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Purpose: To determine whether a 12-week, lower body-targeted aqua-plyometric (AquaPlyo) exercise program could improve muscle strength, bone mineral properties, and physical fitness in patients with juvenile idiopathic arthritis. Methods: A randomized controlled trial was adopted and included 48 patients with polyarticular juvenile idiopathic arthritis (age: 12–18 y). Patients were assigned to undergo either AquaPlyo exercises (AquaPlyo group, n = 24) or standard exercises (control group, n = 24). The outcome measures were assessed pretreatment and posttreatment and included concentric quadriceps peak torque, bone mineral properties (areal bone mineral density [BMD], volumetric BMD, bone mineral content, and BMD Z score), and physical fitness. Results: A significant posttreatment increase in the concentric quadriceps peak torque was detected in the AquaPlyo group compared with the control group (either at an angular velocity of 90°/s [right side: P =.016, left side: P =.025] or 180°/s [right side: P =.007, left side: P =.029]). Besides, a considerably greater improvement in the areal BMD (P =.0006), volumetric BMD (P =.027), bone mineral content (P =.002), and BMD Z score (P =.0004) was observed in the AquaPlyo group. Moreover, a remarkably greater rise in the physical fitness (P <.001) was revealed in the AquaPlyo group. Conclusion: AquaPlyo training can efficiently enhance muscle strength, improve bone mineral properties, and boost physical fitness in patients with juvenile idiopathic arthritis. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a heterogeneous heritable skeletal dysplasia characterized by bone fragility and deformity, growth deficiency, and other secondary connective tissue defects. OI is now understood as a collagen-related disorder caused by defects of genes whose protein products interact with collagen for folding, post-translational modification, processing and trafficking, affecting bone mineralization and osteoblast differentiation. This review provides the latest updates on genetics of OI, including new developments in both dominant and rare OI forms, as well as the signaling pathways involved in OI pathophysiology. There is a special emphasis on discoveries of recessive mutations in TENT5A, MESD, KDELR2 and CCDC134 whose causality of OI types XIX, XX, XXI and XXI, respectively, is now established and expends the complexity of mechanisms underlying OI to overlap LRP5/6 and MAPK/ERK pathways. We also review in detail new discoveries connecting the known OI types to each other, which may underlie an eventual understanding of a final common pathway in OI cellular and bone biology. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a rare congenital bone dysplasia characterized by high fracture rates and broad variations in clinical manifestations ranging from mild to increasingly severe and perinatal lethal forms. The underlying mutations affect either the synthesis or processing of the type I procollagen molecule itself or proteins that are involved in the formation and mineralization of the collagen matrix. Consequently, the collagen forming cells, the osteoblasts, become broadly dysfunctional in OI. Strikingly, hypermineralized bone matrix seems to be a frequent feature in OI, despite the variability in clinical severity and mutations in the so far studied different forms of human OI. While the causes of the increased mineral content of the bone matrix are not fully understood yet, there is evidence that the descendants of the osteoblasts, the osteocytes, which play a critical role not only in bone remodeling, but also in mineralization and sensing of mechanical loads, are also highly dysregulated and might be of major importance in the pathogenesis of OI. In this review article, we firstly summarize findings of cellular abnormalities in osteoblasts and osteocytes, alterations of the organic matrix, as well as of the microstructural organization of bone. Secondly, we focus on the hypermineralization of the bone matrix in OI as observed in several different forms of human OI as well as in animal models, its measurement and potential mechanical implications and its effect on the bone mineral density measured by dual X-ray absorptiometry. Thirdly, we give an overview of established medication treatments of OI and new approaches with a focus of their known or possible effects on the bone material, particularly on bone matrix mineralization. [ABSTRACT FROM AUTHOR]

Simple Summary: Phosphorus is a very important nutrient in poultry feeding, and it is involved in many vital metabolic functions and is also a constituent of bones. Despite this, poultry diets have a very low phosphorous availability, which is commonly compensated with the dietary supplementation with inorganic sources of phosphorous and phytases. This study investigated nutritional conditioning with low-phosphorous diets during the first week of life as a strategy to improve the efficiency of phosphorous utilization in broiler chickens. No effect of conditioning on the overall performance was observed, despite evidence for reduced phosphorous excretion, increased duodenal gene expression for phosphorous transporter SLC34A2, and improved phosphorous digestibility and tibia mineralization. It is concluded that phosphorous nutritional conditioning in early life has the potential to increase the dietary phosphorous utilization in poultry, although additional research is required to optimize the duration and extent of the conditioning protocol, as well as to quantify to which extent the dietary supplementation with inorganic phosphorous could be reduced with this strategy. Phosphorous is essential for many metabolic functions and the constitution of bones. Poultry have limited ability to use phosphorous from diets, which is mainly excreted and causes environmental concern. For this reason, diets are commonly supplemented with inorganic phosphorus and phytases. It has been suggested that chickens can adapt to an early nutrient restriction by increasing its efficiency of utilization, an adaptation that has been defined as nutritional conditioning. The aim of this study was to investigate a strategy of phosphorous nutritional conditioning by feeding low phosphorous diets during the first week of life as a strategy to improve the efficiency of phosphorous utilization later in life. To test this, 600 male broiler chickens were fed either a standard (control group) or a phosphorous-deficient diet (conditioned group) during the first week of life. Later in life, the effect of conditioning was tested using standard or P-deficient diets during the finishing phase (21–43 d). Conditioning did not affect overall performance, despite finding evidence for reduced relative phosphorous excretion between days 19 to 21, increased duodenal gene expression for the phosphorous transporter SLC34A2 at day 30 (−6% and +17%, respectively), and tendencies for improved phosphorous digestibility (+7%) and tibia mineralization (+6%) at the end of the trial. It is concluded that phosphorous nutritional conditioning early in life can increase subsequent dietary phosphorous utilization and bone mineralization in poultry, although it may not be able to counteract severe phosphorous deficiencies. Further research is required to assess the extent to which phosphorous supplementation in post-conditioning diets may be reduced with this strategy without compromising performance. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine how different sources of Zn, Mn, and Cu in the feed without and with phytase affect prececal myo-inositol hexakisphosphate (InsP6) breakdown to myo-inositol (MI), prececal P digestibility, bone mineralization, and expression of mineral transporters in the jejunum of broiler chickens. A total of 896 male broiler chicks (Cobb 500) were distributed to 7 diets with 8 replicate pens (16 birds per floor pen). Experimental diets were fed from day 0 to 28. Diets were without or with phytase supplementation (0 or 750 FTU/kg) and were supplemented with three different trace mineral sources (TMS: sulfates, oxides, or chelates) containing 100 mg/kg Zn, 100 mg/kg Mn, and 125 mg/kg Cu. Prececal InsP6 disappearance and P digestibility were affected by interaction (phytase × TMS: P ≤ 0.010). In diets without phytase supplementation, prececal InsP6 disappearance and P digestibility were greater (P ≤ 0.001) in birds fed chelated minerals than in birds fed sulfates or oxides. However, no differences were observed between TMS in diets with phytase supplementation. Ileal MI concentration was increased by exogenous phytase but differed depending on TMS (phytase × TMS: P ≤ 0.050). Tibia ash concentration as well as Zn and Mn concentration in tibia ash were increased by phytase supplementation (P < 0.010), but the Cu concentration in tibia ash was not (P > 0.050). Gene expression of the assayed mineral transporters in the jejunum was not affected by diet (P > 0.050), except for Zn transporter 5 (phytase × TMS: P = 0.024). In conclusion, the tested TMS had minor effects on endogenous phytate degradation in the digestive tract of broiler chickens. However, in phytase-supplemented diets, the choice of TMS was not relevant to phytate degradation under the conditions of this study. [ABSTRACT FROM AUTHOR]

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Background: Risperidone is one of the most reliable and effective antipsychotics for schizophrenia treatment. However, the mechanism of action of risperidone is not yet fully understood. Traf2 and Nck-interacting protein kinase (TNIK), a schizophrenia susceptibility gene, is associated with risperidone treatment response. Our previous in vitro experiments confirmed that downregulated TNIK affected the effect of risperidone on downstream targets. However, the effect of downregulated TNIK on risperidone-induced molecular expression remains to be further explored. Methods: Transcriptome analysis was performed on U251 cells subjected to risperidone, TNIK siRNA, and no treatment, respectively. Compared to the notreatment group, two groups of DEGs were screened out and then intersected with the schizophrenia-related genes to screen the cross-talk genes. Those DEGs were analyzed using GO and KEGG. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network for the cross-talk gene. Results: The results showed that the parathyroid hormone synthesis, secretion, and action were significantly enriched after risperidone treatment. Downregulated TNIK could have an impact on the collagen-containing extracellular matrix, signaling receptor activator activity, and PI3K-Akt signaling pathway. Interestingly, bone mineralization function and calcium signaling pathway were enriched in the cross-talk genes. Additionally, FGFR2, FGF1, and FGFR might be the potential targets for TNIK affecting the effects of risperidone. Conclusion: The study indicated that risperidone primarily influences functions and/or pathways associated with bone metabolism, potentially contributing to the adverse effect of osteoporosis. Our study may offer a novel perspective on investigating the mechanisms underlying the adverse effects of risperidone. [ABSTRACT FROM AUTHOR]

Different biological models can be evaluated using mathematical models in both qualitative and quantitative ways. A fractional bone mineralization model involving Caputo’s fractional derivative is presented in this work. The fractional mathematical model is beneficial because of its memory carrying property. An appropriate fractional order of the derivative can be chosen that is more closely related to experimental or actual data. The dynamical system of equations for the process of bone mineralization is examined qualitatively and quantitatively in this article. A numerical simulation has been performed for the model. The model’s parameters have undergone sensitivity analysis and their effects on the model variables have been explored. By studying the mineralization patterns in bone, different diseases can be cured, and it can also be examined how the deviations from healthy mineral distributions lead to specific bone diseases. [ABSTRACT FROM AUTHOR]

Craniometaphyseal Dysplasia (CMD) is a rare skeletal disorder that can result from mutations in the ANKH gene. This gene encodes progressive anksylosis (ANK), which is responsible for transporting inorganic pyrophosphate (PPi) and ATP from the intracellular to the extracellular environment, where PPi inhibits bone mineralization. When ANK is dysfunctional, as in patients with CMD, the passage of PPi to the extracellular environment is reduced, leading to excess mineralization, particularly in bones of the skull. Zebrafish may serve as a promising model to study the mechanistic basis of CMD. Here, we provide a detailed analysis of the zebrafish Ankh paralogs, Ankha and Ankhb, in terms of their phylogenic relationship with ANK in other vertebrates as well as their spatiotemporal expression patterns during zebrafish development. We found that a closer evolutionary relationship exists between the zebrafish Ankhb protein and its human and other vertebrate counterparts, and stronger promoter activity was predicted for ankhb compared to ankha. Furthermore, we noted distinct temporal expression patterns, with ankha more prominently expressed in early development stages, and both paralogs also being expressed at larval growth stages. Whole-mount in situ hybridization was used to compare the spatial expression patterns of each paralog during bone development, and both showed strong expression in the craniofacial region as well as the notochord and somites. Given the substantial overlap in spatiotemporal expression but only subtle patterning differences, the exact roles of these genes remain speculative. In silico analyses predicted that Ankha and Ankhb have the same function in transporting PPi across the membrane. Nevertheless, this study lays the groundwork for functional analyses of each ankh paralog and highlights the potential of using zebrafish to find possible targeted therapies for CMD. [ABSTRACT FROM AUTHOR]

The Forkhead box transcription factors FOXC1 and FOXC2 are expressed in condensing mesenchyme cells at the onset of endochondral ossification. We used the Prx1-cre mouse to ablate Foxc1 and Foxc2 in limb skeletal progenitor cells. Prx1-cre;Foxc1Δ/Δ; Foxc2Δ/Δ limbs were shorter than controls, with worsening phenotypes in distal structures. Cartilage formation andmineralization was severely disrupted in the paws. The radius and tibia were malformed, whereas the fibula and ulna remained unmineralized. Chondrocyte maturation was delayed, with fewer Indian hedgehog-expressing, prehypertrophic chondrocytes forming and a smaller hypertrophic chondrocyte zone. Later, progression out of chondrocyte hypertrophy was slowed, leading to an accumulation of COLX-expressing hypertrophic chondrocytes and formation of a smaller primary ossification center with fewer osteoblast progenitor cells populating this region. Targeting Foxc1 and Foxc2 in hypertrophic chondrocytes with Col10a1-cre also resulted in an expanded hypertrophic chondrocyte zone and smaller primary ossification center.Our findings suggest that FOXC1 and FOXC2 direct chondrocyte maturation towards hypertrophic chondrocyte formation. At later stages, FOXC1 and FOXC2 regulate function in hypertrophic chondrocyte remodeling to allow primary ossification center formation and osteoblast recruitment. [ABSTRACT FROM AUTHOR]

Physiological processes within the human body are regulated in approximately 24‐h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders. [ABSTRACT FROM AUTHOR]

Epimedium is thought to enhance the integrity of tendons and bones, ease joint discomfort and rigidity and enhance kidney function. Although glucocorticoids are commonly used in clinical practice, the mechanism by which the active compound Epimedin C (EC) alleviates glucocorticoid‐induced osteoporosis (GIOP) is not well understood. The therapeutic potential of EC in treating GIOP was evaluated using alizarin red S staining, calcein immersion and fluorescence imaging, and bone mineralization, bone mass accumulation and bone density in zebrafish larvae were determined. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the key signalling pathways related to bone development were identified. A protein–protein interaction network (PPIN) was constructed to identify osteoclast characteristic genes and the findings were verified using real‐time quantitative PCR (RT‐qPCR). The bone tissue damage caused by prednisolone was reduced by EC. It also altered physiological processes, improved bone density, boosted mineralization and increased bone mass and activity. Subsequent empirical investigations showed that EC impacted the major signalling pathways involved in bone development, such as osteoclast differentiation, oestrogen, MAPK, insulin resistance, PPAR and AMPK signalling pathways. It also decreased the expression of genes typical of osteoclasts. The results of our study uncover a previously unknown function of EC in controlling bone formation and emphasize the potential of EC as a therapeutic target. The osteoprotective effect of EC indicates its potential as a cost‐effective strategy for treating GIOP. [ABSTRACT FROM AUTHOR]

ABSTRACT Sunflower cake is an alternative feed with nutritional potential to be used in poultry feeding. However, the high fiber content and the presence of antinutritional factors can compromise the availability of nutrients in the diet and influence the bone development of pullets, which can be mitigated with the dietary inclusion of exogenous enzymes. In this context, the objective of this study was to evaluate the effect of multi-enzyme supplementation in rations containing sunflower cake to pullets on mineral digestibility and quality and bone mineral composition. A total of 1020 pullets 7-weeks-age from the commercial strain Hy-Line, 540 white pullets and 480 brown pullets, were distributed in a randomized experimental design in a 2×2+1 factorial arrangement, with two sunflower cake levels (10 and 20% for white pullets and 12 and 24 % for brown pullets); two ways of enzymatic supplementation (absence and presence of multi-enzyme complex), and one control diet based on corn and soybean meal, totaling five treatments with six replicates of 18 white pullets and 16 brown pullets. Between week 14 and week 15, a metabolic trial was performed to determine the digestibility coefficient of ration minerals. To assess bone quality of the tibia and femur, one pullet of the 12th and 17th week of age was selected and killed. There was no significant interaction between the tested factors (sunflower cake x multi-enzyme complexes) for any of the variables studied. The inclusion level of sunflower cake did not influence the growth and bone quality parameters of the pullets during the growing phase. However, a presence of the multi-enzyme complex provided significant improvements in Ca, P and Mg digestibility coefficient. It is concluded that the multi-enzyme supplementation in the diets increases the digestibility of the mineral in the rations, contributing to the maintenance of bone quality of pullets fed with up to 24% sunflower cake.

Simple Summary: Supplementing piglets and growing–finishing pigs' diets with a new biosynthetic 6-phytase can be an effective replacement for inorganic phosphorus to improve growth performance, feed efficiency, bone mineralization, and availability of nutrients in weaned piglets and growing–finishing pigs. Phytase addition improved the availability of nutrients, especially of phosphorus and calcium and, therefore, growth performance and bone mineralization in weaning and growing–finishing pigs fed diets reduced in digestible phosphorus and calcium. In addition, the present study highlights that the main pathways (fecal and urinary) of phosphorus and calcium excretion in weaned piglets can be influenced not only by dietary levels of these minerals but also by phytase supplementation. Two experiments were performed to evaluate the effect of a biosynthetic 6-phytase added at 500 phytase unit (FTU)/kg diet on growth performance, bone mineralization, and nutrient digestibility and retention in weaned piglets and growing–finishing pigs. Experiments were performed on 90 weaned male and female piglets with an average initial body weight (BW) at 7.7 ± 0.73 kg, 26 days of age) and 300 male and female growing pigs (initial BW: 21.0 ± 3.44 kg) for 43 and 98 days in experiments 1 and 2, respectively. In each experiment, the animals were assigned to one of three treatments according to a randomized complete block design. The treatments consisted of a positive-control (PC) diet formulated to meet nutrient requirements; a negative-control (NC) diet reduced similarly in calcium (Ca) and digestible P by 0.15 and 0.12% points in phases 1 and 2, respectively, in piglets and by 0.14, 0.11, and 0.10% points, respectively, in phases 1, 2, and 3 in growing–finishing pigs, compared with PC diet; and a NC diet supplemented with the new 6-phytase at 500 FTU/kg diet (PHY). The dietary P and Ca depletion reduced (p < 0.05) the final BW (−11.9%; −7.8%,), average daily gain (ADG, −17.8%; −10.1%), average daily feed intake (ADFI, −9.9%; −6.0%), gain-to-feed (G:F) ratio (−8.9%; −4.6%), and apparent total tract digestibility (ATTD) of P (−7.7% points; −6.7% points) in nursery piglets and growing pigs, respectively. It also decreased (p < 0.001) P and Ca retention by 6.1 and 9.4% points, respectively, in nursery pigs and ash, P, and Ca contents in metacarpal bones by 18.4, 18.4, and 16.8%, respectively, in growing pigs. Compared to animals fed the NC diet, phytase supplementation improved (p < 0.001) the final BW (+7.7%; +11.3%), ADG (+12.5%; +15.0%), G:F ratio (+8.4%; +5.8%), ATTD of Ca (+10.8% points; +7.2% points), and ATTD of P (+18.7% points; +16.6% points) in weaned piglets and growing pigs, respectively. In addition, phytase also increased (p < 0.001) P and Ca retention by 6.1 and 9.4% points, respectively, in nursery pigs and ash, P, and Ca contents in metacarpal bones by 17.7, 15.0, and 15.2%, respectively, in growing pigs. The final BW, ADG, G:F ratio, and bone traits in animals fed the NC diet supplemented with phytase were comparable to animals fed the PC diet. This finding indicates the ability of this novel biosynthetic phytase to restore performance and bone mineralization by improving the availability of P and Ca in piglets and growing pigs fed P- and Ca-deficient diets. [ABSTRACT FROM AUTHOR]

Background: In standard fortification of human milk (HM), the HM macronutrient content is assumed, and a fixed amount of a multinutrient fortifier is added to achieve recommended nutrient intakes. In target fortification, the HM macronutrient content is regularly measured, guiding the addition of modular macronutrient supplements to the fortified HM, to achieve the nutritional targets more precisely. Objective: The study aimed to investigate whether this addition of modular supplements, unaccompanied by mineral supplementation, predispose to metabolic bone disease (MBD). Methods: This is a secondary analysis of a larger study of infants born with <33 weeks gestational age. Fortifications based on the assumed (Group 1) or measured (Group 2) of the HM macronutrient content were compared, using low serum phosphate levels as an indicator of MBD, and length growth as a surrogate of bone growth. Results: Eighty‑four infants were included, 35 in Group 1 and 49 in Group 2. During the exposure period, infants of Group 2 received higher mean fat (6.1 vs. 5.3 g/kg/day, P < 0.001) and carbohydrate (13.0 vs. 11.7 g/kg/day, P < 0.001) intakes; in addition, they exhibited lower mean serum phosphate (5.5 vs. 6.0 mg/dL, P = 0.022) and faster mean length velocity (1.06 vs. 0.89 cm/week, P = 0.003). Conclusions: These findings suggest that feeding fortified HM with extra fat and carbohydrate content, unaccompanied by mineral supplementation, promotes increased bone growth, as indicated by accelerated length growth, but with insufficiently mineralized osteoid, indicated by low serum phosphate levels. Intervention studies using direct biomarkers of bone mass content and mineral density are necessary to corroborate our findings. [ABSTRACT FROM AUTHOR]

The objective of the present study was to improve our understanding of the complex biological process of bone mineralization by performing mathematical modeling with the Caputo-Fabrizio fractional operator. To obtain a better understanding of Komarova's bone mineralization process, we have thoroughly examined the boundedness, existence, and uniqueness of solutions and stability analysis within this framework. To determine how model parameters affect the behavior of the system, sensitivity analysis was carried out. Furthermore, the fractional Adams-Bashforth method has been used to carry out numerical and graphical simulations. Our work is significant owing to its comparison of fractional- and integer-order models, which provides novel insight into the effectiveness of fractional operators in representing the complex dynamics of bone mineralization.

Despite advances in neonatal care, metabolic bone disease of prematurity (MBDP) remains a common problem in preterm infants. The development of non-invasive and affordable diagnostic approaches can be highly beneficial in the diagnosis and management of preterm infants at risk of MBDP. In this study, we present an ultrasound method called pulsed vibro-acoustic analysis to investigate the progression of bone mineralization in infants over time versus weight and postmenstrual age. The proposed pulsed vibro-acoustic analysis method is used to evaluate the vibrational characteristics of the bone. This method uses the acoustic radiation force of ultrasound to vibrate the bone. The generated acoustic waves are detected using a hydrophone placed on the skin over the tibia. The frequency of vibration and the speeds of received acoustic waves have information regarding the material property of the bone. We examined the feasibility of this method through an in vivo study consisting of 25 preterm and 10 full term infants. The pulsed vibro-acoustic data were acquired longitudinally in preterm infants with multiple visits and at a single visit in full term infants. Speed of sound and mean peak frequency of slow and fast sound waves recorded by hydrophone were used to analyze bone mineralization progress. Linear mixed model was used for statistical analysis in characterizing the mineralization progress in preterm infants compared to data from full term subjects. Significance changes in wave parameters (speed of sound and mean peak frequency) with respect to the postmenstrual age and weight in preterm infants were observed with p-values less than 0.05. Statistical significances in speed of sound measurement for both fast and slow waves were observed between preterm and full term infants, with p-values of

Study aim: This cross-sectional study examined the relationship between biological factors, physical activity (PA), bone turnover markers (BTMs) and bone mineral density (BMD) in women with subclinical hypothyroidism (SCH) and healthy.

Phosphorous is essential for many metabolic functions and the constitution of bones. Poultry have limited ability to use phosphorous from diets, which is mainly excreted and causes environmental concern. For this reason, diets are commonly supplemented with inorganic phosphorus and phytases. It has been suggested that chickens can adapt to an early nutrient restriction by increasing its efficiency of utilization, an adaptation that has been defined as nutritional conditioning. The aim of this study was to investigate a strategy of phosphorous nutritional conditioning by feeding low phosphorous diets during the first week of life as a strategy to improve the efficiency of phosphorous utilization later in life. To test this, 600 male broiler chickens were fed either a standard (control group) or a phosphorous-deficient diet (conditioned group) during the first week of life. Later in life, the effect of conditioning was tested using standard or P-deficient diets during the finishing phase (21–43 d). Conditioning did not affect overall performance, despite finding evidence for reduced relative phosphorous excretion between days 19 to 21, increased duodenal gene expression for the phosphorous transporter SLC34A2 at day 30 (−6% and +17%, respectively), and tendencies for improved phosphorous digestibility (+7%) and tibia mineralization (+6%) at the end of the trial. It is concluded that phosphorous nutritional conditioning early in life can increase subsequent dietary phosphorous utilization and bone mineralization in poultry, although it may not be able to counteract severe phosphorous deficiencies. Further research is required to assess the extent to which phosphorous supplementation in post-conditioning diets may be reduced with this strategy without compromising performance.

Recent investigations into mechanisms behind the development of osteoporosis suggest that suppressing PPARγ-mediated adipogenesis can improve bone formation and bone mineral density. In this study, we investigated a co-treatment strategy to enhance bone formation by combining NELL-1, an osteogenic molecule that has been extensively studied for its potential use as a therapeutic for osteoporosis, with two methods of PPARγ suppression. First, we suppressed PPARγ genetically using lentiviral PPARγ-shRNA in immunocompromised mice for a proof of concept. Second, we used a PPARγ antagonist to suppress PPARγ pharmacologically in immunocompetent senile osteopenic mice for clinical transability. We found that the co-treatment strategy significantly increased bone formation, increased the proliferation stage cell population, decreased late apoptosis of primary mouse BMSCs, and increased osteogenic marker mRNA levels in comparison to the single agent treatment groups. The addition of PPARγ suppression to NELL-1 therapy enhanced NELL-1s effects on bone formation by upregulating anabolic processes without altering NELL-1s inhibitory effects on osteoclastic and adipogenic activities. Our findings suggest that combining PPARγ suppression with therapeutic NELL-1 may be a viable method that can be further developed as a novel strategy to reverse bone loss and decrease marrow adiposity in age-related osteoporosis.

The phosphodiesterase enzymes mediate calcium-phosphate deposition in various tissues, although which enzymes are active in bone mineralization is unclear. Using gene array analysis, we found that a member of ecto-nucleotide pyrophosphatase/phosphodiesterase family, ENPP2, was strongly down-regulated with age in stromal stem cells that produce osteoblasts and make bone. This is in keeping with reduced bone formation in older animals. Thus, we hypothesized that ENPP2 is, at least in part, an early mediator of bone formation and thus may reflect reduced bone formation with age. Since ENPP2 has not previously been shown to have a role in osteoblast differentiation, we studied its effect on bone differentiation from stromal stem cells, verified by flow cytometry for stem cell antigens. In these remarkably uniform osteoblast precursors, we did transfection with ENPP2 DsiRNA, scrambled DsiRNA, or no transfection to make cells with normal or greatly reduced ENPP2 and analyzed osteoblast differentiation and mineralization. Osteoblast differentiation down-regulation was shown by alizarin red binding, silver staining, and alkaline phosphatase activity. Differences were confirmed by real-time PCR for alkaline phosphatase (ALPL), osteocalcin (BGLAP), and ENPP2 and by Western Blot for Enpp2. These were decreased, ~50%, in osteoblasts transfected with ENPP2 DsiRNA compared with cells transfected with a scrambled DsiRNA or not transfected (control) cells. This finding is the first evidence for the role of ENPP2 in osteoblast differentiation and mineralization. [ABSTRACT FROM AUTHOR]

There is still limited understanding of the microstructural reasons for the higher susceptibility to fractures in individuals with type 2 diabetes mellitus (T2DM). In this study, we examined bone mineralization, osteocyte lacunar parameters, and microhardness of the femoral neck trabeculae in 18 individuals with T2DM who sustained low-energy fracture (T2DMFx: 78 ± 7 years, 15 women and 3 men) and 20 controls (74 ± 7 years, 16 women and 4 men). Femoral necks of the T2DMFx subjects were obtained at a tertiary orthopedic hospital, while those of the controls were collected at autopsy. T2DMFx individuals had lower trabecular microhardness (P  = .023) and mineralization heterogeneity (P  = .001), and a tendency to a lower bone area with mineralization above 95th percentile (P  = .058) than the controls. There were no significant intergroup differences in the numbers of osteocyte lacunae per bone area, mineralized lacunae per bone area, and total lacunae per bone area (each P  > .05). After dividing the T2DMFx group based on the presence of vascular complications (VD) to T2DMFxVD (VD present) and T2DMFxNVD (VD absent), we observed that microhardness was particularly reduced in the T2DMFxVD group (vs. control group, P  = .02), while mineralization heterogeneity was significantly reduced in both T2DMFx subgroups (T2DMFxNVD vs. control, P  = .002; T2DMFxVD vs. control, P  = .038). The observed changes in mineralization and microhardness may contribute to the increased hip fracture susceptibility in individuals with T2DM. [ABSTRACT FROM AUTHOR]

Bone loss is a well-known phenomenon in the older population leading to increased bone fracture risk, morbidity, and mortality. Supplementation of eggshell membrane (ESM) is evaluated due to its possible application to prevent bone loss and usage in osteoporosis therapy. The similar organic chemical composition of ESM and human bone is described in detail as both mainly consist of collagen type I, chondroitin sulfate, dermatan sulfate, hyaluronic acid and elastan. ESM and its components are reported to improve mineralization in bone tissue. In many studies ESM intake reduced pain in patients with joint disorders and reduced inflammatory processes. Additionally, ESM improved calcium uptake in human cells. These findings in comparison with a clinical pilot study reporting pain reduction in osteoporotic patients and increased osteoblast activity in in vitro assays support ESM to be a beneficial supplement for bone health. In this systematic review we combined chemical structure analysis with clinical studies to give a more comprehensive picture with novel explanations.

This investigation was done to determine how much zinc (Zn) the stinging catfish, Heteropneustes fossilis, needs in its diet. Five isonitrogenous (34.5% protein) and isolipidic (6.0% lipid) diets were prepared to contain graded levels of Zn (0, 10, 20, 30, and 40 mg kg−1), supplied as zinc sulfate (ZnSO4·7H2O), and referred to as Zn0, Zn10, Zn20, Zn30, and Zn40, respectively. A total of 600 fish (initial body weight: 1.41 ± 0.02 g) were stocked in 15 glass aquaria (40 fish/aquarium), each with 180 L water capacity. For ten weeks, each diet was hand fed to three groups of fish twice daily until they appeared satisfied. The highest weight gain and specific growth rate, and lowest feed conversion ratio were recorded in fish fed with a 30 mg Zn kg−1 diet. Zn contents in bone and muscle linearly increased up to 30 mg kg−1 Zn and then remained stable, while iron (Fe) and copper (Cu) contents in bone and muscle had an inverse pattern with the inclusion level of dietary Zn. Increasing dietary Zn levels up to 30 mg kg−1 was found to improve values of hematological parameters such as red blood cell (RBC), white blood cell (WBC), haemoglobin (Hb), and haematocrit (HCT). These values, however, decreased when the dietary Zn level was further increased. The serum alkaline phosphatase level was the highest in fish fed a diet containing 30 mg kg-1 of Zn. Regression analyses based on weight gain, specific growth rate, and bone and muscle Zn concentrations indicated that the optimum dietary Zn requirement for stinging catfish was in a range of 27.4–36.5 mg kg−1.

Three Ca-P deficient diets viz., Diet-1 (0.85%, 0.35%), Diet-2 (0.75%, 0.30%) and Diet-3 (0.65%, 0.25%) were prepared and supplemented with either bacterial or fungal origin phytase enzymes and were compared with a control diet (1.0% and 0.45%). A total of 280 broiler (Ross 308) chicks were randomly allocated into 7 treatments having 4 replicates of 10 chicks using a completely randomized design. The effect of bacterial phytase on the growth, FCR and carcass weight was significantly (P

Craniometaphyseal Dysplasia (CMD) is a rare skeletal disorder that can result from mutations in the ANKH gene. This gene encodes progressive anksylosis (ANK), which is responsible for transporting inorganic pyrophosphate (PPi) and ATP from the intracellular to the extracellular environment, where PPi inhibits bone mineralization. When ANK is dysfunctional, as in patients with CMD, the passage of PPi to the extracellular environment is reduced, leading to excess mineralization, particularly in bones of the skull. Zebrafish may serve as a promising model to study the mechanistic basis of CMD. Here, we provide a detailed analysis of the zebrafish Ankh paralogs, Ankha and Ankhb, in terms of their phylogenic relationship with ANK in other vertebrates as well as their spatiotemporal expression patterns during zebrafish development. We found that a closer evolutionary relationship exists between the zebrafish Ankhb protein and its human and other vertebrate counterparts, and stronger promoter activity was predicted for ankhb compared to ankha. Furthermore, we noted distinct temporal expression patterns, with ankha more prominently expressed in early development stages, and both paralogs also being expressed at larval growth stages. Whole-mount in situ hybridization was used to compare the spatial expression patterns of each paralog during bone development, and both showed strong expression in the craniofacial region as well as the notochord and somites. Given the substantial overlap in spatiotemporal expression but only subtle patterning differences, the exact roles of these genes remain speculative. In silico analyses predicted that Ankha and Ankhb have the same function in transporting PPi across the membrane. Nevertheless, this study lays the groundwork for functional analyses of each ankh paralog and highlights the potential of using zebrafish to find possible targeted therapies for CMD.

Three Ca-P deficient diets viz., Diet-1 (0.85%, 0.35%), Diet-2 (0.75%, 0.30%) and Diet-3 (0.65%, 0.25%) were prepared and supplemented with either bacterial or fungal origin phytase enzymes and were compared with a control diet (1.0% and 0.45%). A total of 280 broiler (Ross 308) chicks were randomly allocated into 7 treatments having 4 replicates of 10 chicks using a completely randomized design. The effect of bacterial phytase on the growth, FCR and carcass weight was significantly (P < 0.05) higher in chicks on Diet-1 compared to diet-3 (28 days). Bacterial phytase increased serum minerals (Ca and P) and tibia ash in diet-1 compared to Diet-3. Tibia Ca was significantly (P < 0.05) higher in the control and the three diets under bacterial phytase compared to other treatments. On Diet-3, more Ca and P were reflected in tibial by bacterial phytase but did not support the optimum growth performance of broiler chicks. In conclusion, the same phytase but of different origins might have specific individual effects on the growth performance, serum and tibia Ca and P in broilers. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Turner syndrome (TS) often face skeletal and muscular challenges, including reduced bone mineral density (BMD) and muscle weakness. This comprehensive study sheds light on the complex interplay between muscle strength, BMD, and metabolic and endocrine parameters in TS and healthy subjects. Methods: A cross-sectional study involving 42 TS patients and 70 healthy women was conducted. All patients had their BMD determined in the L1–L4 lumbar spine section and in the whole skeleton as well as the parameters of body fat mass (BF), and visceral fat mass (VF) were also determined. The maximum gripping force was measured with a hydraulic manual dynamometer. In addition, a number of blood hormonal and metabolic parameters were determined. Results: In the TS group, hand grip strength correlated positively with triglyceride levels but not with BMD. Healthy individuals had a positive link between hand grip strength and BMD, while patients with TS did not show a significant association between the two. A trend suggested that longer recombinant human growth hormone (rhGH) therapy might improve BMD in the L1–L4 region. Multiple linear regression analysis revealed that muscle strength assessment may be a potential exponent of reduced BMD, and also used clinically in young adult women but not in individuals with TS. Conclusions: The relationship between BMD variables and hand grip might differ between the two groups, potentially indicating distinct musculoskeletal characteristics in TS patients. Longer rhGH therapy in TS patients may have a positive effect on BMD in the L1–L4 region. Understanding the intricate relationships between these factors is important for optimizing clinical management strategies and improving the quality of life for TS patients. [ABSTRACT FROM AUTHOR]

The gut microbiome has been implicated in a multitude of human diseases, with emerging evidence linking its microbial diversity to osteoporosis. This review article will explore the molecular mechanisms underlying perturbations in the gut microbiome and their influence on osteoporosis incidence in individuals with chronic diseases. The relationship between gut microbiome diversity and bone density is primarily mediated by microbiome-derived metabolites and signaling molecules. Perturbations in the gut microbiome, induced by chronic diseases can alter bacterial diversity and metabolic profiles, leading to changes in gut permeability and systemic release of metabolites. This cascade of events impacts bone mineralization and consequently bone mineral density through immune cell activation. In addition, we will discuss how orally administered medications, including antimicrobial and non-antimicrobial drugs, can exacerbate or, in some cases, treat osteoporosis. Specifically, we will review the mechanisms by which non-antimicrobial drugs disrupt the gut microbiome's diversity, physiology, and signaling, and how these events influence bone density and osteoporosis incidence. This review aims to provide a comprehensive understanding of the complex interplay between orally administered drugs, the gut microbiome, and osteoporosis, offering new insights into potential therapeutic strategies for preserving bone health. [ABSTRACT FROM AUTHOR]

To evaluate the effect of exogenous phytase (Ronozyme HiPhos-L, produced by the strain of Aspergillus oryzae), 1050 one-day-old Ross-308 broilers with an initial average body weight of 50.29 ± 0.98 g were randomly assigned to one of seven dietary treatments with 10 replicates and 15 chicks/cage. During starter (d 1–7), grower (d 8–21), and finisher (d 21–35) periods, broilers were allowed to feed: positive control (PC), negative control (NC), and NC diet supplemented with 250, 500, 1000, 1500, and 3000 U/kg of phytase. Broilers fed NC diet supplemented with graded levels of phytase (250 U/kg to 3000 U/kg) showed a linear increase (p < 0.05) in body weight gain and feed intake during the starter and the overall trial period with no adverse effect on feed conversion ratio. The nutrient utilization of broilers showed neither an increase nor a decrease with the PC and NC diet until d 35 but when the NC diet was supplemented with a graded dose of phytase, the broilers showed a linear increase (p < 0.05) in dry matter, gross energy, calcium (Ca), ash, and phosphorus (P) utilization and a tendency to increase (p < 0.10) nitrogen retention at the end of the starter phase. Unlike the starter phase, broilers fed the PC diet showed increased (p < 0.05) ash and Ca retention at the end of the grower and finisher phase compared to those fed the NC diet. In addition, the phytase group showed a linear increase (p < 0.05) in ash, Ca, and P utilization at the end of d 21 and 35. Moreover, the inclusion of graded levels of phytase in the NC diet showed a linear increase (<0.0001) in bone (ash, Ca, and P) mineralization in broilers. Also, they showed a linear increase (p < 0.05) in gizzard weight, breast muscle, color of lightness, redness, and pH and a decreased cooking loss and drip loss. Though the standard diets were able to compensate for the P deficiency and promote performance and bone mineralization, the elevated (1000 FTU/kg) levels of phytase in the NC diet showed a higher response. Thus, we suggest that incorporating the exogenous enzyme phytase into the broiler feed in excess of 1000 units (U)/kg would be more beneficial to achieve better productivity. [ABSTRACT FROM AUTHOR]

Context: Childhood hyperphosphatasemia is usually transient and may be associated with infections. It remains less well known how hyperphosphatasemia is related to growth and bone mineralization. Objective: We explored alkaline phosphatase (ALP) concentrations and prevalence of hyperphosphatasemia, and their association with vitamin D, growth, infections, and bone parameters in healthy children. Methods: The study was a secondary analysis of a vitamin D intervention trial. Participants received vitamin D3 10 or 30 µg daily from age 2 weeks to 2 years. Children with data on ALP at 12 and/or 24 months (n = 813, girls 51.9%) were included. Anthropometrics and bone parameters were measured at 12 and 24 months. Infections were recorded prospectively by the parents. Results: Boys had higher ALP than girls at 12 months (median [IQR] 287 [241-345] U/L vs 266 [218-341] U/L; P = .02). At 24 months concentrations were lower than at 12 months (240 [202-284]; P < .001) but without sex difference. The prevalence of hyperphosphatasemia (ALP > 1000 U/L) at 12 months was 5.3% and at 24 months 0.6%. Body size, growth rate, and bone mineral content associated positively with ALP, while vitamin D intervention had no effect. Infants with hyperphosphatasemia were smaller than infants with ALP ≤ 1000 U/L. Hyperphosphatasemia was not associated with previous infections. Conclusion: Approximately 5% of infants had hyperphosphatasemia at 12 months, but <1% at 24 months. ALP concentrations and hyperphosphatasemia were associated with sex, anthropometry, and bone mineralization. Infections did not contribute to hyperphosphatasemia. [ABSTRACT FROM AUTHOR]

Two experiments were performed to evaluate the effect of a biosynthetic 6-phytase added at 500 phytase unit (FTU)/kg diet on growth performance, bone mineralization, and nutrient digestibility and retention in weaned piglets and growing–finishing pigs. Experiments were performed on 90 weaned male and female piglets with an average initial body weight (BW) at 7.7 ± 0.73 kg, 26 days of age) and 300 male and female growing pigs (initial BW: 21.0 ± 3.44 kg) for 43 and 98 days in experiments 1 and 2, respectively. In each experiment, the animals were assigned to one of three treatments according to a randomized complete block design. The treatments consisted of a positive-control (PC) diet formulated to meet nutrient requirements; a negative-control (NC) diet reduced similarly in calcium (Ca) and digestible P by 0.15 and 0.12% points in phases 1 and 2, respectively, in piglets and by 0.14, 0.11, and 0.10% points, respectively, in phases 1, 2, and 3 in growing–finishing pigs, compared with PC diet; and a NC diet supplemented with the new 6-phytase at 500 FTU/kg diet (PHY). The dietary P and Ca depletion reduced (p < 0.05) the final BW (−11.9%; −7.8%,), average daily gain (ADG, −17.8%; −10.1%), average daily feed intake (ADFI, −9.9%; −6.0%), gain-to-feed (G:F) ratio (−8.9%; −4.6%), and apparent total tract digestibility (ATTD) of P (−7.7% points; −6.7% points) in nursery piglets and growing pigs, respectively. It also decreased (p < 0.001) P and Ca retention by 6.1 and 9.4% points, respectively, in nursery pigs and ash, P, and Ca contents in metacarpal bones by 18.4, 18.4, and 16.8%, respectively, in growing pigs. Compared to animals fed the NC diet, phytase supplementation improved (p < 0.001) the final BW (+7.7%; +11.3%), ADG (+12.5%; +15.0%), G:F ratio (+8.4%; +5.8%), ATTD of Ca (+10.8% points; +7.2% points), and ATTD of P (+18.7% points; +16.6% points) in weaned piglets and growing pigs, respectively. In addition, phytase also increased (p < 0.001) P and Ca retention by 6.1 and 9.4% points, respectively, in nursery pigs and ash, P, and Ca contents in metacarpal bones by 17.7, 15.0, and 15.2%, respectively, in growing pigs. The final BW, ADG, G:F ratio, and bone traits in animals fed the NC diet supplemented with phytase were comparable to animals fed the PC diet. This finding indicates the ability of this novel biosynthetic phytase to restore performance and bone mineralization by improving the availability of P and Ca in piglets and growing pigs fed P- and Ca-deficient diets.

ABSTRACT: This study aimed to determine the effect of Zn source and dietary level on intestinal myo-inositol hexakisphosphate (InsP6) disappearance, intestinal accumulation of lower InsP and myo-inositol (MI), prececal mineral digestibility, bone mineralization, and Zn status of broilers without and with exogenous phytase in the feed. Male Ross 308 broilers were allocated in groups of 10 to 8 treatments with 8 pens each. Experimental diets were fed from d 7 to d 28 and contained 33 mg/kg dry matter plant-intrinsic Zn. Experimental factors were phytase supplementation (0 or 750 FTU/kg) and Zn source (none [0 mg/kg Zn], Zn-sulfate [30 mg/kg Zn], Zn-oxide [30 mg/kg Zn]). Additional treatments with 90 mg/kg Zn as Zn-sulfate or Zn-oxide and phytase were included to test the effect of Zn level. No Zn source or Zn level effects were observed for ADG, feed conversion ratio, prececal P digestibility, intestinal InsP6 disappearance, and bone ash concentration. However, those measurements were increased by exogenous phytase (P

ABSTRACT The aim of present study was to investigate the effect of phytase supplementation on growth performance, mineral digestibility, and tibia calcium and phosphorous in broilers fed low phosphorus diets. Three hundred broiler chicks were allotted to six different treatments with five replicates each (10 chicks/replicate). T1: Control, 0.5% available phosphorus (Av.P); T2: 0.35P, 0.35% Av.P; T3: 0.20P, 0.20% Av.P; T4: 0.35P-1Phy, diet 0.35P + 1000FTU/kg phytase; T5: 0.20P-2Phy, diet 0.20P + 2000 ftu/kg phytase; T6: 0.20P-3Phy, diet 0.20P + 3000 ftu/kg phytase. Feed intake and weight gain were higher (p=0.001) in broilers fed phytase supplemented diets. Feed conversion ratio was better (p

The gut microbiome has been implicated in a multitude of human diseases, with emerging evidence linking its microbial diversity to osteoporosis. This review article will explore the molecular mechanisms underlying perturbations in the gut microbiome and their influence on osteoporosis incidence in individuals with chronic diseases. The relationship between gut microbiome diversity and bone density is primarily mediated by microbiome-derived metabolites and signaling molecules. Perturbations in the gut microbiome, induced by chronic diseases can alter bacterial diversity and metabolic profiles, leading to changes in gut permeability and systemic release of metabolites. This cascade of events impacts bone mineralization and consequently bone mineral density through immune cell activation. In addition, we will discuss how orally administered medications, including antimicrobial and non-antimicrobial drugs, can exacerbate or, in some cases, treat osteoporosis. Specifically, we will review the mechanisms by which non-antimicrobial drugs disrupt the gut microbiome’s diversity, physiology, and signaling, and how these events influence bone density and osteoporosis incidence. This review aims to provide a comprehensive understanding of the complex interplay between orally administered drugs, the gut microbiome, and osteoporosis, offering new insights into potential therapeutic strategies for preserving bone health.

We studied osteoblast bone mineral transport and matrix proteins as a function of age. In isolated bone marrow cells from long bones of young (3 or 4 mo) and old (18 or 19 mo) mice, age correlated with reduced mRNA of mineral transport proteins: alkaline phosphatase (ALP), ankylosis (ANK), the Cl-/H+ exchanger ClC3, and matrix proteins collagen 1 (Col1) and osteocalcin (BGLAP). Some proteins, including the neutral phosphate transporter2 (NPT2), were not reduced. These are predominately osteoblast proteins, but in mixed cell populations. Remarkably, in osteoblasts differentiated from preparations of stromal stem cells (SSCs) made from bone marrow cells in young and old mice, differentiated in vitro on perforated polyethylene terephthalate membranes, mRNA confirmed decreased expression with age for most transport-related and bone matrix proteins. Additional mRNAs in osteoblasts in vitro included ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), unchanged, and ENPP2, reduced with age. Decrease with age in ALP activity and protein by Western blot was also significant. Transport protein findings correlated with micro-computed tomography of lumbar vertebra, showing that trabecular bone of old mice is osteopenic relative to young mice, consistent with other studies. Pathway analysis of osteoblasts differentiated in vitro showed that cells from old animals had reduced Erk1/2 phosphorylation and decreased suppressor of mothers against decapentaplegic 2 (Smad2) mRNA, consistent with TGFβ pathway, and reduced β-catenin mRNA, consistent with WNT pathway regulation. Our results show that decline in bone density with age reflects selective changes, resulting effectively in a phenotype modification. Reduction of matrix and mineral transport protein expression with age is regulated by multiple signaling pathways. [ABSTRACT FROM AUTHOR]

The sacroiliac auricular surface has a variable morphology and size. The impact of such variations on subchondral mineralization distribution has not been investigated. Sixty‐nine datasets were subjected to CT‐osteoabsorptiometry for the qualitative visualization of chronic loading conditions of the subchondral bone plate using color‐mapped densitograms based on Hounsfield Units in CT. Auricular surface morphologies were classified into three types based on posterior angle size: Type 1: >160°, Type 2: 130–160° and Type 3: <130°. Auricular surface size was categorized based on the mean value (15.4 cm2) separating the group into 'small' and 'large' joint surfaces. Subchondral bone density patterns were qualitatively classified into four color patterns: two marginal patterns (M1 and M2) and two non‐marginal patterns (N1 and N2) and each iliac and sacral surface was subsequently categorized. 'Marginal' meant that 60–70% of the surface was less mineralized compared with the highly dense regions and vice versa for the 'non‐marginal' patterns. M1 had anterior border mineralization and M2 had mineralization scattered around the borders. N1 had mineralization spread over the whole superior region, N2 had mineralization spread over the superior and anterior regions. Auricular surface area averaged 15.4 ± 3.6 cm2, with a tendency for males to have larger joint surfaces. Type 2 was the most common (75%) and type 3 the least common morphology (9%). M1 was the most common pattern (62% of surfaces) by sex (males 60%, females 64%) with the anterior border as the densest region in all three morphologies. Sacra have a majority of surfaces with patterns from the marginal group (98%). Ilia have mineralization concentrated at the anterior border (patterns M1 and N2 combined: 83%). Load distribution differences related to auricular surface morphology seems to have little effect on long‐term stress‐related bone adaptation visualized with CT‐osteoabsorptiometry. Higher iliac side mineralization was observed in larger joint surfaces and age‐related morphomechanical size alterations were seen in males. [ABSTRACT FROM AUTHOR]

Bone mineralization involves a complex orchestration of physico-chemical responses from the organism. Despite extensive studies, the detailed mechanisms of mineralization remain to be elucidated. This study aims to characterize bone mineralization using an in-vivo long bone fracture healing model in the rat. The spatio-temporal distribution of relevant elements was correlated to the deposition and maturation of hydroxyapatite and the presence of matrix remodeling compounds (MMP-13). Multi-scale measurements indicated that (i) zinc is required for both the initial mineral deposition and resorption processes during mature mineral remodeling; (ii) Zinc and MMP-13 show similar spatio-temporal trends during early mineralization; (iii) Iron acts locally and in coordination with zinc during mineralization, thus indicating novel evidence of the time-events and inter-play between the elements. These findings improve the understanding of bone mineralization by explaining the link between the different constituents of this process throughout the healing time. Bone mineralization involves a complex orchestration of physico-chemical responses from the organism, the detailed mechanisms of which remain to be elucidated. This study presents a highly novel multi-scale multi-modal investigation of bone mineralization using bone fracture healing as a model system. We present original characterization of tissue mineralization, where we relate the spatio-temporal distribution of important trace elements to a key matrix remodeling compound (MMP-13), the initial deposition and maturation of hydroxyapatite and further remodeling processes. This is the first time that mineralization has been probed down to the nanometric level, and where key mineralization components have been investigated to achieve a comprehensive and mechanistic understanding of the underlying mineralization processes during bone healing. [Display omitted] [ABSTRACT FROM AUTHOR]

Preterm birth and low birthweight have been associated with increased fracture risk in children. Our aim was to analyze bone fractures during childhood in preterm, and low‐birthweight newborns compared to full‐term and normal‐birthweight newborns. We conducted a nationwide register‐based cohort study in Finland from 1998 to 2017 and utilized the Medical Birth Register and Care Register for Health Care. All newborns alive 28 days after birth were included, and data on all fracture visits in specialized healthcare units were gathered. Incidences per 100,000 person‐years with 95% confidence intervals (CI) were calculated, and comparisons were made by incidence rate ratios (IRRs). Kaplan–Meier analysis was used to analyze the timing of fractures during childhood (0–20 years). We included a total of 997,468 newborns and 95,869 fractures; the mean follow‐up was 10.0 years, and the overall incidence of fractures was 963 per 100,000 person‐years. Very preterm (<32 gestational weeks) newborns had 23% lower fracture incidence than term newborns (IRR 0.77; CI: 0.70–0.85). Preterm newborns (32 to 36 gestational weeks) had a fracture rate (IRR 0.98; CI: 0.95–1.01) similar to that of term newborns. Birthweight showed a linear increase in the fracture rates as newborns with birthweight less than 1000 g had the lowest fracture incidence of 773 per 100,000 person‐years and the highest incidence (966 per 100,000 person‐years) was among newborns with birthweight 2500 g or more. Children born very preterm or with extremely low birthweight have in general a lower fracture incidence during childhood compared to children born full term and with normal birthweight. These findings possibly reflect, in addition to improvements of neonatal intensive care and early nutrition, the fact that childhood fracture incidences are more dependent on issues other than early life events. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Bone mineralization is critical to maintaining tissue mechanical function. The application of mechanical stress via exercise promotes bone mineralization via cellular mechanotransduction and increased fluid transport through the collagen matrix. However, due to its complex composition and ability to exchange ions with the surrounding body fluids, bone mineral composition and crystallization is also expected to respond to stress. Here, a combination of data from materials simulations, namely density functional theory and molecular dynamics, and experimental studies were input into an equilibrium thermodynamic model of bone apatite under stress in an aqueous solution based on the theory of thermochemical equilibrium of stressed solids. The model indicated that increasing uniaxial stress induced mineral crystallization. This was accompanied by a decrease in calcium and carbonate integration into the apatite solid. These results suggest that weight-bearing exercises can increase tissue mineralization via interactions between bone mineral and body fluid independent of cell and matrix behaviours, thus providing another mechanism by which exercise can improve bone health. This article is part of a discussion meeting issue 'Supercomputing simulations of advanced materials'. [ABSTRACT FROM AUTHOR]

Simple Summary: To understand the developmental changes in hare femora, this study aimed to examine the mechanical properties, mineralization, and general geometric properties of the thigh bone (femur) throughout the growth and maturation process. The study involved analyzing the strength, stiffness, bone mineral density, and structure of the femur in both young and adult hares. Additionally, the study sought to establish a connection between bone properties and the ecological functions of hares in their natural habitats. Understanding the changes in hare femora as they grow and mature is crucial for many reasons as it provides valuable insights into the effects of aging on wild hares, shedding light on their adaptability and survival strategies. Lagomorphs, which include hares, rabbits, and pikas, are herbivorous animals renowned for their exceptional running abilities. The femur, the largest and strongest bone in their bodies, plays a crucial role in supporting their weight and facilitating movement. This study aimed to investigate the structural and functional changes in the femora of hares during their development in a sex-dependent manner, and the influence of aging on femur structure and function. Various mechanical properties, including stiffness and strength, as well as densitometry and morphology, were evaluated. The study was conducted on n = 24 hares collected from a hunting district in the Lublin region of Poland and divided into four groups: young females, adult females, young males and adult males (n = 6 animals each). Dual-energy X-ray absorptiometry (DXA) was used to measure bone mineral content (BMC) and bone mineral density (BMD), and a three-point bending test was performed to assess mechanical properties. The findings revealed age-related differences in bone properties, with adult males exhibiting increased BMC, and BMD compared to young males. Geometrical properties of the femora mid-diaphysis, such as cortical index and cross-sectional area, remained relatively unchanged during maturation. Regarding mechanical properties, the femora of young males exhibited higher elastic work compared to those of young females, while the femora of adult males exhibited higher elastic and breaking work than those of adult females. The stiffness of femora was higher in adult females compared to young females. The results provide insights into the development and aging of hare femora and contribute to our understanding of the relationship between bone mechanical properties, musculoskeletal system, and aging in the wild. This knowledge can inform animal husbandry practices in captivity and enhance our broader understanding of the ecological functions of lagomorphs. [ABSTRACT FROM AUTHOR]

This study investigates the effects of Aspergillus meal prebiotic on a spectrum of parameters, including productive performance, bone mineralization, and intestinal integrity, in broiler chickens. Day-of-hatch Cobb 500 by-product male chicks (320 total) were randomly assigned to two experimental groups (G1 and G2) in floor pens (150×300 cm), each pen containing separate feeders and watering systems (8 replicates per treatment, 20 birds/pen). Chickens kept in G1 (control) were fed a basal diet, while those of G2 (treated) were fed a basal diet supplemented with 0.2% PRI-A-FERM. Performance parameters, including body weight (BW), body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR), were evaluated weekly from the 7th day to the end of the trial at 42 d. Fluorescein isothiocyanate-dextran (FITC-d) was administered via oral gavage to 3 chickens/replicate (n = 24), and blood was collected on 21d and on 42d to determine serum concentration of FITC-d as a biomarker to evaluate intestinal permeability and peptide YY as an indirect biomarker to evaluate short chain fatty acids. Chickens that received the Aspergillus meal prebiotic showed a significant increase in BW, BWG, and FI on days 14, 21, 28, 35, and 42 (P<0.05) and a significant reduction in FCR on days 28, 35, and 42 of evaluation compared to control. Moreover, chickens that were supplemented with the Aspergillus meal prebiotic showed a significant reduction in serum concentrations of FITC-d on both days of evaluation, as well as a significant increase in serum concentration of peptide YY. Additionally, treated animals significantly increased bone strength, total bone ash, and calcium and phosphorous content at both evaluation times compared to the control. In summary, the results of this study suggest that Aspergillus meal prebiotic supplementation can positively influence productive parameters, bone mineralization, and intestinal integrity in broiler chickens. The observed improvements underscore the importance of gut health in overall poultry performance. The findings contribute to the growing body of knowledge on the benefits of prebiotics (0.2%, PRI-A-FERM) in animal nutrition and highlight the potential for their practical application in enhancing poultry production systems. Further research is warranted to elucidate the underlying mechanisms and optimize prebiotic utilization for improved broiler health and productivity. [ABSTRACT FROM AUTHOR]

This experiment was carried out to investigate the effects of reduced dietary calcium (Ca) and non-phytatephosphorus (NPP) levels at 2:1 constant ratio on performance, carcase parameters and bone mineralization of Ross-308 broilers. A total of 11400 one-day-old chicks were randomly allocated to five dietary treatments with twelve replicates and were fed starter diets including either recommended (0.96 and 0.48 % Ca and NPP respectivelycontrol treatment, T1) or a 6.25% lower level of both Ca and NPP according to breeder's recommendations during starter period (SP). After SP, T1 continued to be provided through diets containing 0.87 and 0.78 % Ca for grower (GP) and finisher periods (FP), respectively, while 6.25 % reduced group was divided into 4 dietary treatments regarding extent of decrease in Ca and NPP levels and provided by diets containing 0.79;0.65 (T2), 0.79;0.60 (T3), 0.75;0.65 (T4), and 0.75;0.60 (T5) % Ca for GP and FP, respectively. After SP, moderate and even substantial reduction of Ca and NPP significantly decreased feed intake (FI) (quadratic, P<0.05), but obtained similar body weight gain (BWG) and FCR compared to the control (P>0.05). On the other hand, reduced dietary Ca through T1 to T5 significantly decreased the total Ca and NPP intake of broilers (linear and quadratic, P<0.01), and accompanied to significant linear and quadratic relationship between Ca intake and FCR and BWG respectively. It can be concluded that reducing Ca level down to 0.75 and 0.60 % in GP and FP, respectively are possible without compromising the growth performance and bone mineralization of modern broilers. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine how different doses of phytase in diets with extruded soybean seeds and rapeseed meal affected pigs' growth performance, meat quality, bone mineralization, and fatty acid profiles. Sixty pigs were divided into three treatments by sex and body mass. Pigs were divided into starter (25 days), grower (36 days), and finisher (33 days) periods and fed with mash diets. No phytase was used in the control group diet, whereas in Phy1 and Phy2, 100 g and 400 g of phytase per ton of mixture were used, respectively. The feed conversion ratio and meat color were significantly correlated with phytase. Phytase supplementation had no effect on the growth of pigs, but total phosphorus was significantly increased in the bones and meat of the pigs. The enzyme additive reduced the C22:4 n-6 acid content in the meat, whereas other results were not significantly affected. The data suggest that the addition of phytase at a dosage of 100 g/ton to diets with extruded full-fat soya seeds and rapeseed meal can be valuable, as it reduces the FCR and increases the P content in the meat and bones. [ABSTRACT FROM AUTHOR]

Osteoporosis is characterized by impaired bone mineralization and microarchitecture. An important protective factor is a high peak bone mass (PBM), attained in the second and third decade of life. The aim of the study was to evaluate the effect of hormonal and metabolic parameters on bone mineralization in young adult female patients. A total of 111 participants qualified for the study. Bone mineral density of the lumbar spine (L1–L4) and whole skeleton was measured using dual-energy X-ray absorptiometry (DXA). Hormonal parameters were determined: the concentrations of androstendione, dihydroepiandrosterone sulphate, testosterone, sex hormone binding protein, 17-OH-progesterone, folliculotropic hormone, estradiol, thyrotropic hormone, free thyroxine and cortisol. Metabolic parameters were also examined. The study showed a statistically significant correlation between bone mineral density and estradiol concentration and a negative relationship between cortisol concentration and the bone mineral density (BMD) Z-score of the lumbar spine. Sclerostin measurements taken during this study were not related to bone mineral density. It has been shown that the concentration of the hormones tested, even within the reference range, may affect bone mineralization. We suggest observing the follow-up of the menstrual cycles, as well as analyzing the results of test patients in an annual examination system. However, each clinical case should be considered individually. The sclerostin test is currently not useful in the clinical evaluation of bone mineralization in young adult women. [ABSTRACT FROM AUTHOR]

Simple Summary: Plants store phosphorus mainly in phytate form, which is slightly digestible by pigs due to the lack of native phytase. Some thermal processes, such as extrusion and exogenous phytase additives, can reduce phytate content in the diet, but the effectivity of the enzyme in diets including processed and unprocessed legume seeds needs to be better recognized. This study aims to investigate the effect of the addition of two phytase dosages to a diet containing raw lupine seeds and full-fat extruded soya seeds on the performance of growing pigs in terms of their carcasses, pork quality, and bone mineralization. Phytase significantly improved the pigs' growth and feed utilization in the starter period and affected some meat, fat, and bone parameters. Higher phytase dosages did not improve the pigs' performance, but only increased calcium deposition in their bones. This study aims to determine how different doses of phytase in diets including extruded soya and lupine seeds affect fatteners' performance, meat quality, bone mineralization, and fatty acid profile. Sixty pigs were divided into three treatment groups. The control group was offered a diet without phytase, whereas the Phy100 and Phy400 groups were provided with 100 g and 400 g of phytase per ton of their diet, respectively. The animals from both experimental groups were characterized by a significantly (p < 0.05) higher body weight gain and lower feed efficiency in the starter period than the control group. Unfortunately, their meat had lower (p < 0.05) fat content, gluteal muscle thickness, and water-holding capacity. In the meat, a higher phosphorus content (p < 0.05) was found, and in the bones, a higher calcium (for Phy400) content was found when phytase was added to the pigs' diet. The pigs from the Phy100 group tended to have higher mean backfat thickness and C18:2 n-6 content in their fat, but lower C22:5 n-3 content, than the other groups. A higher dosage of phytase is not necessary for the diets of fatteners with extruded full-fat soya and lupin seeds. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma is a plasma cell cancer with bone destruction and is still considered an incurable disease despite advancements in its treatment. Over 90% of patients experience bone destruction during the disease's course. NIPEP-OSS has a targeted osteogenic activity with a broad safety margin. Therefore, we repurposed NIPEP-OSS for multiple myeloma bone disease (MMBD). The present study demonstrated that NIPEP-OSS delays mouse myeloma progression via bone formation in MMBD mouse models. Multiple myeloma (MM) is the second most common hematological malignancy. It is a clonal B-cell disorder characterized by the proliferation of malignant plasma cells in the bone marrow, the presence of monoclonal serum immunoglobulin, and osteolytic lesions. An increasing amount of evidence shows that the interactions of MM cells and the bone microenvironment play a significant role, suggesting that these interactions may be good targets for therapy. The osteopontin-derived collagen-binding motif-bearing peptide NIPEP-OSS stimulates biomineralization and enhances bone remodeling dynamics. Due to its unique targeted osteogenic activity with a broad safety margin, we evaluated the potential of NIPEP-OSS for anti-myeloma activity using MM bone disease (MMBD) animal models. In a 5TGM1-engrafted NSG model, the survival rates of the control and treated groups were significantly different (p = 0.0014), with median survival times of 45 and 57 days, respectively. The bioluminescence analyses showed that myeloma slowly developed in the treated mice compared to the control mice in both models. NIPEP-OSS enhanced bone formation by increasing biomineralization in the bone. We also tested NIPEP-OSS in a well-established 5TGM1-engrafted C57BL/KaLwRij model. Similar to the previous model, the median survival times of the control and treated groups were significantly different (p = 0.0057), with 46 and 63 days, respectively. In comparison with the control, an increase in p1NP was found in the treated mice. We concluded that NIPEP-OSS delays mouse myeloma progression via bone formation in MMBD mouse models. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-starch polysaccharides and phytate have been considered the most common antinutritional factors in feedstuffs, and there is no corresponding enzyme in animals. Our results showed that the multi-carbohydrase and phytase supplementation had a potent role in improving energy, amino acids, calcium, and phosphorus digestibility in fattening pigs regardless of dietary nutrient levels, thus increasing the deposition of calcium and phosphorus in bone and improving the growth rate and feed efficiency of fattening pigs. These findings have important implications for the application of multi-enzymes in fattening pigs to spare feed costs, reduce nutrient waste, and improve swine production efficiency. This study was conducted to investigate the effects of dietary multi-enzyme (multi-carbohydrase and phytase complex, MCPC) supplementation on digestibility, growth performance, bone mineralization, and carcass yield and traits in growing–finishing pigs fed diets with adequate or deficient net energy (NE), amino acids (AA), calcium (Ca) and phosphorus (P) levels. A total of 576 crossbred [Duroc × (Landrace × Yorkshire)] barrows (~25 kg) were fed one of the six diets till live weight approached 130 kg. Basal diets included a positive control (PC), negative control 1 (NC1) and 2 (NC2), while another three diets were prepared by adding MCPC to the three basal diets. The final body weight was lower (p < 0.05) in NC2 than in NC1 and PC treatments, while overall feed intake and feed-gain ratio were higher (p < 0.05) in NC1 and NC2 than in PC treatment. The NC2 treatment showed lower (p < 0.05) carcass weight but higher (p < 0.05) lean meat percentage than the PC treatment. The apparent ileal digestibility (AID) of gross energy (GE), crude protein (CP) and AA was decreased (p < 0.05) or tended (p < 0.10) to decrease in NC1 and/or NC2 diets compared with a PC diet. MCPC supplementation improved (p < 0.05) AID of Ca, P and AA (Lys, Leu, Val, Phe, Gly, Tyr and Pro), apparent total-tract digestibility (ATTD) of GE, CP, bone strength, Ca, and P retention. In conclusion, MCPC supplementation improved nutrient digestibility, bone mineralization, and growth performance of fattening pigs, regardless of the nutritional level of the basal diet. [ABSTRACT FROM AUTHOR]

Expansion of land-based systems in fish farms elevate the content of metabolic carbon dioxide (CO2) in the water. High CO2 is suggested to increase the bone mineral content in Atlantic salmon (Salmo salar, L.). Conversely, low dietary phosphorus (P) halts bone mineralization. This study examines if high CO2 can counteract reduced bone mineralization imposed by low dietary P intake. Atlantic salmon post-seawater transfer (initial weight 207.03 g) were fed diets containing 6.3 g/kg (0.5P), 9.0 g/kg (1P), or 26.8 g/kg (3P) total P for 13 weeks. Atlantic salmon from all dietary P groups were reared in seawater which was not injected with CO2 and contained a regular CO2 level (5 mg/L) or in seawater with injected CO2 thus raising the level to 20 mg/L. Atlantic salmon were analyzed for blood chemistry, bone mineral content, vertebral centra deformities, mechanical properties, bone matrix alterations, expression of bone mineralization, and P metabolism-related genes. High CO2 and high P reduced Atlantic salmon growth and feed intake. High CO2 increased bone mineralization when dietary P was low. Atlantic salmon fed with a low P diet downregulated the fgf23 expression in bone cells indicating an increased renal phosphate reabsorption. The current results suggest that reduced dietary P could be sufficient to maintain bone mineralization under conditions of elevated CO2. This opens up a possibility for lowering the dietary P content under certain farming conditions. [ABSTRACT FROM AUTHOR]