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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., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bailey and Fraser.)

Osteoporosis is a chronic bone disorder characterized by decreased bone mass, leading to brittle bones and fractures. Oxidative stress has been identified as the most profound trigger for the initiation and progression of osteoporosis. Current treatment strategies do not induce new bone formation and fail to address a high level of reactive oxygen species (ROS). Mesoporous silica nanoparticles (MSNs) have been explored in bone tissue regeneration owing to their inherent osteogenic property, but they lack antioxidant and cell adhesion properties, required in such applications. We have developed thiolated, bioactive mesoporous silica nanoparticles (MSN-SH) to address this challenge. MSNs were fabricated using the Stöber method, and 11% of the surface was functionalized post-synthesis with thiol groups using MPTMS to obtain MSN-SH. The particle size measured by the dynamic light scattering technique was found to be around 300 nm. The surface morphology was investigated using HR-TEM, and their physical and chemical properties were characterized using various spectroscopic techniques. They exhibited more than 90% antioxidant activity, neutralized ROS formed in cells, and provided protection against ROS-induced cell damage. The cell viability assay in murine osteoblast precursor cells (MC3T3) showed that MSN-SH is cell-proliferative in nature with 140% cell viability. Osteogenic potential was evaluated by measuring the ALP activities, calcium deposition, and gene expression levels of osteogenic markers, such as RUNX2, ALP, OCN, and OPN, and results revealed that MSN-SH increases calcium deposition and induces osteogenesis through upregulation of osteogenic genes and markers without the involvement of any osteogenic supplements. Besides promoting osteogenesis, MSN-SH was found to inhibit osteoclastogenesis. The nanomaterial was found to be regenerative in nature, and it stimulated migration of osteoblast cells and caused a complete wound closure within 48 h. We were able to achieve a multifunctional nanomaterial by simply modifying the surface. MSNs have been explored for bone tissue engineering/osteoporosis as a composite system incorporating metals, like gold and cerium, or as a nanocarrier loaded with growth factors or active drugs. This study offers a simple and economical method to enhance the existing properties of MSNs and impart new activities by a single-step surface modification. It can be concluded that MSN-SH holds promise as a complementary and alternate treatment for osteoporosis along with the standardized therapy.

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  μ g/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.

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.

Background: Polycystic ovary syndrome (PCOS) has reproductive and metabolic aspects that may affect bone health. Controversial results from different studies regarding the risk of fractures, bone mineral density (BMD) or bone markers led to uncertainty whether PCOS might improve or deteriorate bone health., Objective and Rationale: This study aimed to investigate the impact of PCOS on bone markers, BMD and fracture risk., Search Methods: A systematic review and a meta-analysis were carried out. PubMed, EMBASE and Cochrane databases were searched for eligible studies from 1st of January of 1990 to 9th of October of 2018. Eligible studies enrolled women older than 18 years with PCOS, which should be diagnosed according to the Rotterdam Consensus, the Androgen Excess Society, the National Institutes of Health Consensus or the International Classification of Diseases. The studies were grouped according to patient mean BMI: <27 kg/m2 or ≥27 kg/m2. The results were polled as mean difference (MD), standardized MD (SMD) and hazard ratio (HR)., Outcomes: Overall, 921 studies were retrieved, and 31 duplicated studies were removed. After screening the titles and abstracts, 80 studies were eligible for full text reading. Of those, 23 studies remained for qualitative synthesis. With the exception of one study, all studies were considered high quality based on the Newcastle-Ottawa scale (NOS; score ≥6). Meta-analysis was performed in 21 studies, with a total of 31 383 women with PCOS and 102 797 controls. Women with PCOS with BMI <27 kg/m2 had lower BMD of the total femur (MD, -0.04; 95% CI, -0.07 to 0.00; I2 = 31%; P = 0.22) and spine (MD, -0.07; 95% CI, -0.13 to -0.01; I2 = 70%; P < 0.01) when compared with the control group, whereas for women with BMI ≥27 kg/m2 no difference was observed (femur: MD, 0.02; 95% CI, -0.02 to 0.05; I2 = 20%, P = 0.29; spine: MD, 0.02; 95% CI, -0.06 to 0.05; I2 = 0%; P = 0.84). Osteocalcin was remarkably reduced in women with PCOS with BMI <27 kg/m2 (SMD, -2.68; 95% CI, -4.70 to -0.67; I2 = 98%; P < 0.01), but in women with BMI ≥27 kg/m2, there were no differences between PCOS and controls. Few studies (n = 3) addressed the incidence of bone fractures in women with PCOS. The HR for total bone fractures did not identify differences between women with PCOS and controls., Wider Implications: On the basis of the available evidence, it is possible to assume that PCOS in women with BMI <27 kg/m2 is associated with reduced BMD in the spine and femur, and decreased bone formation, as manifested by lower levels of circulating osteocalcin. These findings suggest that bone parameters in PCOS may be linked, to some extent, to adiposity. These studies included premenopausal women, who have already achieved peak bone mass. Hence, further prospective studies are necessary to clarify the existence of increased risk of fractures in women with PCOS., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Rheumatic diseases are associated with an increased fracture risk. The tissue level characteristics of the bone involvement in children have not been well elucidated. Our objectives were to describe the bone micro-architectural characteristics in children with rheumatic diseases on chronic glucocorticoids, and to determine associations between micro-architectural findings with clinical and radiological variables., Methods: Children on chronic glucocorticoids for an underlying rheumatic disease were referred for evaluation of bone fragility given the presence of vertebral compression fractures. A trans-iliac bone biopsy was performed as part of the clinical assessment. Histomorphometric analysis and quantitative backscattered electron imaging (qBSE) of the biopsy samples were undertaken., Results: Data of 15 children (14.0 ± 3.2 years) with a duration of glucocorticoid exposure of 6.2 ± 4.1 years and average prednisone dose of 14.1 ± 6.2 mg/m 2 /day were assessed. Histomorphometric analyses demonstrated significant decrease in trabecular thickness (p = 0.01), osteoid thickness (p < 0.01), osteoblast surface (p = 0.02) and increase in trabecular separation (p = 0.04) compared to published age-matched normative data. Severity of the trabecular deficit was correlated to glucocorticoid dose, height and body mass index Z score, but not bone mineral density or measures of disease activity. Using qBSE to measure bone mineralization, the subjects were shown to have a heterogeneous and hypermineralized profile, with higher cumulative glucocorticoid dose being associated with greater mineralization (p < 0.01)., Conclusions: In children with rheumatic diseases presenting with vertebral fractures, there is evidence of abnormal bone matrix mineralization and impairments of bone micro-architecture that correlate to glucocorticoid dose.

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]

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: 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]

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.

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. [ABSTRACT FROM AUTHOR]

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.

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]

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.

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.

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.

Osteoporosis (OP), characterized by decreased bone density and destruction of bone microstructure, is a common systemic bone disease in the elderly. Conventional therapies suffer from poor targeting and long-term toxicity. Engineered bacterial extracellular vesicles (BEVs) containing bioactive molecules show great potential as alternative OP therapies. Here, we developed a delivery system based on BEVs secreted probiotic Lactobacillus rhamnosus GG (LGG). Bone-targeting peptides were anchored on the LGG-EVs membranes, which endowed LGG-EVs the ability to deliver intrinsic miRNA to bone microenvironment. Bone-targeted LGG-EVs (BT-LGG-EVs) exhibited great bone targeting capability without significant toxicity. BT-LGG-EVs not only promoted osteogenic differentiation and mineralization but also inhibited the formation of osteoclasts. Furthermore, BT-LGG-EVs were demonstrated to be able to attenuate the OVX-induced osteoporotic phenotypes. Our study demonstrated that BT-LGG-EVs hold great promise for use as an innovative, safe, and effective solution for the treatment of OP. [ABSTRACT FROM AUTHOR]

PurposePhysical inactivity is deleterious to health, but it has been difficult to determine the extent to which these effects are attributable to abnormal body composition or to factors related to physical activity alone. To begin to gauge independent effects of physical activity on health risk, we matched by BMI two groups of normal-weight adolescent females, one physically active (all participants in high school sports), and one sedentary.MethodsThirty-seven sedentary and 37 physically active adolescent females (mean 15.5 yr) were matched for age and BMI percentile (mean = 58.8). Comparisons included fitness, body composition and bone mineralization (by DEXA), circulating inflammatory cytokines, growth factors, bone-turnover markers, leptin, and adiponectin.ResultsCompared with the normal-weight sedentary girls, active girls had significantly (P < 0.05) higher fitness level (peak VO2 35.5 +/- 5.2 vs 24.4 +/- 4.1 mL.kg(-1).min(-1)), lean body mass (43.2 +/- 4.4 vs 38.7 +/- 3.6 kg), bone mineralization (spinal BMD z-scores 0.04 +/- 0.88 vs -0.41 +/- 0.85), and lower percent body fat (25.4 +/- 04.6 vs 29.7 +/- 03.7%). Additionally, active girls had lower inflammatory cytokines levels (e.g., TNF-alpha 1.7 +/- 1.3 vs 2.6 +/- 2.2 pg.mL(-1)), and leptin (17.4 +/- 11.2 vs 24.7 +/- 14.7 ng.mL(-1)), and higher bone-turnover markers (e.g. osteocalcin 12.6 +/- 7.6 vs 7.8 +/- 3.0 U.L(-1)), IGFBP-3 (6416 +/- 21280 vs 4247 +/- 1082 ng.mL(-1)), and adiponectin levels (11919 +/- 3935 vs 9305 +/- 2843 ng.mL(-1)).ConclusionThe normal-weight, physically active group was fitter and had greater lean body mass, stronger bones, and lower levels of inflammatory markers than did the normal-weight, sedentary group. In adolescent girls, the choice of a lifestyle involving high school sports is characterized by a circulating mediator and body composition pattern that, if sustained, is associated with generally lower long-term risk of cardiovascular disease and osteoporosis.

Objective: To study bone mineral density (BMD) in adolescent females according to five groups of chronological age (CA), bone age (BA), and breast development stage (B), and to correlate these parameters with plasma bone biomarkers (BB). Methods: This was a cross‐sectional study performed in 101 healthy adolescent females between 10 and 20 years old. The study variables were: weight, height, body mass index (BMI), CA, B, BA, calcium intake, BMD, and BB. Osteocalcin (OC), bone alkaline phosphatase (BAP), and C‐terminal telopeptide (S‐CTx) were evaluated for BB. BMD was measured using dual energy X‐ray absorptiometry (DXA). Results: BMD in lumbar spine, proximal femur, and total body increased with age, and the respective observed averages were: in CA1 (10 years old), 0.631, 0.692, 0.798 g/cm2; in CA2 (11 to 12 years old), 0.698, 0.763, 0.840 g/cm2; in CA3 (13 to 14 years old), 0.865, 0.889, 0.972 g/cm2; in CA4 (15 to 16 years old), 0.902, 0.922, 1.013 g/cm2; and in CA5 (17 to 19 years old), 0.944, 0.929, 1.35 g/cm2. These results showed significant differences between 13 and 14 years of age (CA3) or when girls reached the B3 stage (0.709, 0.832, 0.867 g/cm2). The highest median concentrations of BB were between 10 and 12 years of age when adolescents were in the B2–B3 (p

Bisphosphonates play an important role in the treatment of metabolic bone diseases such as osteoporosis. In addition to their anti-resorptive activity by triggering osteoclast apoptosis, nitrogen-containing bisphosphonates (N-BP) may also influence osteogenic differentiation, which might rely on their capacity to inhibit the mevalonate pathway. In vascular endothelial cells inhibition of this pathway by cholesterol-lowering statins activates the MEK5/ERK5 mitogen-activated protein kinase cascade, which plays an important role in cellular differentiation, apoptosis or inflammatory processes. Here we evaluated whether N-BP may also target the MEK5/ERK5 pathway and analysed the consequences of ERK5 activation on osteogenic differentiation. We show that N-BP dose-dependently activate ERK5 in primary human endothelial cells and osteoblasts. The mechanism likely involves farnesyl pyrophosphate synthase inhibition and subsequent functional inhibition of the small GTPase Cdc42 since siRNA-mediated knockdown of both genes could reproduce N-BP-induced ERK5 activation. ERK5 activation resulted in regulation of several bone-relevant genes and was required for calcification and osteogenic differentiation of bone marrow-derived mesenchymal stems cells as evident by the lack of alkaline phosphatase induction and alizarin-red S staining observed upon ERK5 knockdown or upon differentiation initiation in presence of a pharmacological ERK5 inhibitor. Our data provide evidence that N-BP activate the MEK5/ERK5 cascade and reveal an essential role of ERK5 in osteogenic differentiation and mineralization of skeletal precursors. [ABSTRACT FROM AUTHOR]

Abstract: Skeletal and connective tissue defects are the most striking symptoms in patients suffering from classical homocystinuria (HCU). Here, we determined body composition and bone mass in three mouse models of HCU and assessed whether a long‐term administration of enzyme replacement therapy (ERT) corrected the phenotype. The mouse models of HCU were analyzed using dual‐energy X‐ray absorptiometry and the data were complemented by plasma biochemical profiles. Both the mouse model lacking CBS (KO) and the one expressing human CBS mutant transgene on a mouse CBS null background (I278T) showed marked bone loss and decreased weight mostly due to a lower fat content compared with negative controls. In contrast, the HO mouse expressing the human CBS WT transgene on a mouse CBS null background showed no such phenotype despite similar plasma biochemical profile to the KO and I278T mice. More importantly, administration of ERT rescued bone mass and changes in body composition in the KO mice treated since birth and reversed bone loss and improved fat content in the I278T mice injected after the development of clinical symptoms. Our study suggests that ERT for HCU may represent an effective way of preventing the skeletal problems in patients without a restricted dietary regime. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) affects many organ systems including the skeleton. In children with IBD, bone mineral density (BMD) and bone turnover are frequently low. Disturbances in bone mineralization density distribution (BMDD) are linked to alterations in bone material strength; however, BMDD has not previously been reported in children with chronic inflammatory disorders. The aim of this study was to characterize BMDD based on quantitative backscatter electron imaging in cancellous (Cn.) and cortical (Ct.) compartments from trans-iliac biopsy samples from a cohort of 20 treatment-naïve children at the time of their IBD diagnosis (12 males, mean age 14.5 ± 2.3 years). The outcomes were compared to pediatric reference BMDD data and correlation with revisited biochemical and histomorphometric outcomes was analyzed. BMDD in treatment-naïve children with IBD was shifted toward higher calcium concentrations compared to reference: (i) In cancellous bone, the most frequent calcium concentration (Cn.CaPeak + 2.8%, p = 0.004) and the portion of highly mineralized bone (Cn.CaHigh + 52%, p = 0.009) were increased. (ii) In cortical bone, the mineralization heterogeneity (Ct.CaWidth + 17.0%, p = 0.001) and Ct.CaHigh (+ 30.4%, p = 0.006) were increased. (iii) Furthermore, significant correlations with serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bsALP), and urinary crosslinked N-telopeptide of type I collagen (uNTX) were observed: the higher CaMean (the average calcium concentration), CaPeak and CaHigh, the lower were ALP, bsALP, and uNTX (p-value from < 0.001 to 0.05). Children with treatment-naïve IBD have decreased bone turnover leading to a higher bone matrix mineralization density, findings which may contribute to compromised bone strength. [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic bone disease with an increasing prevalence in the elderly population. There is conflicting opinion about whether osteoporosis affects the alveolar bone of the jaws and whether it poses a risk to the osseointegration of dental implants. The aim of the present study was to evaluate the effects of systemic glucocorticoid administration on the jaw bone density of minipigs. Thirty-seven adult female minipigs were randomly divided into two groups. Quantitative computed tomography (QCT) was used to assess bone mineral density BMD of the lumbar spine as well as the mandible and maxilla, and blood was drawn. One group of minipigs initially received 1.0 mg prednisolone per kg body weight daily for 2 months. The dose was tapered to 0.5 mg per kg body weight per day thereafter. The animals in the other group served as controls and received placebo. QCT and blood analysis were repeated after 6 and 9 months. BMD was compared between the two groups by measuring Hounsfield units, and serum levels of several bone metabolic markers were also assessed. A decrease in BMD was observed in the jaws from baseline to 9 months. This was more pronounced in the prednisolone group. Statistically significant differences were reached for the mandible (p < 0.001) and the maxilla (p < 0.001). The administration of glucocorticoids reduced the BMD in the jaws of minipigs. The described model shows promise in the evaluation of osseointegration of dental implants in bone that is compromised by osteoporosis.

Los mayores picos de mineralización se producen en los primeros 2 años de vida y la pubertad, en los que la masa ósea aumenta 40% y 60%; a los 20 años se estabiliza y, luego, se inicia una pérdida progresiva. El volumen de masa ósea es variable según la edad, el sexo y la raza, es afectado por factores ambientales, genéticos, hormonales y nutricionales. El objetivo del estudio fue conocer el impacto de los hábitos relacionados con el proceso de mineralización durante la etapa de la juventud. Los participantes completaron una ficha clínica. La densidad mineral ósea fue valorada por medio de densitometría, se midieron los niveles de calcio en orina para identificar posibles pérdidas, se calculó el índice de masa corporal (IMC) a partir del peso y la talla. El 5% de la población participante presentó un Z-score inferior a -2,0 y los factores relacionados fueron consumo de cafeína, alcohol y poca actividad física. Abstract The highest peaks of mineralization is in the first two years of life and puberty, bone mass increases 40% to 60%, at twenty stabilizes and begins a gradual loss. The volume of bone mass varies according to age, sex and race, which affect environmental, genetic, hormonal and nutritional factors. The aim of the study was to determine the impact of the habits related mineralization process during the stage of youth. Participants completed clinical record. BMD was assessed by densitometry; Calcium levels were measured in urine for loss, BMI was calculated from weight and height. 5% of the participating population present a Z-score less than -2,0 and related factors were caffeine, alcohol and little physical activity.

A polyphenolic extract from melon (Cucumis melo L.), as a potential source of natural antioxidants, has been reported to have a positive effect on osteoblast activity. In this study, the protective effects of heat-treated melon extract (ECO-A) on bone strength, mineralization, and metabolism were examined in osteoporotic rat models. Osteoporosis was induced by ovariectomy (OVX) in female rats and then maintained for 8 weeks, along with the ingestion of phosphate-buffered saline (PBS, OVXP) or ECO-A (OVXE) for an additional 4 weeks. At a pre-determined timepoint, bone strengths, as well as bone mineral contents (BMC) and the density (BMD) of femurs and/or lumbar spines extracted from each animal, were measured by a mechanical test and dual-energy X-ray absorptiometry, respectively. Moreover, several biochemical markers for bone turnover were analyzed by respective colorimetric assay kits in addition to clinical analyses. The maximum load and stiffness of femurs from the OVXE group were found to be significantly higher than the other groups. Furthermore, the OVXE group showed significantly higher BMC, BMD, and bone volume than the OVX and OVXP groups, which were comparable to the non-OVX (sham) group. The levels of bone formation and resorption markers in the OVXE group were similar to the sham group, but significantly different from other groups. In conclusion, these results suggest that ECO-A can play potentially positive roles in the protection of bone loss in rats with OVX-induced osteoporosis.

Osteoporosis is a systemic bone disease with an increasing prevalence in the elderly population. There is conflicting opinion about whether osteoporosis affects the alveolar bone of the jaws and whether it poses a risk to the osseointegration of dental implants. The aim of the present study was to evaluate the effects of systemic glucocorticoid administration on the jaw bone density of minipigs. Thirty-seven adult female minipigs were randomly divided into two groups. Quantitative computed tomography (QCT) was used to assess bone mineral density BMD of the lumbar spine as well as the mandible and maxilla, and blood was drawn. One group of minipigs initially received 1.0mg prednisolone per kg body weight daily for 2 months. The dose was tapered to 0.5mg per kg body weight per day thereafter. The animals in the other group served as controls and received placebo. QCT and blood analysis were repeated after 6 and 9 months. BMD was compared between the two groups by measuring Hounsfield units, and serum levels of several bone metabolic markers were also assessed. A decrease in BMD was observed in the jaws from baseline to 9 months. This was more pronounced in the prednisolone group. Statistically significant differences were reached for the mandible (p < 0.001) and the maxilla (p < 0.001). The administration of glucocorticoids reduced the BMD in the jaws of minipigs. The described model shows promise in the evaluation of osseointegration of dental implants in bone that is compromised by osteoporosis. [ABSTRACT FROM AUTHOR]

Lead exposure has been associated with several defective skeletal growth processes and bone mineral alterations. The aim of the present study is to make a more detailed description of the toxic effects of lead intoxication on bone intrinsic material properties as mineral composition, morphology and microstructural characteristics. For this purpose, Wistar rats were exposed (n = 12) to 1000 ppm lead acetate in drinking water for 90 days while control group (n = 8) were treated with sodium acetate. Femurs were examined using inductively coupled plasma optical emission spectrometry (ICP-OES), Attenuated Total Reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), and micro-Computed Tomography (μCT). Results showed that femur from the lead-exposed rats had higher carbonate content in bone mineral and (Ca 2+ + Mg 2+ + Na + )/P ratio values, although no variations were observed in crystal maturity and crystallite size. From morphological analyses, lead exposure rats showed a decreased in trabecular bone surface and distribution while trabecular thickness and cortical area increased. These overall effects indicate a similar mechanism of bone maturation normally associated to age-related processes. These responses are correlated with the adverse actions induced by lead on the processes regulating bone turnover mechanism. This information may explain the osteoporosis diseases associated to lead intoxication as well as the risk of fracture observed in populations exposed to this toxicant. [ABSTRACT FROM AUTHOR]

Peripheral quantitative computed tomography provides an automatical scan analysis of trabecular and cortical bone compartments, calculating not only their bone mineral density (BMD), but also bone geometrical parameters, such as marrow and cortical Cross-Sectional Area (CSA), Cortical Thickness (CoTh), both periosteal and endosteal circumference, as well as biomechanical parameters like Cross-Sectional Moment of Inertia (CSMI), a measure of bending, polar moment of inertia, indicating bone strength in torsion, and Strength Strain Index (SSI). Also CSA of muscle and fat can be extracted. Muscles, which are thought to stimulate bones to adapt their geometry and mineral content, are determinant to preserve or increase bone strength; thus, pQCT provides an evaluation of the functional 'muscle-bone unit', defined as BMC/muscle CSA ratio. This functional approach to bone densitometry can establish if bone strength is normally adapted to the muscle force, and if muscle force is adequate for body size, providing more detailed insights to targeted strategies for the prevention and treatment of bone fragility. The present paper offers an extensive review of technical features of pQCT and its possible clinical application in the diagnostic of bone status as well as in the monitoring of the skeleton's health follow-up. [ABSTRACT FROM AUTHOR]

The macro- and micro-features of bone can be assessed by using imaging methods. However, nano- and molecular features require more detailed characterization, such as use of e.g. , vibrational spectroscopy and X-ray scattering. Nano- and molecular features also affect the mechanical competence of bone tissue. The aim of the present study was to reveal the effects of mineralization and its alterations on the mineral crystal scale, by investigating the spatial variation of molecular composition and mineral crystal structure across the cross-section of femur diaphyses in young rats, and healthy and osteoporotic mature rats ( N = 5). Fourier transform infrared spectroscopy and scanning small- and wide-angle X-ray scattering (SAXS/WAXS) techniques with high spatial resolution were used at identical locations over the whole cross-section. This allowed quantification of point-by-point information about the spatial distribution of mineral crystal volume. All measured parameters (crystal dimensions, degree of orientation and predominant orientation) varied across the cortex. Specifically, the crystal dimensions were lower in the central cortex than in the endosteal and periosteal regions. Mineral crystal orientation followed the cortical circumference in the periosteal and endosteal regions, but was less well-oriented in the central regions. Central cortex is formed rapidly during development through endochondral ossification. Since rats possess no osteonal remodeling, this bone remains (until old age). Significant linear correlations were observed between the dimensional and organizational parameters, e.g. , between crystal length and degree of orientation ( R 2 = 0.83, p < 0.001). Application of SAXS/WAXS provides valuable information on bone nanostructure and its constituents, effects of diseases and, prospectively, mechanical competence. [ABSTRACT FROM AUTHOR]

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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-1's effects on bone formation by upregulating anabolic processes without altering NELL-1's 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. [ABSTRACT FROM AUTHOR]

The utility of HR-CT to study longitudinal changes in bone microarchitecture is limited by subject radiation exposure. Although MR is not subject to this limitation, it is limited both by patient movement that occurs during prolonged scanning at distal sites, and by the signal-to-noise ratio that is achievable for high-resolution images in a reasonable scan time at proximal sites. Recently, a novel MR-based technique, fine structure analysis (FSA) (Chase et al. Localised one-dimensional magnetic resonance spatial frequency spectroscopy. PCT/US2012/068284 , James and Chase Magnetic field gradient structure characteristic assessment using one-dimensional (1D) spatial frequency distribution analysis. 7932720 B2, ) has been developed which provides both high-resolution and fast scan times, but which generates at a designated set of spatial positions (voxels) a one-dimensional signal of spatial frequencies. Appendix 1 provides a brief introduction to FSA. This article describes an initial exploration of FSA for the rapid, non-invasive characterization of trabecular microarchitecture in a preclinical setting. For L4 vertebrae of sham and ovariectomized (OVX) rats, we compared FSA-generated metrics with those from CT datasets and from CT-derived histomorphometry parameters, trabecular number (Tb.N), bone volume density (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). OVX caused a reduction of the higher frequency structures that correspond to a denser trabecular lattice, while increasing the preponderance of lower frequency structures, which correspond to a more open lattice. As one example measure, the centroid of the FSA spectrum (which we refer to as fSAcB) showed strong correlation in the same region with CT-derived histomorphometry values: Tb.Sp: r −0.63, p < 0.001; Tb.N: r 0.71, p < 0.001; BV/TV: r 0.64, p < 0.001, Tb.Th: r 0.44, p < 0.05. Furthermore, we found a 17.5 % reduction in fSAcB in OVX rats ( p < 0.0001). In a longitudinal study, FSA showed that the age-related increase in higher frequency structures was abolished in OVX rats, being replaced with a 78-194 % increase in lower frequency structures (2.4-2.8 objects/mm range), indicating a more sparse trabecular lattice ( p < 0.05). The MR-based fine structure analysis enables high-resolution, radiation-free, rapid quantification of bone structures in one dimension (the specific point and direction being chosen by the clinician) of the spine. [ABSTRACT FROM AUTHOR]

Copyright of Jornal de Pediatria is the property of Sociedade Brasileira de Pediatria 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.)

The strength of trabecular bone depends on its microarchitecture and its tissue level properties. However, the interrelation between these two determinants of bone quality and their relation to age remain to be clarified. Iliac crest bone cores ( n = 152) from individuals aged 30–90 years were analyzed by quantitative backscattered electron imaging. Univariate and multivariate analyses were conducted to determine whether epidemiological parameters (age, sex or BMI), structural histomorphometrical variables (BV/TV, Tb.Th, Tb.N and Tb.Sp) and osteoid-related indices (OV/BV, OS/BS or O.Th) predict the degree of bone mineralization. While sex and BMI were not associated with bone mineralization, age was positively correlated with the most frequently occurring calcium concentrations (Ca peak), the percentage of highly mineralized bone areas (Ca high) and, in the case of adjusted covariates, also the mean calcium content (Ca mean). Bone volume fraction and trabecular thickness were both negatively correlated with Ca mean. However, trabecular thickness was additionally associated with Ca peak, Ca high as well as the amount of low mineralized bone (Ca low) and was the only structural parameter predicting bone mineralization independent of age. Furthermore, our analyses demonstrated that osteoid variables – within a normal range (< 2% OV/BV) – were significantly associated with all mineralization parameters and represent the only predictor for the mineralization heterogeneity (Ca width). Taken together, we showed that elevated trabecular bone mineralization correlates with aging and bone loss. However, these associations are attributable to trabecular thinning that comes along with high bone mineralization due to the loss of low mineralized bone surfaces. Therefore, we demonstrated that the degree of areally resolved bone mineral is primarily associated with the amount of physiological osteoid present and the thickness of mineralized bone in trabeculae. [ABSTRACT FROM AUTHOR]

ABSTRACT Bone mineral deposition during the modeling of new bone and remodeling of old bone can be perturbed by several pathological conditions, including osteoporosis and skeletal metastases. A site-specific marker depicting the dynamics of bone mineral deposition would provide insight into skeletal disease location and severity, and prove useful in evaluating the efficacy of pharmacological interventions. Fluorescent labels may combine advantages of both radioisotope imaging and detailed microscopic analyses. The purpose of this study was to determine if the fluorescent bisphosphonate OsteoSense could detect localized changes in bone mineral deposition in established mouse models of accelerated bone loss (ovariectomy) (OVX) and anabolic bone gain resulting from parathyroid hormone (PTH) treatment. We hypothesized that the early rate of binding, as well as the total amount of bisphosphonate, which binds over long periods of time, could be useful in evaluating changes in bone metabolism. Evaluation of the kinetic uptake of bisphosphonates revealed a significant reduction in both the rate constant and plateau binding after OVX, whereas treatment with PTH resulted in a 36-fold increase in the bisphosphonate binding rate constant compared with untreated OVX controls. Localization of bisphosphonate binding revealed initial binding at sites of ossification adjacent to the growth plate and, to a lesser extent, along more distal trabecular and cortical elements. Micro-computed tomography (CT) was used to confirm that initial bisphosphonate binding is localized to sites of low tissue mineral density, associated with new bone mineral deposition. Our results suggest monitoring binding kinetics based on fluorescently labeled bisphosphonates represents a highly sensitive, site-specific method for monitoring changes in bone mineral deposition with the potential for translation into human applications in osteoporosis and bone metastatic processes and their treatment. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

A major skeletal problem of conventional-ly caged hens is increased susceptibility to osteoporosis mainly due to lack of exercise. Osteoporosis is charac-terized by a progressive decrease in mineralized struc-tural bone. Whereas considerable attention has been given to enriching laying cages, little research has been conducted on providing caged pullets with furnish-ments, in particular perches. The objective of the cur-rent study was to determine if metal perches during all or part of the life cycle of White Leghorns affected hen musculoskeletal health, especially at end of lay. Treat-ments during the pullet phase (hatch to 16.9 wk) en-tailed cages with and without perches. Four treatments were used during the laying phase (17 to 71 wk of age). Treatment 1 chickens never had access to perches at any point during their life cycle, typical of egg industry practices in the United States for conventional cages. Treatment 2 chickens had access to perches only during the egg-laying phase, which was from 17 to 71 wk of age. Treatment 3 chickens had access to perches only during the pullet phase (0 to 16.9 wk of age). Treatment 4 chickens had perch access throughout their entire life cycle (0 to 71 wk of age). Musculoskeletal health was assessed by measuring muscle weights, bone mineraliza-tion, bone fracture incidence, and keel bone deviations. Muscle deposition of 71-wk-old hens increased when given access to perches as pullets. Bone mineralization of 71-wk-old hens also increased if given perch access as adults. However, the disadvantage of the adult perch was the higher incidence of keel deviations and keel fractures at end of lay. The increase in bone mineraliza-tion of the keel bone as a result of perch access during the pullet and laying phases was not great enough to prevent a higher incidence of keel bone fractures at end of lay. Perch redesign and placement of perches within the cage to minimize keel fractures and deviations are possible solutions. [ABSTRACT FROM AUTHOR]

Aim: A layer-by-layer matrix (LBL) comprising kaempferol (LBL-KEM) was prepared for improved osteogenic action. Materials & methods: The LBL-KEM consisted of alternate layers of sodium alginate and protamine sulfate, which were sequentially deposited on the preformed kaempferol (KEM)-loaded CaCO3 core (CaCO3-KEM) by LBL self-assembly. The LBL matrix developed was evaluated for layer growth by ζ-potential and size alterations after self-assembly of each layer. Its physicochemical properties and intestinal absorption pattern were characterized and its pharmacokinetic behavior, mineralization of bone marrow cells, bone mineral density, bone strength, microcrack formation and estrogenicity were evaluated after oral administration. Results: The entrapment efficiency of KEM was 94 ± 2% and the cumulative %KEM released from LBL-KEM was 19.2 and 63.5% at pH 1.4 and 7.4, respectively, after 24 h. Stepwise polyelectrolyte assembly onto initially positively charged particles (+21.2 mV) resulted in alterations between -28.5 and +10.9 mV. A final ζ-potential of -8.9 mV was obtained after terminal surface modification with sodium deoxycholate. Fluorescein isothiocyanate-labeled LBL matrix was diffused into the basolateral lacteal region upon oral administration to rats. The area under the KEM serum concentration curve following oral administration of LBL-KEM to rats was 2479 ± 682 ng·h/ml, nearly twofold higher than free KEM. The concentration-time profile in bone marrow indicated improved penetration and retention of KEM on administration of LBL-KEM. Treatment with LBL-KEM restored bone mineralization, bone mineral density, microcrack formation and empty osteocyte lacunae density in ovariectomized (OVx) rats, which was significantly (p < 0.05) improved in femoral diaphysea, tibial head and vertebrae compared with free KEM treatment. Administration of LBL-KEM to growing female rats for 4 weeks resulted in no estrogenicity when compared with OVx rats. Conclusion: The data suggests that LBL matrix enhanced drug delivery, improved pharmacokinetics and maintained better bone quality under OVx conditions. [ABSTRACT FROM AUTHOR]

Abstract: There is a compromised bone mass in phenylketonuria patients compared with normal population, but the mechanisms responsible are still a matter of investigation. In addition, tetrahydrobiopterin therapy is a new option for a significant proportion of these patients and the prevalence of mineral bone disease (MBD) in these patients is unknown. We conducted a cross-sectional observational study including 43 phenylketonuric patients. Bone densitometry, nutritional assessment, physical activity questionnaire, biochemical parameters, and molecular study were performed in all patients. Patients were stratified by phenotype, age and type of treatment. The MBD prevalence in phenylketonuria was 14%. Osteopenic and osteoporotic (n=6 patients) had an average daily natural protein intake significantly lower than the remaining (n=37) patients with PKU (14.33±8.95g vs 21.25±20.85g). Besides, a lower body mass index was found. There were no statistical differences in physical activity level, calcium, phosphorus and fat intake, and in phenylalanine, vitamin D, paratohormone, docosahexaenoic and eicosapentaenoic acid blood levels. Mutational spectrum was found in up to 30 different PAH genotypes and no relationship was established among genotype and development of MBD. None of the twelve phenylketonuric patients treated with tetrahydrobiopterin (27.9%), for an average of 7.1years, developed MBD. Natural protein intake and blood levels of eicosapentaenoic acid were significantly higher while calcium intake was lower in these patients. This study shows that the decrease in natural protein intake can play an important role in MBD development in phenylketonuric patients. Therapy with tetrahydrobiopterin allows a more relaxed protein diet, which is associated with better bone mass. [Copyright &y& Elsevier]

Osteoporosis, a progressive decrease in mineralized structural bone, causes 20 to 35% of all mortalities in caged White Leghorn hens. Previous research has focused on manipulating the egg laying environment to improve skeletal health, with little research on the pullet. The objective of the current study was to determine the effect of perch access on pullet health, bone mineralization, muscle deposition, and stress in caged White Leghorns. From 0 to 17 wk of age, half of the birds were placed in cages with 2 round metal perches, while the other half did not have perches (controls). Bone mineralization and bone size traits were determined in the tibia, femur, sternum, humerus, ulna, radius, and phalange (III carpometacarpal) using dual energy x-ray absorptiometry. Muscle weights were obtained for the breast and left leg (drum and thigh). A sample of pullets from each cage was evaluated for foot health, BW, right adrenal weight, and packed cell volume. Most measurements were taken at 3, 6, and 12 wk of age. Access to perches did not affect breast muscle weight, percentage breast muscle, percentage leg muscle, bone mineral density, bone length, bone width, adrenal weight, packed cell volume, and hyperkeratosis of the foot-pad and toes. There were no differences in BW, bone mineral content, and leg muscle weight at 3 and 6 wk of age. However, at 12 wk of age, BW (P = 0.025), bone mineral content of the tibia, sternum, and humerus (P = 0.015), and the left leg muscle weight (P = 0.006) increased in pullets with access to perches as compared with controls. These results suggest that perch access has beneficial effects on pullet health by stimulating leg muscle deposition and increasing the mineral content of certain bones without causing a concomitant decrease in bone mineral density. [ABSTRACT FROM AUTHOR]

Abstract: Osteoporotic hip fractures represent a major public health problem associated with high human and economic costs. The anatomical variation of the tissue mineral density (TMD) and of the elastic constants in femoral neck cortical bone specimens is an important determinant of bone fragility. The purpose of this study was to show that a Synchrotron radiation microcomputed tomography system coupled with a multiscale biomechanical model allows the determination of the 3-D anatomical dependence of TMD and of the elastic constants (i.e. the mechanical properties of an anisotropic material) in human femoral neck. Bone specimens from the inferior femoral neck were obtained from 18 patients undergoing standard hemiarthroplasty. The specimens were imaged using 3-D synchrotron micro-computed tomography with a voxel size of 10.13μm, leading to the determination of the anatomical distributions of porosity and TMD. The elastic properties of bone tissue were computed using a multiscale model. The model uses the experimental data obtained at the scale of several micrometers to estimate the components of the elastic tensor of bone at the scale of the organ. Statistical analysis (ANOVA) revealed a significant effect of the radial position on porosity and TMD and a significant effect of axial position on TMD only. Porosity was found to increase in the radial direction moving from the periosteum inwards (p<10−5). At any given distance from the periosteum, porosity does not vary noticeably along the bone axis. TMD was found to be significantly higher (p<10−5) in the periosteal region than in other bone locations and decreases from the periosteal to the endosteal region with an average slope of 10.05g.cm−3.m−1, the decrease being faster in the porous part of the samples (average slope equal of 30.04g.cm−3.m−1) than in dense cortical bone. TMD was found to decrease from the distal to the proximal part of the femur neck (average slope of 6.5g.cm−3.m−1). Considering TMD variations in the radial direction induces weak changes of bone properties compared to constant TMD. TMD variations in the axial direction are responsible for a significant variation of elastic constants. These results demonstrate that the anatomical variations of TMD affect the bone elastic properties, which could be explained by the complex stress field in bone affecting bone remodeling. TMD spatial variations should be taken into account to properly describe the spatial heterogeneity of elastic coefficients of bone tissue at the organ scale. [Copyright &y& Elsevier]

The effect of osthol on osteoblasts was investigated in primary osteoblastic cells isolated from newborn Wistar rats. Osthol was supplemented into cultured medium at 10-7, 10-6, 10-5 and 10-4 mol/l, respectively. No stimulating effect was found on cell proliferation, but 10-5 mol/l osthol caused a significant increase in alkaline phosphatase (ALP) activity. Osteogenic differentiation markers were examined over a period of time at this concentration, and compared with control cells that were not supplemented with osthol. The results showed that the ALP activity, osteocalcin secretion and calcium deposition level in cells treated with osthol were 1.52, 2.74 and 2.0 times higher, respectively, than in the control cells. Results of ALP histochemical staining and mineralized bone nodule assays both showed that the number and area achieved in osthol-treated cells were 1.53-fold higher than in control cells. The gene expression of the growth and transcription factors basic fibroblast growth factor, insulin-like growth factor I, bone morphogenetic protein 2 (BMP-2), runt-related gene 2 (Runx-2) and osterix, which are associated with bone development, were also investigated. The increase in mRNA expression was 1.94, 1.74, 1.68, 1.83 and 2.31 times, respectively, higher compared to the control. Furthermore, osthol increased the protein expression of p38 mitogen-activated protein kinase (MAPK) and type I collagen. p38MAPK protein and collagen in osthol-treated cells were 1.42 and 1.58 times higher in osthol-treated cells compared to the control. The results of these studies support the conclusion that osthol significantly enhances the osteogenic differentiation of cultured osteoblasts. The results also indicated that osthol could stimulate the osteoblastic differentiation of rat calvarial osteoblast cultures by the BMP-2/p38MAPK/Runx-2/osterix pathway and that osthol may be used as an important compound in the development of new antiosteoporosis drugs. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Egg-laying strains of chickens are highly susceptible to osteoporosis, a noninfectious disease characterized by a decrease in structural bone as hens age. To minimize the onset of osteoporosis, it was hypothesized that a delay in sexual maturity may allow a pullet to develop a stronger skeletal frame before egg laying, leading to improved skeletal mineralization at end of lay. One management tool that can easily be implemented by pullet growers to delay sexual maturity is length of photoperiod. The objective of the current study was to determine whether lighting programs used during the pullet phase of egg-laying strains of chickens can be manipulated to allow for improved skeletal mineralization in laying hens at end of lay. Two experiments were conducted in which 1,000 pullets/experiment were exposed to 1 of 3 varying step-down lighting programs (2 to 17 wk of age), referred to as rapid, moderate, and slow. For both experiments, 2 strains of chickens were used. Experiment 1 compared the Hy-Line W-36 with the Hy-Line W-98, and experiment 2 compared the Hy-Line Brown with the Hy-Line W-98. At 66 wk of age, all hens remaining in the study were weighed individually and the drum stick and wing were retrieved for determination of bone mineralization and bone size traits. Bone data were analyzed using an analysis of covariance with BW as the covariant, and BW was analyzed as an ANOVA. Skeletal frame development was affected by lighting regimen. Pullets exposed to the slow lighting photoperiod had longer bones and more bone area (experiment 2) than those exposed to the rapid photoperiod, most likely because of a delay in bone growth plate closure, which occurs at sexual maturity. However, this delay in sexual maturity, as indicated by longer bones, did not improve bone mineralization at 66 wk of age. It was concluded that pullet lighting regimen had little effect on bone mineralization at end of lay. [ABSTRACT FROM AUTHOR]