins of less than 5 mm impair local tumor control. This weak point in oncological safety is exacerbated in bone-infiltrating tumors because rapid bone analysis procedures do not exist. This study aims to assess the bony resection margin status of bone-invasive oral cancer using laser-induced breakdown spectroscopy (LIBS).Materials and methodsLIBS experiments were performed on natively lasered, tumor-infiltrated mandibular cross-sections from 10 patients. In total, 5,336 spectra were recorded at defined distances from the tumor border. Resection margins < 1 mm were defined as very close, from 1–5 mm as close, and > 5 mm as clear. The spectra were histologically validated. Based on the LIBS spectra, the discriminatory power of potassium (K) and soluble calcium (Ca) between bone-infiltrating tumor tissue and very close, close, and clear resection margins was determined.ResultsLIBS-derived electrolyte emission values of K and soluble Ca as well as histological parameters for bone neogenesis/fibrosis and lymphocyte/macrophage infiltrates differ significantly between bone-infiltrating tumor tissue spectra and healthy bone spectra from very close, close, and clear resection margins (p < 0.0001). Using LIBS, the transition from very close resection margins to bone-infiltrating tumor tissue can be determined with a sensitivity of 95.0%, and the transition from clear to close resection margins can be determined with a sensitivity of 85.3%.ConclusionsLIBS can reliably determine the boundary of bone-infiltrating tumors and might provide an orientation for determining a clear resection margin.Clinical relevanceLIBS could facilitate intraoperative decision-making and avoid inadequate resection margins in bone-invasive oral cancer.

Fibroblast growth-factor 23-Klotho axis is associated with systemic inflammation and myokine profile in children with chronic kidney disease.

Chronic kidney disease is linked to a disturbed fibroblast growth factor-23 (FGF23)-Klotho axis and an imbalance between myostatin and insulin-like growth factor-1 (IGF-1) expression. This cross-sectional study investigates the association of the FGF23-Klotho axis and myokine profile with serum interleukin-6 (IL-6) and their interactions in pediatric patients. Serum calcium, phosphorus, 25-hydroxyvitamin D, parathormone, c-terminal FGF23, a-Klotho, myostatin, follistatin, IGF-1, and IL-6 were measured in 53 patients with GFR < 60ml/min/1,73m2. Myostatin to lean mass (LM) and to IGF-1 ratios were calculated. IL-6 level > 3rd quartile was considered as high. Myostatin, IGF-1, and follistatin were correlated to LM (rs = 0.513, p < 0.001, rs = 0.652, p < 0.001, rs=-0.483, p < 0.001). Myostatin and follistatin were correlated to IGF-1 (rs = 0.340, p = 0.014, rs=-0.385, p = 0.005). Myostatin/LM but not myostatin or myostatin/IGF-1 ratio was significantly higher in CKD 5D patients (p = 0.001,p = 0.844, p = 0.111). Among mineral bone parameters, lnFGF23 was correlated to lnIL-6 (rs = 0.397, p = 0.004) and associated with high IL-6 (OR 1.905, 95% CI 1.023-3.548). Among myokines, myostatin/IGF-1 ratio was correlated to lnIL-6 (rs = 0.395, p = 0.004) and associated with high IL-6 (OR 1.113, 95% CI 1.028-1.205). All associations were adjusted to CKD stage. Myostatin was correlated to lnFGF23 (rs = 0.331, p = 0.025) and myostatin/IGF-1 ratio to lnKlotho (rs=-0.363, p = 0.013), after adjustment for CKD stage, lnIL-6 and other mineral bone parameters. In pediatric CKD, FGF23 and myostatin/IGF-1 ratio are associated with IL-6, indicating a link between systemic inflammation, mineral bone, and myokine disorders. The correlations between myostatin and FGF23 and between myostatin/IGF-1 and Klotho suggest an interaction between mineral bone and muscle metabolism.

Development of a continuum-based, meshless, finite element modeling approach for representation of trabecular bone indentation

Implant subsidence into the underlying trabecular bone is a common problem in orthopaedic surgeries; however, the ability to pre-operatively predict implant subsidence remains limited. Current state-of-the-art computational models for predicting subsidence have issues addressing this clinical problem, often resulting from the size and complexity of existing subject-specific, image-based finite element (FE) models. The current study aimed to develop a simplified approach to FE modeling of subject-specific trabecular bone indentation resulting from implant penetration.Confined indentation experiments of human trabecular bone with flat- and sharp-tip indenters were simulated using FE analysis. A generalized continuum-level approach using a meshless smoothed particle hydrodynamics (SPH) approach and an isotropic crushable foam (CF) material model was developed for the trabecular bone specimens. Five FE models were generated with CF material parameters calibrated to cadaveric specimens spanning a range of bone mineral densities (BMD). Additionally, an alternative model configuration was developed that included consideration of bone marrow, with bone and marrow material parameters assigned to elements randomly according to bone volume (BV%) measurements of experimental specimens, owing to the non-uniform nature of trabecular bone tissue microstructure.Statistical analysis found significant correlation between the shapes of the numerical and experimental force-displacement curves. FE models accurately captured the bone densification patterns observed experimentally. Inclusion of marrow elements offered improved response prediction of the flat-tip indenter tests.Ultimately, the developed approach demonstrates the ability of a generalizable continuum-level SPH approach to capture bone variability using clinical bone imaging metrics without needing detailed image-based geometries, a significant step towards simplified subject-specific modeling of implant subsidence.

Real-world efficacy of a teriparatide biosimilar (RGB-10) compared with reference teriparatide on bone mineral density, trabecular bone score, and bone parameters assessed using quantitative ultrasound, 3D-SHAPER® and high-resolution peripheral computer tomography in postmenopausal women with osteoporosis and very high fracture risk.

To compare the therapeutic efficacy of a teriparatide biosimilar (RGB-10) with reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high fracture risk. A retrospective analysis of 25 postmenopausal female patients treated for osteoporosis with RGB-10 for 24months and a matched cohort of 25 patients treated with reference teriparatide. The following outcomes were assessed at baseline, 12 and 24months: bone mineral density (BMD) at the lumbar spine, femoral neck and total hip using dual-energy x-ray absorptiometry (DXA) and integral, trabecular and cortical volumetric and surface BMD using 3D-SHAPER® imaging, trabecular bone score (TBS), quantitative ultrasound (QUS) measurements, and high-resolution peripheral quantitative computed tomography (HRpQCT) imaging of the radius and tibia. No significant differences were observed between treatment groups in any of the measured parameters of BMD or bone health at baseline as well as in any timepoint when assessed using these various diagnostic methods. Both compounds provided equivalent significant improvements from baseline in measures of osteoporosis and fracture risk. The results of the analysis demonstrate the therapeutic equivalence of the teriparatide biosimilar (RGB-10) to reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high risk of fracture.