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Summary: An experiment was conducted to evaluate the effects of phytase and multicarbohydrase (MC) on growth performance, bone ash, and nutrient digestibility in broilers fed a nutritionally reduced diet. A total of 480 Cobb 500 male broilers were randomly allocated to 8 treatments with 6 replicates of 10 birds each. Experimental diets consisted of a positive control (PC); a negative control (NC) with the reduction of ME, CP, Ca, and nonphytate phosphorus by 75 kcal/kg, 1.5, 0.15, and 0.15%, respectively; NC plus phytase at 500, 1,000, or 1,500 FTU/kg as T3–T5; and further plus MC at 500 mg/kg as T6–T8. Results showed that during 0–18 d of age, feed conversion ratio (FCR) was increased (P

Summary: An experiment was conducted to evaluate high doses of phytase associated with multicarbohydrase complex in diets with a nutritional reduction on feed cost, performance, intestinal morphometry, digesta viscosity, blood and bone parameters, and carcass yield of broilers. For this purpose, 1,540 1-day-old male broiler chicks were distributed in a completely randomized design with 5 treatments, with 14 replicates and 22 birds each. The treatments consisted of the following: positive control (PC), a diet meeting the nutritional requirements without enzymes; negative control (NC), a PC diet with a reduction of 100 kcal/kg AME, 0.15% available P, 0.12% Ca, 4% digestible lysine, and 5% Na; NC diet + multicarbohydrase complex (MCC) + phytase at 3 levels (1,000, 1,500, and 2,000 FTU/kg). The results demonstrated that the use of phytase associated with MCC in nutrient-restricted diets maintained broiler performance in the prestarter phase. From 1 to 42 d, broilers fed enzyme-supplemented diets had a better performance than those receiving nutrient-restricted diets without enzymes. The different levels of phytase associated with MCC affected the serum biochemical parameters of broilers; however, these modifications did not influence bone characteristics. The mode of action of enzymes is substrate-dependent, which may have limited enzyme activity. As a result, no improvements in carcass yield or intestinal and bone parameters were observed. It is concluded that diets with nutritional reduction and addition of 1,000 FTU/kg phytase in association with MCC maintain the performance and is a feasible strategy to reduce feed cost.

Fish are largely dependent on dietary phosphorus for skeletal development and mineralization. In aquaculture, commercial diets commonly have higher phosphorus concentration than the basal requirements in most fish species to ensure growth and prevent bone mineral disorders. Excessive phosphorus in feeds is harmful for metabolism and results in an increase of wastes in farm effluents, which impact aquatic ecosystems. Previous studies have shown that depletion/excess of dietary phosphorus cause skeletal malformations and reduced/enhanced mineralization in fish. There is scarce information on dietary phosphorus requirements for optimal bone mineralization in species with different types of bone (cellular vs. acellular bone), which is particularly relevant for sustainable aquaculture. Thus, the aim of our study was to analyse the effect of dietary phosphorus concentrations on bone mineralization of turbot, a demersal acellular‐boned fish and valuable aquaculture species. Our results show that the dietary phosphorus concentration did not cause changes to the bone mineral density and the phosphate/calcium concentrations. No apparent skeletal malformations were detected. Additionally, we did not find an altered expression of genes involved in bone mineral metabolism. Taken together, our data show that the phosphorus requirements for optimum growth and bone mineralization in turbot are below those currently used commercially at least for the time period examined: 55–195 days postfertilization (dpf). [ABSTRACT FROM AUTHOR]

The mineralization level is heterogeneous in cortical bone extracellular matrix as a consequence of remodeling. Models of the effective elastic properties at the millimeter scale have been developed based on idealizations of the vascular pore network and matrix properties. Some popular models do not take into account the heterogeneity of the matrix. However, the errors on the predicted elasticity when the difference in elastic properties between osteonal and interstitial tissues is not modeled have not been quantified. This work provides an estimation of the maximum error. We compare the effective elasticity of a representative volume element (RVE) assuming (1) different elastic properties in osteonal and interstitial tissues vs. (2) average matrix properties. In order to account for the variability of bone microstructure, we use a collection of high resolution images of the pore network to build RVEs. In each RVE we assumed a constant osteonal wall thickness and we artificially varied this thickness between 35 and 140 μ m to create RVEs with different amounts of osteonal tissue. The homogenization problem was solved with a fast Fourier transform (FFT)-based numerical scheme. We found that the error depends on pore volume fraction and varies on average from 1 to 7 % depending on the assumed diameter of the osteons. The results suggest that matrix heterogeneity may be disregarded in cortical bone models in most practical cases. [ABSTRACT FROM AUTHOR]

To evaluate the effect of reduced calcium (Ca) and available P (aP) levels in starter diets on growth performance and tibia, sternum and serum characteristics, and to assay the association between Ca and P (aP) intakes and these variables, 600 one-day-old broiler chicks (Ross 308) were used in a 21-days trial. Broilers were randomly allotted to five treatments with five replicate pens. Chicks were fed on one of the five starter diets that were formulated with a 10% reduction in the Ca and aP contents, starting from the control diet and hence, named as C (0.96% Ca, 0.45% aP), L1 (0.85% Ca and 0.42% aP), L2 (0.77% Ca and 0.38% aP), L3 (0.68% Ca and 0.34% aP) and L4 (0.61% Ca and 0.31% aP). Declining dietary Ca and aP levels did not affect body weight and levels of Ca, P and alkaline phosphatase in serum, but reduced linearly feed intake, the feed conversion ratio and the bone weight and ash content. The Ca and aP intakes and Ca:aP ratio displayed a positive correlation with both tibia and sternum weights, and the mass of the bones were equally sensitive to dietary Ca and aP levels. In conclusion, the body weight of young broilers was irresponsive to changes in the skeleton when exposed to early dietary Ca and aP restrictions (up to 0.61% Ca and 0.31% aP) and the mechanostat had limits due to the association between Ca and aP intakes, and bone properties. [ABSTRACT FROM AUTHOR]

Vitamin D (Vit.D) has been well regarded as one of the essential micronutrients for several biological functions in humans, including bone structure and function. Vit.D deficiency due to various environmental, lifestyle, and genetic factors affect bone remodeling, including bone mineralization and resorption. Consequently, several changes occur in the biochemicals that are implied in bone remodeling, either directly or via secondary pathways. Intriguingly, the levels of these biomolecules are hypothesized to have a strong association with the prognosis of Vit. D deficiency (VDD) related health complications. However, the precise association of various bone turnover-derived biomolecules with VDDrelated effects are largely elusive. Thus, the in-depth understanding of specific associations of VDD and bone mineralization would establish novel bioanalytical approaches for early detection and devise alternative strategies to provide symptomatic clinical support to VDD patients. Hence this review collates the available literature to elucidate the association between bone resorption biomarkers and their relevance to VDD. [ABSTRACT FROM AUTHOR]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An experiment was conducted to evaluate high doses of phytase associated with multicarbohydrase complex in diets with a nutritional reduction on feed cost, performance, intestinal morphometry, digesta viscosity, blood and bone parameters, and carcass yield of broilers. For this purpose, 1,540 1-day-old male broiler chicks were distributed in a completely randomized design with 5 treatments, with 14 replicates and 22 birds each. The treatments consisted of the following: positive control (PC), a diet meeting the nutritional requirements without enzymes; negative control (NC), a PC diet with a reduction of 100 kcal/kg AME, 0.15% available P, 0.12% Ca, 4% digestible lysine, and 5% Na; NC diet 1 multicarbohydrase complex (MCC) 1 phytase at 3 levels (1,000, 1,500, and 2,000 FTU/kg). The results demonstrated that the use of phytase associated with MCC in nutrient-restricted diets maintained broiler performance in the prestarter phase. From 1 to 42 d, broilers fed enzyme-supplemented diets had a better performance than those receiving nutrient-restricted diets without enzymes. The different levels of phytase associated with MCC affected the serum biochemical parameters of broilers; however, these modifications did not influence bone characteristics. The mode of action of enzymes is substrate-dependent, which may have limited enzyme activity. As a result, no improvements in carcass yield or intestinal and bone parameters were observed. It is concluded that diets with nutritional reduction and addition of 1,000 FTU/kg phytase in association with MCC maintain the performance and is a feasible strategy to reduce feed cost. [ABSTRACT FROM AUTHOR]

An experiment was conducted to evaluate the effects of phytase and multicarbohydrase (MC) on growth performance, bone ash, and nutrient digestibility in broilers fed a nutritionally reduced diet. A total of 480 Cobb 500 male broilers were randomly allocated to 8 treatments with 6 replicates of 10 birds each. Experimental diets consisted of a positive control (PC); a negative control (NC) with the reduction of ME, CP, Ca, and nonphytate phosphorus by 75 kcal/kg, 1.5, 0.15, and 0.15%, respectively; NC plus phytase at 500, 1,000, or 1,500 FTU/kg as T3-T5; and further plus MC at 500 mg/kg as T6-T8. Results showed that during 0-18 d of age, feed conversion ratio (FCR) was increased (P, 0.05) in the NC group compared with the PC group; this was recovered (P, 0.05) in T5 group; BW gain (BWG) was increased (P, 0.05) in T6-T8, and FCR was decreased (P, 0.05) in T6 and T8, compared with the NC group. For bone mineralization, fat-free dry weight, weight, percentage, and concentration of tibia ash were decreased (P, 0.05) in the NC group compared with the PC group; T3-T5 increased (P, 0.05) tibia ash percentage and concentration, compared with the NC group, but only the tibia ash percentage reached to the level that of the PC group; T6-T8 increased (P, 0.05) tibia ash weight, percentage, and concentration compared with the NC group. Similarly, nitrogen retention and AMEn were decreased (P, 0.05) in the NC group and recovered in T3-T8; ileal P digestibility also was increased in T3-T8, to a greater level than that in the PC group. The results from contrasts suggested increasing phytase level with or without carbohydrase linearly increased broiler BWG, FCR, bone mineralization, N retention, and ileal P digestibility. Moreover, when combined with carbohydrase, increased phytase level in the diet linearly increased broiler energy utilization, while phytase alone showed no effect on AMEn. In conclusion, supplementation of a combination of phytase and MC could compensate the decreases in growth performance, bone ash, and nutrient digestibility caused by a nutritionally reduced diet. [ABSTRACT FROM AUTHOR]

The tunable nature of two-dimensional nanostructured Layered Double Hydroxides [LDH] and their effective intercalation ability with biomolecules make them inevitable functional hybrid materials for versatile biomedical applications. In an attempt to meet the limitations in existing bone reconstruction practice, the present work reports the synthesis of zinc and iron-based LDH [Zn-Fe LDH] and its subsequent intercalation with thymoquinone [TQ-Zn-Fe LDH] to augment osteoblastic differentiation and proliferation for accelerated bone mineralization. Structural studies depicted the polycrystalline and amorphous nature of Zn Fe LDH and TQ-Zn-Fe LDH respectively. The biocompatible nature of LDHs was proven by negative cytotoxicity, cell adhesion, and proliferation assays studied in MG-63 cell lines. Gene expression studies of the nanocomposites showed a fold change of 5–10 in osteoblastic differentiation and proliferation. However, TQ-Zn-Fe LDH treated cells showed significantly higher protein translation levels of osteogenesis markers and elevated alkaline phosphatase secretion and calcium deposition on day 21, confirming their osteogenic efficiency. Thus, acquired results speculate the osteogenic potential of thymoquinone intercalated TQ-Zn-Fe-LDH to meet the limitations in bone reconstruction practice. [Display omitted] • Thymoquinone intercalated Zn Fe LDH provides a multidirectional effect on osteogenesis. • LDH helps in the augmentation of osteoblastogenesis and inhibition of osteoclastogenesis. • Sequential expression of alkaline Phosphatase aids in maintaining the bone homeostasis. • TQ-Zn-Fe LDH aids in accelerated mineralization by enhanced calcium deposition. • The synergistic effect of Zn, Fe, and TQ makes it a promising candidate for bone regeneration. [ABSTRACT FROM AUTHOR]

The present study evaluated the individual and combined effects of coated and uncoated phytase on broiler performance, tibia characteristics, and residual phytate phosphorus (P) in manure. Two repeated studies were conducted using 240-day-old Cobb 500 by-product male broilers per trial. For each trial, birds were assigned to four treatments with four replicate battery cages per treatment (60 birds/trt) and grown for 21 days. Treatments included: (1) negative control (NC), (2) NC + 1000 phytase units (FTU) coated phytase (C), (3) NC + 1000 FTU uncoated phytase (U), and (4) NC + 500 FTU coated + 500 FTU uncoated phytase (CU). Data were analyzed with a one-way ANOVA and means were separated using Tukey’s HSD. In the pooled data for both trials, all treatments with dietary phytase had a higher body weight (BW) and feed consumption (FC) than the NC on day 21 (p < 0.05). Similarly, a six-point reduction was observed for day 1 to 21 feed conversion (FCR) for U and CU (p < 0.05). All treatments with phytase inclusion differed from the NC in every evaluated parameter for bone mineralization (p < 0.05) and had significantly lower fecal phytate P concentrations compared to the NC (p < 0.05). Overall, bird performance was essentially unaffected by phytase form, indicating that combining phytase forms does not appear to offer any advantage to the evaluated parameters from day 1 to 21.

Bone physiology is regulated by osteoblast and osteoclast activities, both involved in the bone remodeling process, through deposition and resorption mechanisms, respectively. The imbalance between these two phenomena contributes to the onset of bone diseases. Among these, osteoporosis is the most common metabolic bone disorder. The therapies currently used for its treatment include antiresorptive and anabolic agents associated with side effects. Therefore, alternative therapeutic approaches, including natural molecules such as coumarin and their derivatives, have recently shown positive results. Thus, our proposal was to investigate the effect of the coumarin derivative umbelliferon (UF) using an interesting model of human osteoblasts (hOBs) isolated from osteoporotic patients. UF significantly improved the activity of osteoporotic-patient-derived hOBs via estrogen receptor 1 (ESR1) and the downstream activation of β-catenin pathway. Additionally, hOBs were co-cultured in microgravity with human osteoclasts (hOCs) using a 3D system bioreactor, able to reproduce the bone remodeling unit in bone loss conditions in vitro. Notably, UF exerted its anabolic role by reducing the multinucleated cells. Overall, our study confirms the potential efficacy of UF in bone health, and identified, for the first time, a prospective alternative natural compound useful to prevent/treat bone loss diseases such as osteoporosis.

Alkaline phosphatase (ALP) is one of the vital phospho-ester bond cleaving biocatalysts that has inevitable significance in cellular systems, viz., early-stage osteoblast differentiation, cell integrity in tissues, bone mineralization, cancer biomarker, liver dysfunction, cellular osmotic pressure, protein folding and many more. Variation from optimal levels of ALP in intra and extracellular fluids can cause severe diseases, including death. Due to these reasons, ALP is considered as a vital biomarker for various preclinical and medical diagnosis. Fluorescence image-based diagnosis is the most widely used method, owing to its simplicity, robustness, non-invasive properties and excellent spatio-temporal resolution (up to the nM/pM level), as compared to conventional analytical techniques, such as the electroanalytical method, nuclear magnetic resonance (NMR) and high-performance liquid chromatography (HPLC). Most of the reviews reported for ALP’s recognition in the literature scarcely explain the structurally related, photophysical and biophysical parameters; and the sub-cellular localizations. Considering these facts, in order to enhance the opto-analytical parameters of fluorescence-based diagnostic materials at the cellular level, herein we have systematically documented recent developments in the opto-analytical capabilities of quencher-free probes for ALP, used in in vitro (biological buffers) to in cellulo conditions, along with in vivo models.

The present trial was designed to assess the effect of phytase, multi-strain probiotic, Saccharomyces cerevisiae, and fumaric acid on performance, nutrient digestibility, bone physical parameters and mineralization, blood constituents, bone and gut histomorphology, and duodenal phosphorus transporter genes of broiler chickens fed a decreased non-phytate phosphorus (nPP) diet for 5 weeks. A total of 480 broiler chickens were allotted to six dietary groups and eight replicates each: (1) positive control diet with recommended levels of nPP (PC; 0.48, 0.44, and 0.41% in the three feeding phases); (2) negative control diet with a decreased dietary nPP (NC; 0.28, 0.24, and 0.21% in the three feeding phases); (3) NC + 600 FTU/kg phytase (PHY); (4) NC + 0.05% multi-strain probiotic (PRO); (5) NC + 0.2% Saccharomyces cerevisiae (SC); and (6) NC + 0.2% fumaric acid. Growth performance data were recorded weekly, and blood sampling was performed at days 21 and 35 of age. Bone quality traits, gut and tibia histology, nutrient digestibility, and intestinal gene expression analyses were conducted at the end of the trial (35 days of age). Final body weight and total gain at day 35 of age of the broiler chickens fed with the PHY, PRO, and SC diets were greater (p < 0.01) than in NC, where broilers fed with the PRO and PHY diets had higher values and were similar to that of PC. There was a non-significant variation in the cumulative feed intake among the treatment groups. The PHY and PRO groups had better FCR than the PC group (p < 0.05), and FA and SC had an FCR equivalent to that of PC. The PHY and PRO broilers had greater dressing % than the NC group (p < 0.05) and even better than PC. The PHY, PRO, SC, and FA broilers had higher relative weights of spleen and bursa of Fabricius (p < 0.01) than NC. In comparison to NC, the PHY, PRO, and SC groups improved (p < 0.05) CP, CF, Ca, and P digestibility. Greater tibia breaking strength of the low nPP-supplemented groups was shown to be associated with higher tibia ash, Ca, and P concentrations (p < 0.01) and increased (p < 0.001) tibia cortical area thickness. At days 21 and 35 of age, the dietary supplements to low nPP diets reduced (p < 0.05) serum total cholesterol, triglyceride, triiodothyronine, thyroxine, glucose, and alkaline phosphatase levels, while serum Ca and P concentrations were improved (p < 0.05) compared to NC. All supplements led to enhancement (p < 0.01) in villi height and width and villi absorptive surface area when compared with NC and were even comparable to that of PC. The mRNA expression of NaP-IIb was up-regulated (p < 0.001) in the duodenum of PRO and FA broilers at day 35 of age compared with NC, and their expression levels were similar to that of PC, indicating greater P availability. It is concluded that dietary supplementation of PHY, PRO, SC, and FA to a low nPP diet was advantageous and mitigated the negative impacts of P reduction on the growth performance, health, nutrient digestibility, and bone quality of broilers.

Serum calcium isotopes (δ44/42Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ44/42Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ44/42CaSerum with bone histology are unknown. We analyzed Ca and δ44/42Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ44/42Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ44/42CaBone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ44/42CaBone was similar in the femora and ribs. At the time of sacrifice, δ44/42CaSerum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ44/42CaBone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ44/42Ca in growing rats. δ44/42CaSerum inversely correlated with markers of bone mineralization.

Despite the significant advancement in bone tissue engineering, it is still challenging to find a desired scaffold with suitable mechanical and biological properties, efficient bone formation in the defect area, and antibacterial resistivity. In this study, the zeolite (ZSM-5) scaffold was developed using the space holder method, and a novel vancomycin-loaded alginate coating was developed on it to promote their characteristics. Our results demonstrated the importance of alginate coating on the microstructure, mechanical, and cellular properties of the ZSM-5 scaffold. For instance, a three-fold increase in the compressive strength of coated scaffolds was observed compared to the uncoated ZSM-5. After the incorporation of vancomycin into the alginate coating, the scaffold revealed significant antibacterial activity against Staphylococcus aureus (S. aureus). The inhibition zone increased to 35 mm. Resets also demonstrated 74 ± 2.5% porosity, 4.3 ± 0.07 MPa strength in compressive conditions, acceptable cellular properties (72.3 ± 0.2 (%control) cell viability) after 7 days, good cell attachment, and calcium deposition. Overall, the results revealed that this scaffold could be a great candidate for bone tissue engineering.

Summary: An experiment was conducted to evaluate the effects of dietary nonphytate phosphorus level and a novel corn-expressed phytase (GraINzyme, Agrivida Inc., Woburn, MA) supplementation on broiler growth performance and bone mineralization. Broilers were fed graded levels of nonphytate phosphorus from 0.20 to 0.44% increased by 0.06% and 4 levels of corn-expressed phytase (500; 1,500; 3,000; and 4,500 FTU/kg). Dicalcium phosphate was used as the reference for inorganic phosphorous. Increasing dietary nonphytate phosphorus level or supplementation of phytase linearly (P < 0.01) increased the bodyweight gain, feed intake, tibia fat–free dry weight, ash weight, ash percentage, and ash concentration. Feed conversion ratio was linearly (P < 0.01) improved as the dietary nonphytate phosphorus level was gradually increased. Graded nonphytate phosphorus levels were log-transformed and regressed against the bodyweight gain, tibia ash weight, ash percentage, and ash concentration for calculating the nonphytate phosphorus relative to the phytase efficacy. Both raw and standardized responses were regressed against dietary nonphytate phosphorus levels. Bodyweight gain was less sensitive than bone mineralization results. From the regression estimates using standardized responses, bodyweight gain was about 92% of tibia ash concentration in terms of sensitivity. The calculated nonphytate phosphorus relative to the equivalence for bodyweight gain, tibia ash weight, ash percentage, and ash concentration were 0.166, 0.158, 0.163, and 0.183%, respectively. Results suggest that the corn-expressed phytase is effectively released in the P form phytate and improves broiler growth performance and bone mineralization. Bone mineralization is a better indicator for the broiler response to dietary nonphytate phosphorus levels than bodyweight gain.

Objectives: Bone failure due to avascular necrosis (AVN) is a complex pathological phenomenon. Analysis of molecular changes in the bone matrix may help to shed light on the disease process and guide management. This study aimed to explore changes in bone quality and structural damage caused by sickle cell disease (SCD)induced AVN using Raman spectroscopy. Methods: A total of 10 necrotic femoral heads were obtained from seven SCD patients who underwent total hip replacements. The femoral heads were cut in half and scanned using Raman spectroscopy in correlation with preoperative magnetic resonance imaging to identify necrotic and healthy control areas. Subsequently, samples were examined to determine changes in bone mineralisation, crystallinity, carbonate content, collagen cross-linking and mineral and collagen fibril orientation. Results: Significant changes were observed in bone mineral content, mineral-to-organic content and collagen fibril orientation in necrotic compared to control areas (P ≤0.050). Conclusion: The necrotic samples displayed severe structural damage and loss of mineral and organic contents. Similar Raman signals have been reported in other metabolic bone diseases such as osteoporosis, thereby potentially supporting the use of medical treatment in AVN to promote bone quality. [ABSTRACT FROM AUTHOR]

Copyright of Der MKG-Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sturgeons and paddlefishes (Acipenseriformes) occupy the basal position of ray-finned fishes, although they have cartilaginous skeletons as in Chondrichthyes. This evolutionary status and their morphological specializations make them a research focus, but their complex genomes (polyploidy and the presence of microchromosomes) bring obstacles and challenges to molecular studies. Here, we generated the first high-quality genome assembly of the American paddlefish (Polyodon spathula) at a chromosome level. Comparative genomic analyses revealed a recent species-specific whole-genome duplication event, and extensive chromosomal changes, including head-to-head fusions of pairs of intact, large ancestral chromosomes within the paddlefish. We also provide an overview of the paddlefish SCPP (secretory calcium-binding phosphoprotein) repertoire that is responsible for tissue mineralization, demonstrating that the earliest flourishing of SCPP members occurred at least before the split between Acipenseriformes and teleosts. In summary, this genome assembly provides a genetic resource for understanding chromosomal evolution in polyploid nonteleost fishes and bone mineralization in early vertebrates. [ABSTRACT FROM AUTHOR]

Pigs (n = 192) from 64 commercial sites across 14 production facilities in the Midwest USA were used to evaluate baseline biological measurements used to determine bone mineralization in pigs. There were 3 pigs selected from each site representing: 1) a clinically normal pig, 2) a pig with evidence of clinical lameness, and 3) a pig with a history of recent low feed intake within a hospital pen (sick pig). Pigs ranged in age from nursery to market weight, with the three pigs sampled from each site representing the same phase of production. For each pig, blood, urine, and the right and left metacarpal, fibula, 2nd rib, and 10th rib were collected and analyzed. Serum was analyzed for Ca, P, and 25(OH)D3 as part of the serum chemistry profile. and. Each bone was measured for bone density and ash (non-defatted and defatted methods). Bone density was measured on each bone based on Archimedes principle. For defatted bone ash, all bones were cleaned of tissue and then placed in Soxhlet extractors containing petroleum ether for 7 days as a means of removing water and fat. Bones were then dried at 105°C for 7 days and then ashed in a muffle furnace at 600°C for 24 h. Healthy pigs had increased (P < 0.05) serum calcium and 25OHD3 compared with sick pigs, with lame pigs intermediate (Table). Healthy pigs also had increased (P < 0.05) serum phosphorus compared with sick and lame pigs, with no differences between the sick and lame pigs. For defatted bone ash and bone density, there was a pig type × bone interaction (P < 0.001). There were no differences between pig types for the fibulas, 2nd rib, and 10th rib, but metacarpals from healthy pigs had greater bone ash compared with sick pigs, with lame pigs intermediate. For bone density, healthy and lame pigs had greater (P < 0.05) bone density than sick pigs for the metacarpals and fibulas, with no difference observed for the ribs. In summary, there appear to be differences in serum analysis between a healthy, lame, and sick pig. Differences in bone mineralization between pig types were observed in the metacarpal and fibula, but not ribs. The metacarpal appears to be the most sensitive bone to detect differences in bone mineralization between pig types. There was also considerable range in values within pig type across production sites. [ABSTRACT FROM AUTHOR]

Pigs (n = 350; initial body weight = 11.9 ± 0.56 kg) were used to evaluate the effects of different bones and analytical methods on the assessment of rib bone mineralization response to dietary P and vitamin D in nursery pigs. Currently, there is little information available describing the effect of rib location (2nd through 10th) on measures of bone mineralization including density and ash. Pens of pigs (5 pigs/pen) were randomized to 6 dietary treatments in a randomized complete block design with 10 pens/treatment. Pens of pigs were assigned dietary treatments consisting of: 1) P at 0.19% STTD P (deficient); 2) P at 0.33% STTD P (NRC requirement) using monocalcium phosphate; 3) P at 0.33% STTD P using monocalcium phosphate and phytase; 4) P at 0.44% STTD P (industry level) using monocalcium phosphate, phytase, no vitamin D; 5) diet 4 with vitamin D (1,653 IU/kg), and 6) diet 5 with additional 2,000 IU/kg 25(OH)D3 (HyD). After feeding diets for 28-days, eight pigs/treatment were harvested for bone analysis. The 2nd, 3rd, 5th, 7th, and 10th ribs were collected from each pig and analyzed for bone density and non-defatted bone ash. All bones were cleaned of tissue and then dried at 105°C for 7 d and then ashed in a muffle furnace at 600°C for 24 h. Bone density was measured on each bone based on Archimedes principle. There was no interaction between bone and dietary treatment for bone density and non-defatted bone ash (P > 0.05; Table). Therefore, interpretation of results will focus on the effect of bone and treatment on measures of mineralization. Pigs fed deficient P (0.19%) had less bone density and ash percent compared with treatments fed NRC and industry levels of P. For bone density, there was a significant main effect of bone (P = 0.001), with the 10th rib having greater bone density than all other treatments and the 3rd rib having greater bone density than the 5th rib. Bone density of the 2nd and 7th ribs did not differ (P >0.05) from either the 3rd or 5th ribs. For non-defat bone ash, 10th rib had the greatest (P < 0.05) bone ash, followed by the 2nd rib which was greater (P < 0.05) than the 3rd rib, with the 5th and 7th ribs having the least non-defat bone ash percent. In summary, bone density and ash responses varied depending on the bone being measured. When measuring all of the bones, the 10th rib has the greatest value for bone density and bone ash percent, while the 5th rib has the least value for both bone density and bone ash percent compared with the rest of the bones analyzed. These results can help guide diagnostic investigations and aid in comparing results across different bones used to measure bone mineralization. [ABSTRACT FROM AUTHOR]

The goal of this research was to assess cyclic heat stress on gut permeability, bone mineralization, and meat quality in chickens. Two separate trials were directed. 320 day-of-hatch Cobb 500 male chicks were randomly assigned to four thermoneutral (TN) and four cyclic heat stress (HS) chambers with two pens each, providing eight replicates per treatment in each trial (n = 20 chicks/replicate). Environmental conditions in the TN group were established to simulate commercial production settings. Heat stress chickens were exposed to cyclic HS at 35 °C for 12 h/day from days 7–42. Performance parameters, intestinal permeability, bone parameters, meat quality, and leukocyte proportions were estimated. There was a significant (p < 0.05) reduction in body weight (BW), BW gain, and feed intake, but the feed conversion ratio increased in chickens under cyclic HS. Moreover, HS chickens had a significantly higher gut permeability, monocyte and basophil levels, but less bone mineralization than TN chickens. Nevertheless, the TN group had significant increases in breast yield, woody breast, and white striping in breast fillets compared to HS. These results present an alternative model to our previously published continuous HS model to better reflect commercial conditions to evaluate commercially available nutraceuticals or products with claims of reducing the severity of heat stress.

Increasing the demand for bone substitutes in the management of bone fractures, including osteoporotic fractures, makes bone tissue engineering (BTE) an ideal strategy for solving the constant shortage of bone grafts. Electrospun-based scaffolds have gained popularity in BTE because of their unique features, such as high porosity, a large surface-area-to-volume ratio, and their structural similarity to the native bone extracellular matrix (ECM). To imitate native bone mineralization through which bone minerals are deposited onto the bone matrix, a simple but robust post-treatment using a simulated body fluid (SBF) has been employed, thereby improving the osteogenic potential of these synthetic bone grafts. This study highlights recent electrospinning technologies that are helpful in creating more bone-like scaffolds, and addresses the progress of SBF development. Biomineralized electrospun bone scaffolds are also reviewed, based on the importance of bone mineralization in bone regeneration. This review summarizes the potential of SBF treatments for conferring the biphasic features of native bone ECM architectures onto electrospun-based bone scaffolds.

Bone loss is among the most frequent changes seen in astronauts during space missions. Although weightlessness is known to cause high bone resorption and a rapid decrease in bone minerals and calcium, the underlying mechanisms are not yet fully understood. In our work, we investigated the influence of random positioning machine (RPM) exposure on the mineralization process in the SAOS-2 cell line, in osteogenic and non-osteogenic conditions, by examining changes in their mineralizing capacity and in the expression of PTX3, a positive regulator of bone mineralization. We analyzed cell viability by MTS assay and the mineralization process after staining with Toluidine Blue and Alizarin Red, while PTX3 expression was investigated by immunocytochemistry and western blotting analysis. Our results showed that RPM exposure increased cells’ viability and improved their mineralizing competence when not treated with osteogenic cocktail. In contrast, in osteogenic conditions, cells exposed to RPM showed a reduction in the presence of calcification-like structures, mineral deposits and PTX3 expression, suggesting that the effects of RPM exposure on mineralizing matrix deposition depend on the presence of osteogenic factors in the culture medium. Further studies will be needed to clarify the role of potential mineralization markers in the cellular response to the simulated biological effects of microgravity, paving the way for a new approach to treating osteoporosis in astronauts exposed to spaceflight.

The standard of dietary non-phytate phosphorus (NPP) requirement is important for geese production. However, limited reports remain an obstacle to the NPP requirement of geese. We aimed to evaluate the NPP requirement in geese based on the effects of NPP levels on growth performance, serum variables, and bone characteristics in 1–28-day-old geese. One-day-old male Jiangnan White Geese (n = 360) were randomly divided into five groups. Five corn-soybean diets were used in these groups, with NPP levels at 0.18%, 0.28%, 0.39%, 0.47%, 0.59% in the feed, respectively. The average body weight, serum phosphorus (P) content, tibia strength, tibia P content, and femoral skim weight were significantly reduced, by 0.18%, compared with 0.28–0.59%. These variables had significant linear fit (p < 0.001) between the levels of 0.18% and 0.58%. The estimated requirement of NPP for goslings is between 0.28% and 0.35%, based on the broken-line model, using the above indicators. In conclusion, the dietary NPP requirement for 1–28-day-old geese should be no less than 0.35% to ensure normal growth performance and bone development, based on body weight gain, serum P content, and skeletal variables.

Superoxide dismutase 3 (SOD3) is an extracellular protein with the capacity to convert superoxide into hydrogen peroxide, an important secondary messenger in redox regulation. To investigate the utility of zebrafish in functional studies of SOD3 and its relevance for redox regulation, we have characterized the zebrafish orthologues; Sod3a and Sod3b. Our analyses show that both recombinant Sod3a and Sod3b express SOD activity, however, only Sod3b is able to bind heparin. Furthermore, RT-PCR analyses reveal that sod3a and sod3b are expressed in zebrafish embryos and are present primarily in separate organs in adult zebrafish, suggesting distinct functions in vivo. Surprisingly, both RT-PCR and whole mount in situ hybridization showed specific expression of sod3b in skeletal tissue. To further investigate this observation, we compared femoral bone obtained from wild-type and SOD3−/− mice to determine whether a functional difference was apparent in healthy adult mice. Here we report, that bone from SOD3−/− mice is less mineralized and characterized by significant reduction of cortical and trabecular thickness in addition to reduced mechanical strength. These analyses show that SOD3 plays a hitherto unappreciated role in bone development and homeostasis. Image 1 • Sod3a and Sod3b from zebrafish express SOD activity while only Sod3b bind heparin. • Sod3a and Sod3b are expressed in separate and distinct tissues in adult zebrafish. • Sod3b is exclusively expressed in skeletal tissues. • Femoral bone from female SOD3−/− mice are less mineralized. • The mechanical strength of bone from female SOD3−/− mice is significantly reduced. [ABSTRACT FROM AUTHOR]

Featured Application: The evaluation of the behavior of cultured cells on substrates with controlled topographies can contribute significantly to the optimization of biomaterials for bioengineering, due to the fact that cells are able to recognize topographies at different length scales and can be influenced by them. This review aims to bring together studies in the field that identify important molecular factors involved in this mechanism. In the case of osteoblasts, specific surface topographies of biomaterials used as bone grafts could lead to a fast recovery of bone defects associated with expected tissue homeostasis. In this review we have brought up the present knowledge on the interaction of osteoblasts with different substrates and we expect that its content can help in the future design of the next generation of materials for bone engineering. Bone is a specialized tissue formed by different cell types and a multiscale, complex mineralized matrix. The architecture and the surface chemistry of this microenvironment can be factors of considerable influence on cell biology, and can affect cell proliferation, commitment to differentiation, gene expression, matrix production and/or composition. It has been shown that osteoblasts encounter natural motifs in vivo, with various topographies (shapes, sizes, organization), and that cell cultures on flat surfaces do not reflect the total potential of the tissue. Therefore, studies investigating the role of topographies on cell behavior are important in order to better understand the interaction between cells and surfaces, to improve osseointegration processes in vivo between tissues and biomaterials, and to find a better topographic surface to enhance bone repair. In this review, we evaluate the main available data about surface topographies, techniques for topographies' production, mechanical signal transduction from surfaces to cells and the impact of cell–surface interactions on osteoblasts or preosteoblasts' behavior. [ABSTRACT FROM AUTHOR]

Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone‐like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx‐Cre:FNDC5/irisin KO mice, in which FNDC5/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early‐stage to adulthood. Our phenotypical analysis exhibited decreased osteoblast‐related gene expression and increased osteoclast‐related gene expression in bone tissues, and reduced adipose tissue browning due to bone‐born irisin deletion. By harvesting and culturing MSCs from the knockout mice, we found that osteoblastogenesis was inhibited and osteoclastogenesis was increased. By using irisin stimulated wildtype primary cells as a gain‐of‐function model, we further revealed the effects and mechanisms of irisin on promoting osteogenesis and inhibiting osteoclastogenesis in vitro. In addition, positive effects of exercise, including bone strength enhancement and body weight loss were remarkably weakened due to irisin deficiency. Interestingly, these changes can be rescued by supplemental administration of recombinant irisin during exercise. Our study indicates that irisin plays an important role in bone metabolism and the crosstalk between bone and adipose tissue. Irisin represents a potential molecule for the prevention and treatment of bone metabolic diseases. [ABSTRACT FROM AUTHOR]

Bone mineralization is an orchestrated process by which mineral crystals are deposited by osteoblasts; however, the detailed mechanisms remain to be elucidated. The presence of P2X7 receptor (P2X7R) in immature and mature bone cells is well established, but contrasting evidence on its role in osteogenic differentiation and deposition of calcified bone matrix remains. To clarify these controversies in the present study, we investigated P2X7R participation in bone maturation. We demonstrated that the P2X7R is expressed and functional in human primary osteoblasts, and identified in the P2RX7 promoter several binding sites for transcription factors involved in bone mineralization. Of particular interest was the finding that P2X7R expression is enhanced by nuclear factor of activated T cells cytoplasmic 1 (NFATc1) overexpression, and accordingly, NFATc1 is recruited at the P2RX7 gene promoter in SaOS2 osteoblastic‐like cells. In conclusion, our data provide further insights into the regulation of P2X7R expression and support the development of drugs targeting this receptor for the therapy of bone diseases. [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., Competing Interests: JPF reported receiving personal fees from Apomedica Pharmazeutische Produkte GmbH as employee.The authors have no conflict of interest to declare., (© 2024 The Authors.)

Introduction: Reducing the healing period after surgical placement of dental implants can facilitate the loading of dental prostheses., Aim: The aim is to compare the osteogenic potential of unmodified titanium disks with titanium disks that were surface-modified or hydrogel-coated., Materials and Methodology: One hundred eight titanium disks (Ø6 × 2-mm) were divided into three groups: (1) unmodified titanium as control (Ti-C); (2) sandblasted and acid-etched (Ti-SLA), and (3) coated with tamarind kernel polysaccharide hydrogel grafted with acrylic acid (Ti-TKP-AA). The osteogenic potential and cytotoxic effect of various groups of titanium were compared using human osteoblasts Saos-2. The surface topography of the titanium disks and morphology of osteoblasts grown on disks were investigated by scanning electron microscopy (n = 3). Cell attachment to the disks and actin expression intensity were investigated by confocal imaging (n = 3). Cytotoxicity was quantified by cell viability assay (n = 9). Osteoblast maturation was determined by alkaline phosphatase assay (n = 9). Cell mineralization was quantified by Alizarin red staining (n = 9). One-way analysis of variance followed by Tukey's multiple comparisons test was used for intergroup comparisons ( α = 0.05)., Results: The surface modifications on Ti-SLA and Ti-TKP-AA support better morphology and proliferation of osteoblasts than Ti-C (P< 0.001) and significantly higher levels of actin cytoskeleton accumulation (P< 0.0001). Ti-TKP-AA showed a significantly higher maturation rate than Ti-C (P< 0.001). Ti-TKP-AA showed > twofold increased mineralization than Ti-C and Ti-SLA (P< 0.001)., Conclusions: TKP-AA hydrogel-coated titanium promotes faster osteoblast proliferation, maturation, and mineralization than SLA-treated or untreated titanium. These advantages can be explored for achieving early osseointegration and prosthetic loading of titanium dental implants., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Majhi et al.)

Background: Children's interstitial lung disease (chILD) is a rare and potentially life-threatening condition. For many chILD conditions, systemic corticosteroids (sCCS) are considered the primary treatment despite a broad spectrum of potential side effects., Aim: We aimed to determine the long-term effects of sCCS treatment on growth, bone mineral density (BMD), and body composition after chILD., Materials and Methods: This descriptive cross-sectional single-center study included patients diagnosed with chILD before the age of 18 years treated with sCCS in the period 1998-2020. Dual-energy X-ray absorptiometry, anthropometric measurements, bone age determination, and blood tests were performed in 53 (55% males) of 89 eligible patients., Results: Median (range) age was 19.3 (6.4;30.7 years). Participants received a median (range) cumulative sCCS dose of 1144 (135; 6178) mg over a 2.0 (0.1; 13.8) years period and latest dose was administered 11.7 (1.2; 19.6) years before follow-up. Mean delta height (height standard deviation scores [SDS] - target height SDS) was reduced at sCCS treatment initiation (mean: -0.55, 95% confidence interval [CI]: -0.91; -0.20, p < .005) and at sCCS treatment cessation (mean: -0.86, 95% CI:-1.22; -0.51, p < .001), but normalized in the majority at follow-up (mean: -0.29, 95% CI:-0.61; 0.03, p = .07). Mean (SD) BMD z-score for the spine and whole body was -0.34 (1.06) and 0.52 (1.13), with no significant correlation to sCCS dose. Excess body fat (>30% in females, >25% in males) was found in 58% of patients., Conclusion: Long-term treatment with sCCS did not cause significant long-term reduction of height but showed subtle effects on fat mass percentage and BMD. Given the severity of chILD, the observed long-term effects of sCCS on growth and BMD appear acceptable., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

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 (ZnSO 4 ·7H 2 O), 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 ., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Md. Amzad Hossain reports financial support was provided by University Grants Commission of Bangladesh. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

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.

Introduction: Bone marrow lesions (BMLs) are frequently identified by MRI in the subchondral bone in knee osteoarthritis (KOA). BMLs are known to be closely associated with joint pain, loss of the cartilage and structural changes in the subchondral trabecular bone (SCTB). Despite this, understanding of the nature of BMLs at the trabecular tissue level is incomplete. Thus, we used Raman microspectroscopy to examine the biochemical properties of SCTB from KOA patients with presence or absence of BMLs (OA-BML, OA No-BML; respectively), in comparison with age-matched cadaveric non-symptomatic controls (Non-OA CTL). Methods: Tibial plateau (TP) specimens were collected from 19 KOA arthroplasty patients (6-Male, 13-Female; aged 56–74 years). BMLs were identified ex-vivo by MRI, using PDFS- and T1-weighted sequences. The KOA specimens were then categorized into an OA-BML group (n = 12; containing a BML within the medial condyle only) and an OA No-BML group (n = 7; with no BMLs identified in the TP). The control (CTL) group consisted of Non-OA cadaveric TP samples with no BMLs and no macroscopic or microscopic evidence of OA-related changes (n = 8; 5-Male, 3-Female; aged 44–80 years). Confocal Raman microspectroscopy, with high spatial resolution, was used to quantify the biochemical properties of SCTB tissue of both the medial and the lateral condyle in each group. Results: The ratios of peak intensity and integrated area of bone matrix mineral (Phosphate (v1), Phosphate (v2) and Phosphate (v4)), to surrogates of the organic phase of bone matrix (Amide I, Proline and Amide III), were calculated. Within the medial compartment, the mineral:organic matrix ratios were significantly lower for OA-BML, compared to Non-OA CTL. These ratios were also significantly lower for the OA-BML medial compartment, compared to the OA-BML lateral compartment. There were no group or compartmental differences for Carbonate:Phosphate (v1, v2 and v4), Amide III (α-helix):Amide III (random-coil), Hydroxyproline:Proline, or Crystallinity. Conclusion: As measured by Raman microspectroscopy, SCTB tissue in BML zones in KOA is significantly less mineralized than the corresponding zones in individuals without OA. These data are consistent with those obtained using other methods (e.g. Fourier transform infrared spectroscopy; FTIR) and with the increased rate of bone remodeling observed in BML zones. Reduced mineralization may change the biomechanical properties of the trabecular bone in BMLs and the mechanical interaction between subchondral bone and its overlying cartilage, with potential implications for the development and progression of OA.

Sasigarn A Bowden,1 Brian L Foster2 1Division of Endocrinology, Department of Pediatrics, Nationwide Children’s Hospital/The Ohio State University College of Medicine, Columbus, OH 43205, USA; 2Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH 43205, USA Abstract: Hypophosphatasia (HPP) is a multi-systemic metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the mineralization-associated enzyme, tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by defective bone and dental mineralization, leading to skeletal abnormalities with complications resulting in significant morbidity and mortality. Management of HPP has been limited to supportive care until the introduction of a recently approved enzyme replacement therapy employing bone-targeted recombinant human TNSALP, asfotase alfa (AA). This new therapy has been transformative as it improves survival in severely affected infants, and overall quality of life in children and adults with HPP. This review provides an overview of HPP, focusing on important steps in the development of AA enzyme replacement therapy, including the drug design, preclinical studies in the HPP mouse model, and outcomes from clinical trials and case report publications to date, with special attention given to response to therapy of skeletal manifestations, biochemical features, and other clinical manifestations. The limitations, adverse effects, and outcomes of AA are outlined and the place in therapy for individuals with HPP is discussed. Keywords: alkaline phosphatase, bone mineralization, rickets, osteomalacia, teeth, enzyme replacement therapy, inorganic pyrophosphate

A calcium deficiency is detected in more than 80% of children. This is the result of inadequate consumption of milk and dairy products which are the main food sources of calcium. There is a correlation between deficiency of calcium intake with food in childhood and the risk of osteopenia and osteoporosis in subsequent life periods. With insufficient exogenous intake of calcium, its concentration in the blood decreases which stimulates bone resorption. The factors that further limit the consumption of dairy products are lactase deficiency and cow's milk protein allergy. In order to ensure the intake of the necessary amount of calcium, it is advisable to use vitaminmineral complexes in children that contain not only a sufficient amount of calcium and vitamin D but also other micronutrients required for bone formation.

The aim of this study was to investigate the effects of olive leaf and marigold extracts on the apparent total tract digestibility (ATTD) of the principal nutrients and energy, as well as on mineral utilization (Ca, P, Mg, Mn, Fe, Cu and Zn) in relation to bone characteristics in broilers fed walnut- or linseed oil-supplemented diets. Thirty-six 12-day-old commercial broilers Ross 308 were reared in metabolic cages, assigned to one of the six dietary treatments (3 × 2 factorial design): three supplements (not supplemented, olive leaf extract, or marigold extract), and two oils (walnut or linseed oil). The results showed that the marigold extract reduced Zn and P balances and tended to lower the balance of ash and Mg, and the ATTD of Zn and Mg. Diets with linseed oil increased the ATTD of acid detergent fiber and reduced the ATTD of the organic residue and Cu. No differences in the bone characteristics of tibia were observed between treatments. These results indicated that the inclusion of marigold extract had a negative effect on the Zn and P balance, and that neither extract had any major effect on the digestion and utilization of energy and other investigated nutrients, or on bone mineralization, irrespective of the oil source included in the diet.

: The relationship between exclusive enteral nutrition (EEN) and bone status is poorly defined in pediatric Crohn disease (CD). : The aim of this study was to investigate the impact of EEN on body composition, nutritional status, and bone mineral density (BMD) in an incident CD cohort. : 18 newly diagnosed CD children starting EEN for 8 weeks were prospectively enrolled and evaluated at baseline and after 8 (T8), 26 (T26) and 52 weeks (T52) from diagnosis. The Fat Free Mass (FFM) and the Resting Energy Expenditure (REE) were measured through Bioelectrical Impedance (BIA) and the BMD was assessed by dual-energy X-ray (DXA). We compared DXA data of IBD patients to the data obtained in 15 healthy controls. : CD children had a significant lower BMD compared to healthy control both at baseline (p <0.0001), and after EEN therapy at T52 (p =0.0004); although at this latest time point CD children had a significant increase of BMD compared to baseline (p =0.0015). The BIA analysis showed a significant increase at T26 and T52 of FFM and REE. T52. FFM measured by BIA and BMD measured by DXA were significantly correlated. : EEN improves nutritional status and bone mineral composition. [ABSTRACT FROM AUTHOR]

• Vitamin K is a key cofactor for the activation of proteins. • CKD corresponds to an unique condition of vitamin K deficiency. • Vitamin K deficiency in CKD is associated with calcification and bone derangements. • Clinical data suggest that a patient's vitamin K status can be modulated. Vitamin K is a key cofactor for the activation of proteins involved in blood coagulation, apoptosis, bone mineralization regulation, and vessel health. Scientific evidence shows an important role of activated osteocalcin and matrix-Gla protein in bone and vessels, markedly affected along the course of chronic kidney disease (CKD). In fact, CKD corresponds to an unique condition of vitamin K deficiency caused by dietary restriction, intestinal dysfunction, and impaired vitamin K recycling. Clinical data suggest that vitamin K status can be modulated and this prompts us to speculate whether patients with CKD might benefit from vitamin K supplementation. However, as important as whether the improvement in vitamin K status would be able to result in better bone quality, less vascular calcification, and lower mortality rates, several issues need to be clarified. These include better standardized methods for measuring vitamin K levels, and definition of the optimal concentration range for supplementation in different subgroups. Here, we review the literature data concerning the impact of vitamin K deficiency and supplementation on CKD-associated mineral and bone disorders (CKD-MBD). We present and discuss the available evidence from basic science and clinical studies, and highlight perspectives for further research. [ABSTRACT FROM AUTHOR]

This study investigated the influence of meat and bone meal (MBM), phytase, and antibiotics (AB) on the performance, intestinal pH, ileal digestibility, cecal microbiota, and tibial mineralization in Ross 308 broilers challenged with necrotic enteritis (NE). A total of 672-day-old male Ross 308 chicks were allocated to 8 treatments with 6 replicate pens, with 14 birds each. The study employed a 2 × 2 × 2 factorial arrangement of treatments: MBM (no or yes), AB (no or yes, zinc bacitracin + salinomycin), and phytase level (500 or 1,500 FTU/kg; both using 500 matrix recommendations). Diets were based on wheat–soybean meal–canola meal. All birds were challenged with Eimeria spp on day 9 and Clostridium perfringens (C. perfringens) strain EHE-NE18 on day 14 and day 15. On day 21 (postchallenge), birds fed MBM had reduced weight gain (WG; P < 0.05) relative to without MBM. A 2-way phytase × AB interaction for WG on day 14 (P < 0.001) and day 21 (P < 0.001) and feed conversion ratio on day 21 (P < 0.001) and day 42 (P < 0.01) indicated positive effects of high phytase on bird performance in the presence of AB. On day 42, a 3-way MBM × phytase × AB interaction (P < 0.01) was observed for WG, showing high phytase increased WG with AB, relative to the birds without AB in the presence of MBM. A 2-way MBM × phytase interaction (P < 0.01) was observed for apparent ileal digestibility of Ca and P on day 16, whereby there was a notable reduction in Ca and P digestibility in birds fed MBM-free diets and a low phytase level, but with the high phytase level, Ca and P digestibility was not influenced by MBM. In conclusion, in NE challenged birds, high phytase has a beneficial effect on leg health and mineral utilization to the extent that it can replace MBM and has beneficial effects on bird performance in the presence of AB. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the effects of different levels of phytase in diets with varying amounts of phytate on live performance and bone characteristics of broiler chickens at 21 D. The treatments consisted of a 3 3 5 factorial arrangement, with 3 levels of phytate, high (HP), medium (MP), and low (LP), and 5 diets consisting of a positive control (PC); negative control (NC, with a reduction of 0.15% of calcium [Ca] and 0.15% of phosphorus [P]), and NC diet plus 0, 500, 1,000, or 1,500 FTU kg21 of phytase. Feed intake peaked with supplementation of 1,051 FTU kg21 phytase to the LP diets. Bone ash of broilers receiving LP showed a maximum response at 1,101 FTU kg21. Birds receiving the NC diet had a larger hypertrophic cartilage zone (P, 0.05) than those receiving the PC diet. Serum Ca and P of birds receiving the NC treatment and LP diet were lower than those in broilers fed with the MP and HP diets. Broilers in the NC plus 500 FYT kg21 treatments had lower tibia P levels than those in the PC treatment; also, broilers receiving HP diets had a higher tibia Ca content than those receiving LP diets (P, 0.05). In general, bone P of birds fed with diets containing HP was higher than that of birds on a LP or MP diet (P, 0.05). The use of 1,101 FTU kg21 resulted in better bone characteristics when fed with the lowest phytate level, and this level does not negatively affect the other parameters evaluated. [ABSTRACT FROM AUTHOR]

During human skeletal growth, bone is formed via different processes. Two of them are: new bone formation by depositing bone at the periosteal (outer) surface and bone remodeling corresponding to a local renewal of tissue. Since in remodeling formation is preceded by resorption, we hypothesize that modeling and remodeling could require radically different transport paths for ionic precursors of mineralization. While remodeling may recycle locally resorbed mineral, modeling implies the transport over large distances to the site of bone apposition. Therefore, we searched for potential differences of size, arrangement and chemical composition of mineral particles just below surfaces of modeling and remodeling sites in femur midshaft cross-sections from healthy children. These bone sites were mapped using scanning synchrotron X-ray scattering, Raman microspectroscopy, energy dispersive X-ray analysis and quantitative backscattered electron microscopy. The results show clear differences in mineral particle size and composition between the sites, which cannot be explained by a change in the rate of mineral apposition or accumulation. At periosteal modeling sites, mineral crystals are distinctly larger, display higher crystallinity and exhibit a lower calcium to phosphorus ratio and elevated Na and Mg content. The latter may originate from Mg used for phase stabilization of mineral precursors and therefore indicate different time periods for mineral transport. We conclude that the mineralization process is distinctively different between modeling and remodeling sites due to varying requirements for the transport distance and, therefore, the stability of non-crystalline ionic precursors, resulting in distinct compositions of the deposited mineral phase. In growing children new bone is formed either due to apposition of bone tissue e.g. at the outer ridge of long bones to allow growth in thickness (bone modeling), or in cavities inside the mineralized matrix when replacing tissue (bone remodeling). We demonstrate that mineral crystal shape and composition are not the same between these two sites, which is indicative of differences in mineralization precursors. We suggest that this may be due to a longer mineral transport distance to sites of new bone formation as compared to remodeling where mineral can be locally recycled. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The past decade, it has become evident that circadian rhythms within metabolically active tissues are very important for physical health. However, although shift work has also been associated with an increased risk of fractures, circadian rhythmicity has not yet been extensively studied in bone. Here, we investigated which genes are rhythmically expressed in bone, and whether circadian disruption by shifts in light‐dark cycle affects bone turnover and structure in mice. Our results demonstrate diurnal expression patterns of clock genes (Rev‐erbα, Bmal1, Per1, Per2, Cry1, Clock), as well as genes involved in osteoclastogenesis, osteoclast proliferation and function (Rankl, Opg, Ctsk), and osteocyte function (c‐Fos) in bone. Weekly alternating light‐dark cycles disrupted rhythmic clock gene expression in bone and caused a reduction in plasma levels of procollagen type 1 amino‐terminal propeptide (P1NP) and tartrate‐resistant acidic phosphatase (TRAP), suggestive of a reduced bone turnover. These effects coincided with an altered trabecular bone structure and increased cortical mineralization after 15 weeks of light‐dark cycles, which may negatively affect bone strength in the long term. Collectively, these results show that a physiological circadian rhythm is important to maintain bone health, which stresses the importance of further investigating the association between shift work and skeletal disorders. [ABSTRACT FROM AUTHOR]

Like other poultry species, Pekin ducks may develop gait abnormalities due to increased muscle growth relative to the skeletal system. Previous studies have shown that Pekin leg bones grow exponentially in terms of mineral deposition during the first 2 wk of life. Therefore, we hypothesized that a slight food restriction (FR) during that time would reduce muscle mass development sufficiently to allow the skeletal system to more fully develop. Our primary goal was to determine if FR could occur without increasing the time to market weight. To obtain this goal, ducks were provided either 65% (FR65) or 85% (FR85) of the control ducks daily feed intake. Food restricted ducks had lower (P < 0.05) body weights than controls at days 7 and 14. After day 14, when all ducks were fed ad libitum (ad libitum), food restricted ducks ate significantly (P < 0.01) more feed per day than control ducks and subsequently gained body weight at an increased rate. By day 35 there were no significant differences in body weight between FR85 and controls, however both FR groups showed reduced (P < 0.05) breast mass compared to controls. Qualitative assessment of gait also suggested that FR ducks had more uniform leg conformation and gait then did the control ducks and did not show any biological signs of reduced welfare. These data suggest that a slight FR is possible without adding time to market and this paradigm might reduce the occurrence of lameness in growing ducks. [ABSTRACT FROM AUTHOR]

Current approved medical treatments for osteoporosis reduce fracture risk to a greater degree than predicted from change in BMD in women with postmenopausal osteoporosis. We hypothesize that bone active agents improve bone strength in osteoporotic bone by altering different material properties of the bone. Eighteen-month-old female Fischer rats were ovariectomized (OVX) or sham-operated and left untreated for 60 days to induce osteopenia before they were treated with single doses of either risedronate (500 microg/kg, IV), zoledronic acid (100 microg/kg, IV), raloxifene (2 mg/kg, PO, three times per week), hPTH(1-34) (25 microg/kg, SC, three times per week), or vehicle (NS; 1 ml/kg, three times per week). Groups of animals were killed after days 60 and 180 of treatment, and either the proximal tibial metaphysis or lumbar vertebral body were studied. Bone volume and architecture were assessed by muCT and histomorphometry. Measurements of bone quality included the degree of bone mineralization (DBM), localized elastic modulus, bone turnover by histomorphometry, compression testing of the LVB, and three-point bending testing of the femur. The trabecular bone volume, DBM, elastic modulus, and compressive bone strength were all significantly lower at day 60 post-OVX (pretreatment, day 0 study) than at baseline. After 60 days of all of the bone active treatments, bone mass and material measurements agent were restored. However, after 180 days of treatment, the OVX + PTH group further increased BV/TV (+30% from day 60, p < 0.05 within group and between groups). In addition, after 180 days of treatment, there was more highly mineralized cortical and trabecular bone and increased cortical bone size and whole bone strength in OVX + PTH compared with other OVX + antiresorptives. Treatment of estrogen-deficient aged rats with either antiresorptive agents or PTH rapidly improved many aspects of bone quality including microarchitecture, bone mineralization, turnover, and bone strength. However, prolonged treatment for 180 days with PTH resulted in additional gains in bone quality and bone strength, suggesting that the maximal gains in bone strength in cortical and trabecular bone sites may require a longer treatment period with PTH.