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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]

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]

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]

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.

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.

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.

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

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]

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

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]

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]

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.

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]

Objective: Osteogenesis Imperfecta (OI) is a rare genetic disease group consisting of defects in collagen synthesis. This disease is characterized by alteration of connective tissue structure of exposed patients, usually caused by mutation of type I collagen. Altered connective tissue structure leads to low bone mineral density, defective bone structure and strength, and multiple fractures, which are usually obtained after low-impact trauma.[1] It is a rare disease that is seen in 0.5-1 per 10000 live births in general.[2] There are several types of OI, type I being the mildest form of OI, which is usually asymptomatic, sometimes with scoliosis due to compression fractures of the vertebrae in adults. Type II is the most severe form and is generally incompatible with life, while type III is the most severe form in surviving patients.[2-4] OI is inherited in an autosomal dominant manner and heterozygous mutation in one of the COL1A1 or COL1A2 genes is the cause in more than 90% of cases. [2,5] Type III constitutes 5% of all OI cases.[5] With this case report, we aimed to present the antenatal findings and clinical management of an OI type III case diagnosed during the antenatal period. Methods: Computer-based and ultrasonography records of a case of osteogenesis imperfecta who applied to the Perinatology outpatient clinic of Prof. Dr. Cemil Taşçıoğlu City Hospital at the 8th week of pregnancy were retrospectively scanned from the hospital system and the history of the ultrasonography device. Fetal ultrasonography examination was performed using Mindray Resona 7 device and its 1.2-6 MHz convex abdominal probe. Ultrasonography findings and patient history were noted. Case: A 40-year-old primagravid patient who became pregnant by in vitro fertilization first applied to our clinic for an 11-14 week ultrasound examination at 14 weeks of age. In the patient's anamnesis, it was learned that he had a brain aneurysm 2 years ago and had hypothyroidism. The result of the non-invasive prenatal test performed by the patient in an external center was reported as normal. In the ultrasound examination of the patient at the 14th week, hypomineralization was observed in the skull bones (Figure 1). It was observed that the head shape was deformed by the compression of the ultrasound probe. Osteogenesis imperfecta, hypophosphatasia and achondrogenesis were considered as the differential diagnosis in the patient. The patient was informed and called for follow-up 2 weeks later. In the ultrasound examination performed at the 16th week, hypomineralization was observed in the skull bones, the mineralization of the vertebral column was normal, shortness in all long bones, contractures in the hands and feet, and short costa were observed (Figure 2). The family was informed about amniocentesis and amniocentesis was performed. A heterozygous variant in the COL1A1 gene was detected in the fetus in wholeexome sequencing analysis, and this variant was reported as a pathogenic variant associated with Osteogenesis Imperfecta Type 3. The family decided to terminate. Termination was performed at 20 weeks (Figure 3,4). The patient, who had no bleeding or complaints after termination, was discharged with recommendations. Results: OI is a persistent connective tissue disease with autosomal dominant inheritance. OI Type III is shown as the most severe form in survivors.[2] Although there are treatment options such as pamidronate, zolidronate or risedronate in the postnatal period, these patients are faced with nearly 100 bone fractures and the necessity of many operations both during birth and until adolescence. For these reasons, the family should be informed in detail about the prognosis and possible risks in patients diagnosed with OI Type III, who were diagnosed with invasive diagnostic tests during the antenatal period, and the decision to continue or terminate the pregnancy should be made and managed together. [ABSTRACT FROM AUTHOR]

BackgroundDietary intake is widely known to play a crucial role in achieving peak bone mass among children and adolescents. Unfortunately, this information is lacking among Arab adolescents, an understudied demographic that has recently been observed to have a high prevalence of abnormal mineralization markers [low serum 25(OH)D, high serum alkaline phosphatase (ALP), low calcium (Ca) and/or inorganic phosphate (Pi)] suggestive of biochemical osteomalacia (OM, defined as any 2 of the 4 parameters). In order to fill this gap, we aimed to evaluate the associations of serum markers of biochemical OM with dietary intake of macronutrients, vitamins and trace minerals.MethodsSaudi adolescents (N = 2,938, 57.8% girls), aged 12–17 years from 60 different schools in Riyadh, Saudi Arabia were included. Dietary intake of nutrients was calculated following a semi-quantitative 24 h dietary recall over 3 weekdays and 1 weekend-day using a validated food frequency questionnaire. Compliance to reference daily intake (RDI) of macronutrients, vitamins and trace minerals were calculated. Fasting blood samples were collected and circulating levels of 25(OH)D, ALP, Ca, and Pi were analyzed.ResultsA total of 1819 (1,083 girls and 736 boys) adolescents provided the dietary recall data. Biochemical OM was identified in 175 (9.6%) participants (13.5% in girls, 3.9% in boys, p 50 nmol/L) but they exceed the RDI for dietary Pi. Interpreting these data in the light of the increased prevalence of rickets in Arab countries, food fortification to optimise vitamin D and Ca intake in Saudi adolescents should be considered.

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]

Enthesophyte formation plays a crucial role in the development of spinal ankylosis in ankylosing spondylitis (AS). We aimed to investigate the role of platelet‐derived growth factor B (PDGFB) in enthesophyte formation of AS using in vitro and in vivo models and to determine the association between PDGFB and spinal progression in AS. Serum PDGFB levels were measured in AS patients and healthy controls (HC). Human entheseal tissues attached to facet joints or spinous processes were harvested at the time of surgery and investigated for bone‐forming activity. The impact of a pharmacological agonist and antagonist of platelet‐derived growth factor B receptor (PDGFRB) were investigated respectively in curdlan‐treated SKG mice. PDGFB levels were elevated in AS sera and correlated with radiographic progression of AS in the spine. Mature osteoclasts secreting PDGFB proteins were increased in the AS group compared with HC and were observed in bony ankylosis tissues of AS. Expression of PDGFRB was significantly elevated in the spinous enthesis and facet joints of AS compared with controls. Moreover, recombinant PDGFB treatment accelerated bone mineralization of enthesis cells, which was pronounced in AS, whereas PDGFRB inhibition efficiently reduced the PDGFB‐induced bone mineralization. Also, PDGFRB inhibition attenuated the severity of arthritis and enthesophyte formation at the joints of curdlan‐treated SKG mice. This study suggests that regulating PDGFB/PDGFRB signaling could be a novel therapeutic strategy to block key pathophysiological processes of AS. © 2022 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Osteoporosis is characterized by low bone mass and elevated structural deterioration of the bone tissue, resulting in bone weakness with an increased risk of fracture. Considering biological activities of various phytochemicals extracted from apples, we herein demonstrated the potential antiosteoporotic effects of apple-derived nanovesicles (apple NVs) using osteoblastic MC3T3-E1 cells. Apple NVs significantly stimulated the growth of MC3T3-E1 cells. The cellular alkaline phosphatase (ALP) activity was significantly upregulated in the 5 μg/mL apple NVs-treated group. In addition, the concentrarion of mineralized nodules was significantly increased in the apple NVs-treated groups. Furthermore, apple NVs increased the expression of the genes and proteins associated with osteoblast growth and differentiation, such as Runx2, ALP, OPN, and BMP2/4, which further activated ERK- and JNK-related mitogen-activated protein kinase signaling. These results demonstrate that apple NVs have a potential to prevent osteoporosis by promoting osteoblastogenesis in osteoblastic MC3T3-E1 cells through regulating the BMP2/Smad1 pathways. [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate the effect of phytase and chelated minerals on performance, organs weight and bone mineralization indicators in broiler chickens. 240 male broiler chicken (Cobb 500) were evaluated in three experimental treatments (Basal diet, Basal diet + phytases and with Basal diet + chelated minerals) with 4 replicates (20 birds per replicate). The study was divided into three phases: start, growth and finisher. At the end of each phase, autopsies were performed to weigh the gastrointestinal organs and to evaluate indicators of bone mineralization of the left tibias. Significant differences (p <0.05) were found in the productive performance of chickens in favor of phytase treatment, except in feed intake (p > 0.05). Compared to control animals, the birds with phytase showed a significantly lower relative weight of the pancreas (p <0.05) and a statistically (p <0.05) greater intestine weight. Finally, at 42 days of age, statistical differences were observed in bone density (p < 0.05) and the Seedor index (p < 0.05) in favor of birds supplemented with phytase. Phytase supplementation improved the productive performance, reduced the weight of the pancreas and increased the weight of the intestine, and also increased bone mineralization, being more efficient than chelated minerals with respect to these variables. [ABSTRACT FROM AUTHOR]

Hyperthyroidism causes secondary osteoporosis through favoring bone resorption over bone formation, leading to bone loss with elevated bone fragility. Osteocytes that reside within lacunae inside the mineralized bone matrix orchestrate the process of bone remodeling and can themselves actively resorb bone upon certain stimuli. Nevertheless, the interaction between thyroid hormones and osteocytes and the impact of hyperthyroidism on osteocyte cell function are still unknown. In a preliminary study, we analyzed bones from male C57BL/6 mice with drug‐induced hyperthyroidism, which led to mild osteocytic osteolysis with 1.14‐fold larger osteocyte lacunae and by 108.33% higher tartrate‐resistant acid phosphatase (TRAP) activity in osteocytes of hyperthyroid mice compared to euthyroid mice. To test whether hyperthyroidism‐induced bone changes are reversible, we rendered male mice hyperthyroid by adding levothyroxine into their drinking water for 4 weeks, followed by a weaning period of 4 weeks with access to normal drinking water. Hyperthyroid mice displayed cortical and trabecular bone loss due to high bone turnover, which recovered with weaning. Although canalicular number and osteocyte lacunar area were similar in euthyroid, hyperthyroid and weaned mice, the number of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling (TUNEL)‐positive osteocytes was 100% lower in the weaning group compared to euthyroid mice and the osteocytic TRAP activity was eightfold higher in hyperthyroid animals. The latter, along with a 3.75% lower average mineralization around the osteocyte lacunae in trabecular bone, suggests osteocytic osteolysis activity that, however, did not result in significantly enlarged osteocyte lacunae. In conclusion, we show a recovery of bone microarchitecture and turnover after reversal of hyperthyroidism to a euthyroid state. In contrast, osteocytic osteolysis was initiated in hyperthyroidism, but its effects were not reversed after 4 weeks of weaning. Due to the vast number of osteocytes in bone, we speculate that even minor individual cell functions might contribute to altered bone quality and mineral homeostasis in the setting of hyperthyroidism‐induced bone disease. © 2022 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]

Background: "Ping-pong" fractures are a type of depressed fracture in which there is no rupture of the inner or outer table of the skull. It is produced by incomplete bone mineralization. Its appearance is frequent during neonatal and infant ages and is extremely rare outside of these age periods. The objective of this article is to present the case of a 16-year-old patient who presented a "ping-pong" fracture after a traumatic brain injury (TBI) and discuss the underlying physiopathogenesis of these types of fractures. Case Description: A 16-year-old patient presented to the emergency department with a TBI, referring headaches and nausea. Non-contrast brain computed tomography displayed a left parietal "ping-pong" fracture. Laboratory tests showed hypocalcemia, subsequently diagnosing hypoparathyroidism. The patient remained under observation for 48 h. He was managed conservatively and started on calcium carbonate and vitamin D supplements with a favorable evolution. Hospital discharge was granted with TBI discharge instructions and warning signs. Conclusion: The age of presentation of our case was atypical, according to the reported literature. When faced with a "ping-pong" fracture outside of an early age, underlying bone pathologies must be ruled out, which could potentially generate incomplete bone mineralization of the skull. [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 Background Preterm infants have a low level of bone mineralization compared to those born at term, since 80% of calcium incorporation occurs at the end of pregnancy. The purpose of the present study was to investigate the effect of reflex locomotion therapy on bone modeling and growth in preterm infants and to compare its effect with those of other Physiotherapy modalities. Methods A multicentre randomized controlled clinical trial was conducted (02/2016 – 07/2020). 106 preterm infants born at the Virgen de la Arrixaca University Clinical Hospital, the General University Hospital of Elche and the Torrecárdenas University Hospital of Almería, between 26 and 34 weeks with hemodynamic stability, complete enteral nutrition and without any metabolic, congenital, genetic, neurological or respiratory disorders were evaluated for inclusion. Infants were randomly assigned to three groups: one group received reflex locomotion therapy (EGrlt); another group received passive mobilizations with gentle joint compression (EGpmc); and the control group received massage (CG). All treatments were carried out in the neonatal units lasting one month. The main outcome measure was bone formation and resorption measured with bone biomarkers. A mixed ANOVA was used to compare the results of bone biomarkers, and anthropometric measurements. Results Infants were randomized to EGrlt (n = 38), EGpmc (n = 32), and CG (n = 36). All groups were similar in terms of gender (p = 0.891 female 47.2%), gestational age (M = 30.753, SD = 1.878, p = 0.39) and birth weight (M = 1413.45, SD = 347.36, p = 0.157). At the end of the study, significant differences were found between the groups in their interaction in bone formation, measured with osteocalcin [F (2,35) = 4.92, p = 0.013, ηp 2 = 0.043], in benefit of the EGrlt. Conclusions Reflex locomotion therapy has been effective in improving bone formation, more so than other Physiotherapy modalities. Therefore, reflex locomotion therapy could be considered one of the most effective physiotherapeutic modalities for the prevention and treatment of osteopenia of prematurity. Trial registrstion Trial retrospectively registered at ClinicalTrials.gov. First posted on 22/04/2020. Registration number: NCT04356807 .

Background. The efficacy of vitamin D3 agents for impaired growth of children of different cause was studied in the research. A positive effect on bone mineralization and calcium-phosphorus metabolism was evidenced. The treatment and prophylaxis charts using this drug for osteopenic syndrome are developed for children with hypothalamic-pituitary dwarfism, subdwarfism and dwarfism of constitutional genesis. Objective. The aim of the research is to study the effect of calcimine and vitamin D3 in cases of impaired bone mineral density in children aged 6-18 years old with growth retardation of the hypothalamic-pituitary genesis, subdwarfism and dwarfism of constitutional origin. Methods. The study involved 25 children, aged 6-18 years old with growth retardation: hypothalamic-pituitary (10 children), subdwarfism (5 children) and dwarfism of constitutional origin (10 children). The control group consisted of 20 children. The structural and functional state of bone tissue was studied using a two-photon X-ray densitometer “Lunar”. In the study of calcium-phosphorus homeostasis, the level of calcium and the level of phosphorus in the blood serum were determined. Serum alkaline phosphatase levels were also studied as a marker for bone formation. Results. In the examined children, there was a significant calcium deficiency at the level of the vertebrae L1–L4. The calcium content in L1 was 72.8%, L2 – 75.7%, L3 – 81.2%, L4 – 80.1%, which significantly differed from bone density in healthy children of a similar age and body weight. It was also revealed that in children diagnosed with growth retardation of the pituitary genesis, bone rarefaction was diagnosed in 100% of cases, while with subdwarfism and dwarfism of constitutional genesis these indicators were 43% and 24%, respectively. Conclusions. A differentiated choice of vitamin D3 treatment, depending on the degree of osteopenia in children, allows adjusting the calcium metabolism and preventing osteoporosis in children with stunted growth. Vitamin D3 in the complex treatment of osteoporosis in children with growth impairment of different genesis normalizes calcium-phosphorus homeostasis, which increases bone mineral density and, therefore, reduces osteoporotic changes by stopping leaching of calcium from bones.

Simple Summary: The eggshell provides physical protection of the internal components of the egg. Calcium, the main mineral forming eggshell, comes both directly from the diet but also from bones. Continuous bone demineralization may lead to osteoporosis and bone fractures. The main energy source in hens' diet is corn, but also grains, like wheat or rye, can be introduced. However, due to the presence of non-starch polysaccharides, which cannot be utilized by poultry, absorption of nutrients might be reduced. The enzyme xylanase, supplemented in diets improves nutrient uptake. In this study, the effect of a modern hybrid rye included in a wheat–corn diet with xylanase supplementation on eggshell and bone quality in laying hens was examined. The results showed that hybrid rye can replace corn in hens' diet without negative effects on eggshell quality or bone mechanical strength, but xylanase supplementation to these diets is recommended. The objective of this study was to evaluate whether there are negative effects of the partial replacement of white corn with rye along with xylanase supplementation on overall bone quality, eggshell mineralization, and mechanical strength in laying hens. From the 26th week of life, ISA Brown laying hens were fed either a wheat–corn diet or a diet containing 25% rye, with or without xylanase. The experimental period lasted for 25 weeks, until birds reached their 50th week of age, after which bone and eggshell quality indices were assessed. Eggshell thickness and eggshell Ca content of eggs from rye-fed hens were improved by xylanase supplementation. No differences in the mechanical properties of the eggshells were observed between treatments, except for the diet-dependent changes in egg deformation. Rye inclusion had no effect on the mechanical properties of bone. Xylanase supplementation, irrespective of the diet, had a positive effect on bone strength and increased tibia Ca content, as well as the content of several microelements. Hence, hybrid rye combined with wheat can replace 25% of corn in layer diets without compromising shell quality or bone mineral content. Xylanase supplementation in these diets is recommended since its inclusion improves both bone strength and quality. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the influence of the titanium nanotube diameter and the effect of silicon carbide (SiC) coating on the proliferation and mineralization of pre-osteoblasts on titanium nanostructured surfaces. Anodized titanium sheets with nanotube diameters of 50 and 100 nm were used. The following four groups were tested in the study: (1) non-coated 50 nm nanotubes; (2) SiC-coated 50 nm titanium nanotubes; (3) non-coated 100 nm nanotubes and (4) SiC-coated 100 nm nanotubes. The biocompatibility and cytotoxicity of pre-osteoblasts were evaluated using a CellTiter-BlueCell Viability assay after 1, 2, and 3 days. After 3 days, cells attached to the surface were observed by SEM. Pre-osteoblast mineralization was determined using Alizarin-Red staining solution after 21 days of cultivation. Data were analyzed by a Kruskal–Wallis test at a p-value of 0.05. The results evidenced biocompatibility and non-cytotoxicity of both 50 and 100 nm diameter coated and non-coated surfaces after 1, 2 and 3 days. The statistical analysis indicates a statistically significant higher cell growth at 3 days (p < 0.05). SEM images after 3 days demonstrated flattened-shaped cells without any noticeable difference in the phenotypes between different diameters or surface treatments. After 21 days of induced osteogenic differentiation, the statistical analysis indicates significantly higher osteoblast calcification on coated groups of both diameters when compared with non-coated groups (p < 0.05). Based on these results, we can conclude that the titanium nanotube diameter did not play any role on cell viability or mineralization of pre-osteoblasts on SiC-coated or non-coated titanium nanotube sheets. The SiC coating demonstrated biocompatibility and non-cytotoxicity and contributed to an increase in osteoblast mineralization on titanium nanostructured surfaces when compared to non-coated groups. [ABSTRACT FROM AUTHOR]

Globally, millions require bone replacements with the help of scaffolds to enable bone tissue regeneration. However, scaffold manufacturing techniques do not allow precise control over scaffold geometry and provide diagnostics on scaffold-cell status. Towards addressing these challenges, we studied the use of optimized 3D printing of bioresorbable scaffolds with fluorescent carbon quantum dots (CDs). These can overcome the challenges with toxic and invasive dyes used in clinical settings as probes, while promoting cellular adhesion, proliferation, and osteogenic differentiation. We developed a biodegradable polymer nanocomposite based on PLA with CDs to produce smart biomaterials. As a luminescent, biocompatible material with low toxicity, CDs allowed us to fabricate functionalized biochemical structures that were shown to enhance cell proliferation and promote cell-to-cell communication. The composites were tested in vitro in a cellular microenvironment with optimized 3D-printed scaffolds to demonstrate enhancements in cellular proliferation by 32%, bone mineralization by 8% and osteogenic differentiation by 8% with concomitant negligible cytotoxic effect. [ABSTRACT FROM AUTHOR]

Osteoporosis is defined as a universal skeletal disorder. The medicinal importance of earthworms has been known from time immemorial. The present investigation was designed to assess the antiosteoporotic efficacy of the earthworm, Allolobophora caliginosa extract (AcE) in bilaterally orchiectomized rats (OCX) to elicit the underlying in vivo mechanism. Twenty-eight male rats were divided into two groups. The first group (7 rats/group) represented sham-operated rats, while the second group (21 rats/group) underwent bilateral orchidectomy (OCX). The second group was randomly subdivided into three subgroups; OCX and A. caliginosa extract (AcE) (100 or 200 mg/kg body weight/day) treated subgroup. Administration of AcE to OCX rats increased femoral bone mineral density (BMD), bone mineral content (BMC), calcium (Ca), phosphorus (P), and calcitonin level, as compared to OCX rats. On the other hand, administration of AcE to OCX rats significantly decreased serum alkaline phosphatase (ALP) activity and parathyroid hormone (PTH) level compared to OCX rats. The present study showed that AcE is a beneficial novel natural antiresorptive agent. Its anti-osteoporotic effects may positively impact osteoblast differentiation, particularly bone mineralization, and higher osteoblast activity account for bone formation, preventing osteoporosis.

Abstract In recent years, much progress has been made in understanding the mechanisms of bone growth and development over a lifespan, including the crosstalk between muscle and bone, to achieve optimal structure and function. While there have been significant advances in understanding how to help improve and maintain bone health in normal individuals, there is limited knowledge on whether these mechanisms apply or are compromised in pathological states. X-linked hypophosphatemia (XLH) (ORPHA:89936) is a rare, heritable, renal phosphate-wasting disorder. The resultant chronic hypophosphatemia leads to progressive deterioration in musculoskeletal function, including impaired growth, rickets, and limb deformities in children, as well as lifelong osteomalacia with reduced bone quality and impaired muscle structure and function. The clinical manifestations of the disease vary both in presentation and severity in affected individuals, and many of the consequences of childhood defects persist into adulthood, causing significant morbidity that impacts physical function and quality of life. Intervention to restore phosphate levels early in life during the critical stages of skeletal development in children with XLH could optimize growth and may prevent or reduce bone deformities in childhood. A healthier bone structure, together with improved muscle function, can lead to physical activity enhancing musculoskeletal health throughout life. In adults, continued management may help to maintain the positive effects acquired from childhood treatment, thereby slowing or halting disease progression. In this review, we summarize the opinions from members of a working group with expertise in pediatrics, epidemiology, and bone, joint and muscle biology, on potential outcomes for people with XLH, who have been optimally treated from an early age and continue treatment throughout life.

Exposure to plastic-derived estrogen-mimicking endocrine-disrupting bisphenols can have a long-lasting effect on bone health. However, gestational exposure to bisphenol A (BPA) and its analogue, bisphenol S (BPS), on offspring's bone mineralization is unclear. The effects of in-utero bisphenol exposure were examined on the offspring's bone parameters. BPA and BPS (0.0, 0.4 μg/kg bw) were administered to pregnant Wistar rats via oral gavage from gestational day 4–21. Maternal exposure to BPA and BPS increased bone mineral content and density in the offspring aged 30 and 90 days (P < 0.05). Plasma analysis revealed that alkaline phosphatase, and Gla-type osteocalcin were significantly elevated in the BPS-exposed offspring (P < 0.05). The expression of BMP1 , BMP4 , and their signaling mediators SMAD1 mRNAs were decreased in BPS-exposed osteoblast SaOS-2 cells (P < 0.05). The expression of extracellular matrix proteins such as ALPL, COL1A1, DMP1, and FN1 were downregulated (P < 0.05). Bisphenol co-incubation with noggin decreased TGF-β1 expression, indicating its involvement in bone mineralization. Altered mineralization could be due to dysregulated expression of bone morphogenetic proteins and signalling mediators in the osteoblast cells. Thus, bisphenol exposure during gestation altered growth and bone mineralization in the offspring, possibly by modulating the expression of Smad-dependent BMP/TGF-β1 signalling mediators. [Display omitted] • Fetal exposure to BPS increases the offspring's whole-body bone mineral content and density, similar to BPA. • In-utero BPS exposure decreases plasma calcium and increases ALP and Gla-type osteocalcin in the offspring. • Bisphenol exposure modulates Smad-dependent BMP/TGF-β1 signaling in the SaOS-2 cells. [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 (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.

IntroductionNatural and synthetic estrogens are pollutants found in aquatic ecosystems at low concentrations reaching ng.L-1 to μg.L-1. At these concentrations, they are able to interfere with the fish endocrine system. When waterborne exposure occurs at early life stages, when blood estrogens concentrations are low, this may have significant consequences for estrogen-sensitive functions such as skeletal development.MethodsTo better understand how (xeno)estrogens may affect early head mineralization, 12 days post-hatch larvae of the European seabass Dicentrarchus labrax were experimentally exposed for 4 days to the natural estrogen estradiol E2 and to the xenoestrogen bisphenol A (BPA), both used at either regulatory concentration of water quality or a 100 times higher concentration. Head mineralization level was assessed using Alizarin red staining, together with the relative quantification of mRNA expression levels of several genes playing key roles in skeletogenesis and estrogen signaling pathways.ResultsWe showed that (xeno)estrogen exposure at early larval stage increases the expression of skeleton-associated genes: matrix proteins encoding genes (col1a2, col2a1a, col2a1b, bgp1a, bgp1b, sparc), proteolytic enzyme encoding genes (ctsk) and transcription and signaling factors (sox9a, sox9b, ihha, runx2, rankl). Although transcriptional overexpression of these genes was significant in larvae exposed to 40 ng.L-1 E2 and to 1.6 and 160 μg.L-1 BPA, increased mineralization was detected only in E2-exposed larvae, suggesting a difference in head skeleton development and remodeling in BPA-treated larvae.DiscussionOur results suggest that these phenotypic differences could be due to the implication of other estrogenic signaling pathways involving both nuclear and membrane-bound estrogen receptors (ERs and GPERs), but also estrogen-related receptors (ERRs). This study brings new insights into the regulatory mechanisms of skeletogenesis by E2 and BPA and into the effects of waterborne exposure to (xeno)estrogens on the early skeletal development of teleost fishes.

Bisphenol A (BPA) is one of the world’s most widely used plasticizer, and its hazardous impacts have been well studied. However, few studies focused on the effects of parental long-term BPA exposure on the bone development of offspring. In the present study, the bone development of offspring was studied following long-term exposure of parental zebrafish to environmentally relevant 15 and 225 µg/L BPA. The results showed that BPA increased the mortality and deformity rate of offspring and caused craniofacial deformities characterized by changes in various cartilage angles and lengths. The alizarin red and calcein staining showed that BPA could delay bone mineralization and reduce bone mass accumulation. The results of acridine orange staining indicated that BPA induced apoptosis of the skull. The degree of harm of BPA presented a dose-dependent pattern. The results of the comparative transcriptome showed that there were 380 different expression genes (DEGs) in the 15 µg/L BPA group, and 645 DEGs in the 225 µg/L BPA group. MAPK/Wnt/FoxO signaling pathway-related genes were significantly down-regulated in the BPA-exposed groups. The present study demonstrates that long-term parental BPA exposure would severely affect cartilage development and bone mineralization of fish offspring, and MAPK/Wnt/FoxO signaling pathways may be involved in this process.

Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by osteoblasts, and thereafter, bone mineral density gradually increases during secondary mineralization. Nearby extracellular phosphate ions (PO43−) flow into the vesicles via membrane transporters and enzymes located on the vesicles' membranes, while calcium ions (Ca2+), abundant in the tissue fluid, are also transported into the vesicles. The accumulation of Ca2+ and PO43− in the matrix vesicles induces crystal nucleation and growth. The calcium phosphate crystals grow radially within the vesicle, penetrate the vesicle's membrane, and continue to grow outside the vesicle, ultimately forming mineralized nodules. The mineralized nodules then attach to collagen fibrils, mineralizing them from the contact sites (i.e., collagen mineralization). Afterward, the bone mineral density gradually increases during the secondary mineralization process. The mechanisms of this phenomenon remain unclear, but osteocytes may play a key role; it is assumed that osteocytes enable the transport of Ca2+ and PO43− through the canaliculi of the osteocyte network, as well as regulate the mineralization of the surrounding bone matrix via the Phex/SIBLINGs axis. Thus, bone mineralization is biologically regulated by osteoblasts and osteocytes. [ABSTRACT FROM AUTHOR]

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