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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]

This study aimed to demonstrate the immunolocalization and gene expression of tissue nonspecific alkaline phosphatase (TNALP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) in osteoblasts, preosteoblasts, and osteocytes of murine bone to provide clues for a better understanding of the supply of phosphate ions (Pi) during bone mineralization. Six-week-old male C57BL/6J mice (n = 6) were fixed with a paraformaldehyde solution, and the right femora were extracted for immunodetection of TNALP and ENPP1, while the left tibiae were used for reverse transcription polymerase chain reaction to evaluate Tnalp and Enpp1 gene expression. TNALP was intensely localized on the basolateral cell membranes of mature osteoblasts and preosteoblastic cells. There was little immunoreactivity of TNALP on the secretory surface of the osteoblasts and no TNALP reactivity in the osteocytes. In contrast, ENPP1 was observed throughout the cytoplasm of mature osteoblasts and osteocytes embedded in bone but was not observed in preosteoblasts. Together, despite the fact that the osteoid is a site of matrix vesicle-mediated mineralization, ENPP1, which inhibits mineralization by providing pyrophosphates, was localized in close proximity of the osteoid, whereas TNALP, which facilitates mineralization by providing Pi, was relatively distant from the osteoid. It seems likely that the differential localization of TNALP and ENPP1 around the osteoid observed at the microscopic level may provide preferential micro-circumstance for a balanced concentration of Pi and pyrophosphate for bone mineralization. [ABSTRACT FROM AUTHOR]

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

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

Captive rearing programs have been initiated to save the European common spadefoot ( Pelobates fuscus), a toad species in the family of Pelobatidae, from extinction in The Netherlands. Evaluating whether this species needs ultraviolet B (UVB) radiation and/or dietary supplementation for healthy bone development is crucial for its captive management and related conservation efforts. The bone mineralization in the femurs and the thickest part of the parietal bone of the skulls of European common spadefoots ( n = 51) was measured in Hounsfield units (HUs) by computed tomography. One group, containing adults ( n = 8) and juveniles ( n = 13), was reared at ARTIS Amsterdam Royal Zoo without UVB exposure. During their terrestrial lifetime, these specimens received a vitamin-mineral supplement. Another group, containing adults ( n = 8) and juveniles ( n = 10), was reared and kept in an outdoor breeding facility in Münster, Germany, with permanent access to natural UVB light, without vitamin-mineral supplementation. The HUs in the ARTIS and Münster specimens were compared with those in wild specimens ( n = 12). No significant difference was found between the HUs in the femurs of both ARTIS and Münster adults and wild adults ( P = 0.537; P = 0.181). The HUs in the skulls of both captive-adult groups were significantly higher than in the skulls of wild specimens ( P = 0.020; P = 0.005). The HUs in the femurs of the adult ARTIS animals were significantly higher than the HUs in the femurs of the adult Münster animals ( P = 0.007). The absence of UVB radiation did not seem to have a negative effect on the bone development in the terrestrial stage. This suggests that this nocturnal, subterrestrial amphibian was able to extract sufficient vitamin D3 from its diet and did not rely heavily on photobiosynthesis through UVB exposure. [ABSTRACT FROM AUTHOR]

In this review the authors outline traditional antiresorptive pharmaceuticals, such as bisphosphonates, monoclonal antibodies against RANKL, SERMs, as well as a drug with an anabolic effect on the skeleton, parathormone. However, there is also a focus on non-traditional strategies used in therapy for osteolytic diseases. The newest antiosteoporotic pharmaceuticals increase osteoblast differentiation via BMP signaling (harmine), or stimulate osteogenic differentiation of mesenchymal stem cells through Wnt/β-catenin (icarrin, isoflavonoid caviunin, or sulfasalazine). A certain promise in the treatment of osteoporosis is shown by molecules targeting non-coding microRNAs (which are critical for osteoclastogenesis) or those stimulating osteoblast activity via epigenetic mechanisms. Vitamin D metabolites have specific antiosteoporotic potencies, modulating the skeleton not only via mineralization, but markedly also through the direct effects on the bone microstructure. [ABSTRACT FROM AUTHOR]

Objective In the hypothalamic arcuate nucleus (ARC), orexigenic agouti-related peptide (AgRP) neurons regulate feeding behavior and energy homeostasis, functions connected to bone metabolism. The 3-phosphoinositide-dependent protein kinase-1 (PDK1) serves as a major signaling molecule particularly for leptin and insulin in AgRP neurons. We asked whether PDK1 in AGRP neurons also contributes to bone metabolism. Methods We generated AgRP neuron-specific PDK1 knockout ( Agrp Pdk1 −/− ) mice and those with additional AgRP neuron-specific expression of transactivation-defective FoxO1 ( Agrp Pdk1 −/− Δ256Foxo1 ). Bone metabolism in KO and WT mice was analyzed by quantitative computed tomography (QCT), bone histomorphometry, measurement of plasma biomarkers, and qPCR analysis of peptides. Results In Agrp Pdk1 −/− female mice aged 6 weeks, compared with Agrp Cre mice, both stature and femur length were shorter while body weight was unchanged. Cortical bone mineral density (BMD) and cancellous BMD in the femur decreased, and bone formation was delayed. Furthermore, plasma GH and IGF-1 levels were reduced in parallel with decreased mRNA expressions for GH in pituitary and GHRH in ARC. Osteoblast activity was suppressed and osteoclast activity was enhanced. These changes in stature, BMD and GH level were rescued in Agrp Pdk1 −/− Δ256Foxo1 mice, suggesting that the bone abnormalities and impaired GH release were mediated by enhanced Foxo1 due to deletion of PDK1. Conclusions This study reveals a novel role of PDK1-Foxo1 pathway of AgRP neurons in controlling bone metabolism primarily via GHRH-GH-IGF-1 axis. [ABSTRACT FROM AUTHOR]

Bioinspired in vitro collagen mineralization experiments have been performed in the presence of citrate and the combined role of the two bone organic matrix components in controlling mineral formation was investigated for the first time. Mineralized and non-mineralized collagen fibrils have been in depth characterized by combining small- and wide-angle X-ray scattering (SAXS/WAXS) techniques with Atomic Force Microscopy (AFM) imaging. A synergic effect of collagen and citrate in driving the formation of long-term stable amorphous calcium phosphate (ACP) nanoparticles with platy morphology was found. AFM images on mineralized collagen fibrils revealed that some of the ACP nanoparticles were deposited on the intramolecular nanoscopic holes of collagen fibrils. Statement of Significance Citrate is an important component of the bone organic matrix but its specific role in bone mineralization is presently unclear. In this work, bioinspired in vitro collagen mineralization experiments in the presence of citrate have been carried out and the combined role of collagen and citrate in controlling mineral formation has been addressed for the first time. Through X-ray scattering and Atomic Force Microscopy characterizations on mineralized and non-mineralized collagen fibrils, we have found that citrate in synergy with collagen stabilizes an amorphous calcium phosphate (ACP) phase with platy morphology over one week and controls its deposition on collagen fibrils. [ABSTRACT FROM AUTHOR]

Bone mineralization of preterm infants is significantly less than full-term infants at birth, placing preterm infants at risk for osteopenia of prematurity and other metabolic bone diseases. Advances in nutritional supplementation and standard nursing care alone have been unsuccessful in improving bone mineralization postnatally. Research supports a daily physical activity protocol of passive range of motion and gentle joint compression when combined with adequate nutritional supplementation reduces osteopenia of prematurity. This article provides a systematic review of the current evidence surrounding early physical activity and neonatal massage for the treatment of osteopenia and indicates the need for universal handling protocols in caring for this unique population. [ABSTRACT FROM AUTHOR]

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. • Parental BPA exposure declined quality of zebrafish embryo. • Parental BPA exposure affected bone development of zebrafish offspring. • MAPK/Wnt/FoxO pathways were involved in the intergenerational toxicity of BPA. • Long-term parental BPA exposure caused more serious harm on zebrafish offspring. • Toxicity of BPA at high dose on zebrafish offspring was higher than low dose. [ABSTRACT FROM AUTHOR]

• Pharmacological blockade of FAK results in reduced ALP expression and mineralization by differentiated osteoblasts. • Although FAK inhibition resulted in increased levels of BMP2, Wnt3a and Mdm2, and decreased p53, alteration of these pathways was unable to restore mineralization in the presence of FAK tyrosine kinase inhibitors. • FAK tyrosine kinase inhibitors resulted in decreased levels of phospho-S473 Akt which led to increased levels of active GSK3β which in turn inhibited Runx2 activity that could contribute to the observed reduced ALP levels. • FAK tyrosine kinase inhibitors blocked Akt-mediated stabilization of osterix leading to decreased overall levels of osterix and impaired mineralization in MC3T3-E1 cells differentiated into osteoblasts. Focal Adhesion Kinase (FAK) is an important regulator of tumor cell proliferation, survival and metastasis. As such it has become a therapeutic target of interest in cancer. Previous studies suggested that use of FAK tyrosine kinase inhibitors (TKIs) blocks osteolysis in in vivo models of bone metastasis. However, from these studies it was not clear whether FAK TKIs blocked bone degradation by osteoclasts or also promoted bone formation by osteoblasts. In this study we evaluated whether use of the FAK TKI PF-562,271 affected the differentiation of pre-osteoblasts, or activity of mature differentiated osteoblasts. MC3T3-E1 pre-osteoblastic cells were treated with various doses of PF-562,271 following 3 or 10 days of differentiation which led to the inhibition of alkaline phosphatase (ALP) expression and reduced viable cell numbers in a dose-dependent manner. MC3T3-E1 cells which had been differentiated for 21 days prior to treatment with PF-562,271 showed a dose dependent decrease in mineralization as assessed by Alizarin Red staining, with concomitant decreased expression of ALP which is known to facilitate the bone mineralization activity of osteoblasts, however mRNA levels of the transcription factors RUNX2 and osterix which are important for osteoblast maturation and mineralization appeared unaffected at this time point. We speculated that this may be due to altered function of RUNX2 protein due to inhibitory phosphorylation by GSK3β. We found treatment with PF-562,271 resulted in increased GSK3β activity as measured by reduced levels of phospho-Ser9-GSK3β which would result in phosphorylation and inhibition of RUNX2. Treatment of 21 day differentiated MC3T3-E1 cells with PF-562,271 in combination with GSK3β inhibitors partially restored mineralization however this was not statistically significant. As we observed that FAK TKI also resulted in suppression of Akt, which is known to alter osterix protein stability downstream of RUNX2, we examined protein levels by western blot and found a dose-dependent decrease in osterix in FAK TKI treated differentiated MC3T3-E1 cells which is likely responsible for the reduced mineralization observed. Taken together our results suggest that use of FAK TKIs as therapeutics in the bone metastatic setting may block new bone formation as an off-target effect and thereby exacerbate the defective bone regulation that is characteristic of the bone metastatic environment. [ABSTRACT FROM AUTHOR]

Abstract: A most common and trusted source of Ca is milk or other dairy products. However, some oriental people do not drink milk due to lactose indigestion and intolerance, which make them allergic to milk. There have been many studies on alternative calcium-rich diet or Ca supplements. Among them, teleost fish like anchovy and mola, which are commonly consumed in Asian countries, could be an important Ca dietary supplement, especially in population groups with low intakes of milk and dairy products. In this chapter, we summarize beneficial effects of teleost fish bone peptide (FBP) for Ca bioavailability and bone mineralization, based on our researches. [Copyright &y& Elsevier]

The article discusses a study which determined the role of two milk micronutrients namely, calcium (Ca) and inorganic phosphate (Pi) on bone structure and function. The study provided insight into the mechanisms underlying the micronutrients' deposition onto the organic matrix and how they can influence bone cell functions by several distinct cellular pathways. It also looked into fluctuations in Ca and Pi and how dietary Ca and Pi interact with bone acquisition and maintenance.

In order to identify biomarkers of oil pollution in fish we tested the effects of an experimental Light Cycle Oil (LCO) exposure on vertebral bone of sea bass, Dicentrarchus labrax L. A total of 60 adult fish were acclimated for fifteen days, then twenty were collected as controls (Day 0) while 40 were exposed to a soluble fraction of LCO (1136ngL−1 of ten Polycyclic Aromatic Hydrocarbons, PAHs) for seven days. Twenty of them were sampled at the end of the exposure period and the twenty last after a recovery period of fourteen days in clean seawater. Vertebral abnormalities were counted and bone mineralization, total bone area and bone density profiles were established for several post-cranial and caudal vertebrae. In sea bass, seven days of LCO exposure did not affect the frequency and severity of the vertebral abnormalities. No significant differences were observed in bone density and bone repartition (parameters of bone area profiles) between unexposed (Day 0), exposed (D7) and decontaminated (D21) fish. In contrast, bone mineralization of the vertebrae decreased in contaminated sea bass, but in a reversible way, which confirms a previous study in trout showing that this parameter is an early stress indicator. Our results suggest that vertebral bone mineralization could be used as a biomarker of PAH pollution in sea bass. It would be interesting to check this new biomarker in other teleost species exposed to various xenobiotics. [Copyright &y& Elsevier]

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Summary: A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in up to 85% of adult patients and osteoporosis in 10% to 34%. In children, study results are discordant probably because of comparisons to different control populations and corrections for bone size in growing children. Malnutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period for bone mineralization and requires a careful follow-up to achieve optimal bone peak mass. Strategies for optimizing bone health, such as monitoring bone mineral density (BMD) and providing preventive care are necessary from childhood through adolescence to minimize CF-related bone disease in adult CF patients. [Copyright &y& Elsevier]

Abstract: Long-lived species are particularly susceptible to bioaccumulation of lead in bone tissues. In this paper we gain insights into the sublethal effects of lead contamination on Egyptian vultures (Neophron percnopterus). Our approach was done on the comparison of two populations (Canary Islands and Iberian Peninsula) differing in exposures to the ingestion of lead ammunition. Blood lead levels were higher in the island population (Canary Islands range: 5.10–1780μg L−1 n =137; Iberian Peninsula range: 5.60–217.30μg L−1 n =32) showing clear seasonal trends, peaking during the hunting season. Moreover, males were more susceptible to lead accumulation than females. Bone lead concentration increased with age, reflecting a bioaccumulation effect. The bone composition was significatively altered by this contaminant: the mineralization degree decreased as lead concentration levels increased. These results demonstrate the existence of long-term effects of lead poisoning, which may be of importance in the declines of threatened populations of long-lived species exposed to this contaminant. [Copyright &y& Elsevier]

The article presents a study which examined the effect of higher concentrations of vitamin D3 in diets containing same concentrations of calcium (Ca) and non-phytate phosphorus (NPP) on performance, bone mineralization, mineral excretion and mineral retention in broiler starter chicks compared to those fed the recommended levels of Ca, NPP and D3. The results of the study indicated the possibility of increased performance and mineral utilization in commercial broiler chicks fed sub-optimal concentrations of Ca and NPP.

Background: Bone regeneration techniques increasingly rely on the use of exogenous molecules able to enhance tissue formation in pathologic and traumatic defects. An enamel matrix derivative (EMD) has been largely used to promote tooth ligament regeneration within periodontal pockets. Recent evidence suggests that EMD may contribute to inducing osteoblast growth and differentiation. We investigated the effects of EMD on growth and osteogenic marker modulation in human mandibular osteoblasts. Methods: We focused our attention on cell growth by 3- (4,5-dimethyl[thiazol-2-yl]-3,5-diphery)tetradium bromide (MTT) assay, cell differentiation, mineralized nodule formation, and, in particular, the expression of receptor activator of nuclear factor-kappa B ligand (RANKL), the main osteoclast differentiation factor, and its decoy receptor, osteoprotegerin (OPG), by enzyme-linked immunosorbent assay. Results: Cell growth was significantly increased by EMD. Similarly, a significantly higher quantity of OPG and a lower amount of RANKL were detectable in groups treated with 50 and 100 µg/ml at weeks 1,2, and 3, and alkaline phosphatase activity and osteocalcin production were enhanced in cultures treated with 50 and 100 µg/ml at weeks 2 and 3. Mineralized nodules appeared bigger and more numerous in cultures treated with 50 and 100 µg/ml EMD. Conclusions: EMD was able to enhance osteoblast cell growth and the expression of markers of osteoblastic phenotype and differentiation. EMD also seemed able to create a favorable osteogenic microenvironment by reducing RANKL release and enhancing osteoblastic OPG production. [ABSTRACT FROM AUTHOR]

Abstract: Since there is almost no information on whether the concomitant use of diagnostic radioisotopes and radiographic contrast media interferes with dual-energy X-ray absorptiometry (DXA), we investigated these potentially confounding effects. At routine scheduled radiographic follow-up, 40 patients previously treated for malignant lymphomas or solid tumors in Hamilton and Ottawa, Canada were evaluated, 10 in each of the following 4 categories of diagnostic procedure: (1) computed tomography (CT) with intravenous, iodine-based contrast (± oral contrast), (2) magnetic resonance imaging (MRI) with gadolinium-based contrast, (3) gallium scan (GS), and (4) technetium bone scan (TBS). Whole body bone mineral content (WB-BMC) and lumbar spine bone mineral density (LS-BMD), total fat mass (TFM), and lean body mass (LBM) were measured by DXA immediately before and after the other radiological studies (on the same day) and then 7 days later. No statistically significant differences were found among WB-BMC, LS-BMD, TFM, and LBM Z-scores immediately before and after MRI, GS, TBS, and 7 days later. The DXA measurements performed immediately before and after CT showed statistically significant differences in WB-BMC (100% vs 124.5%, p <0.001), TFM (100% vs 75.4%, p <0.001), and LBM (100% vs 110%, p <0.001), resulting from the CT contrast agents compromising the precision of the DXA. The DXA results after 7 days were not statistically different from those at baseline. Dual-energy X-ray absorptiometry can be performed in association with other radiological techniques, with the exception of CT conducted with contrast within 1 week. This study provides information that applies not only to patients with cancer but to the general population undergoing diagnostic procedures. [Copyright &y& Elsevier]

Summary: Introduction: This study aimed at assessing the effect of radiotherapy on regenerated bone mineralization and consolidation obtained by mandibular bone distraction. The planned application was a new immediate mandibular reconstruction technique in defects following surgery for oral cavity tumours requiring postoperative radiotherapy. Material and methods: Ten sheep underwent bilateral mandibular bone distraction (control group). A second group of 6 sheep (study group) had bilateral mandibular bone distraction followed by irradiation on the 21st postoperative day. The animals were sacrificed on the 60th postoperative day. Radiographic and histomorphometric studies were performed. Results: In the control group, 9 distraction sites out of 20 were consolidated. In the irradiated group, 9 out of 12 were consolidated. Histomorphometric analysis did not demonstrate any statistically significant difference between the osseous and cartilaginous samples, the trabecular thickness of the new bone, or the osteoid surface of basal bone in the control and test groups (, , , ). However, the osteoid surface of the regenerated bone in the test group was statistically smaller () than in the control group. Conclusion: In this experiment, radiotherapy did not hinder bone mineralization or consolidation following distraction of mandibular bone receiving irradiation on the 21st postoperative day. Bone distraction could be proposed for the repair of mandibular defects following surgery for oral tumours which require early postoperative radiotherapy. [Copyright &y& Elsevier]

Abstract: The medical management of children with congenital adrenal hyperplasia (CAH) can be challenging with regard to optimizing final height. Insufficient glucocorticoid suppression of adrenal hormone production will result in acceleration of bone maturation and premature epiphyseal fusion, while appropriate or excessive glucocorticoid therapy can be accompanied by suppression of the growth axis. The extent of the growth suppression appears to be affected by the type and dose of glucocorticoid. Some studies suggest that such growth suppression can be ameliorated through concomitant use of growth hormone (GH) therapy. Available data published over the last 10 years on height outcomes in CAH patients treated with glucocorticoids will be reviewed. [Copyright &y& Elsevier]

Investigates the effects of dietary phosphorus (P) intake on bone mineralization and calcium (Ca) absorption in adult female rats. Results indicating that the low-P diet increased Ca absorption, this being effective for bone mineralization in adult female rats; Significant increase of the apparent Ca absorption with decreasing dietary P level; Increase in the bone mineral density of the fifth lumbar vertebra with decreasing dietary P level.

Background: Non-collagenous proteins of mineralized tissues play important roles in bone induction during mineralization and in regulating the activity of many types of mesenchymal cells. This study was conducted to determine the effects of acetic acid extracts of bone and cementum on alkaline phosphatase (ALPase) activity and in vitro mineralization of cultured human periodontal fibroblasts (hPF). Methods: Alveolar bone and cementum obtained from clinically healthy subjects were extracted by a solution containing 0.5 M acetic acid and enzyme inhibitors. Osteoblastic phenotypes of hPF were assayed by ALPase activity, gene expression of bone marker proteins, and the ability to produce in vitro mineralization in culture media containing 50 µ/ml ascorbic acid, 10 mM sodium β-glycerophosphdte, and 107 M dexamethasone. The effects of cementum and bone extracts on the expression of osteoblastic phenotypes in hPF were also determined. Results: Many protein components, varying in molecular weight from 10 to 14 to 120 kDa, were detectable in 10% SDS-PAGE of both cementum and alveolar bone extracts. The hPF cells were found to exhibit a moderate ALPase activity when compared with rat osteosarcoma (ROS) 17/2.8 cells under the same experimental conditions. Gene expression for ALPase, osteocalcin bone sialoprotein, osteopontin, and BMP-7 at mRNA message was detected by RT-PCR in hPF and ROS 17/2.8 cells. The confluent hPF and ROS 17/2.8 cells showed evidence of calcium deposition in the extracellular milieu at 30 and 15 to 30 days' cultures, respectively, under a mineralization medium. The hPF appeared to form mineralized foci with morphological characteristics different from the mineralized nodules produced by ROS 17/2.8 cells. The addition of low concentrations (5 µ/ml) of either cementum or bone extract produced an increase in the size and number of mineralization spots, as well as greater ALPase activity in both hPF and ROS 17/2.8 cultures during the observation periods. Conclusions: These results suggest that hPF possess certain mineralizing phenotypes, and that acetic acid extracts of bone and cementum contain components capable of stimulating osteogenic differentiation of hPF. [ABSTRACT FROM AUTHOR]

PROTEINS ASSOCIATED WITH THE MINERAL PHASE of denim are considered to have the potential to alter cell function within the local environment, during development and regeneration of tooth/periodontal tissues. Cells that may be altered include osteoblasts, ameloblasts, periodontal ligament cells, odontoblasts, and cementoblasts. However, specific factors within dentin controlling cell activity have not been elucidated. To investigate further the role of dentin proteins in regulating cell behavior. MC3T3-E1 cells, a mouse osteoprogenitor cell line, were exposed to guanidine/EDTA extracts of dentin (G/E-D) prepared from bovine teeth. Cells, with or without G/E-D (2 to 50 µg/ ml), were evaluated for proliferative activity and for mRNA expression of bone-associated genes. Results indicated that G/E-D suppressed cell proliferation and caused striking morphological changes, including the conversion of cuboidal cells into fibroblastic, spindle-shaped cells. Markers of osteoblast differentiation, osteocalcin and bone sialoprotein mRNA were decreased, while osteopontin mRNA was enhanced in cells exposed to G/E-D. Since transforming growth factor beta (TGFβ1) has been reported to influence cells in a similar fashion. G/E-D were examined for the presence of and concentration of TGFβ using slot blot analysis and enzyme immunoassay (ELI-SA), respectively. These analyses demonstrated that G/E-D contained 6.6 ng/mg of TGFβ1. Next, cells were exposed to G/E-D in conjunction with anti-TGFβ1,2,3 antibody. When cells were exposed to antibody, G/E-D-mediated changes in morphology and gene expression were blocked. These results suggest that TGFβ1, and perhaps other factors in dentin can regulate cell behavior and, therefore, can influence development, remodeling, and regeneration of mineralized tissues. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between maternal body mass index (BMI) and serum 25-hydroxy vitamin D [25(OH)D] concentration and bone density in mother-infant pairs.Study Design: The study was a secondary analysis of 234 exclusively breastfeeding dyads who were recruited in the first postpartum month for a randomized controlled trial of maternal vs infant vitamin D supplementation. Mean 25(OH)D concentrations and bone mineral density (BMD) were compared by BMI group. The adjusted association between maternal BMI and 25(OH)D and bone density was examined at 1, 4, and 7 months postpartum.Results: Obese breastfeeding women had lower 25(OH)D concentrations and higher BMD than lean women at all 3 time points (P  <  .01). Higher maternal BMI was associated with lower maternal serum levels of 25(OH)D at 1, 4, and 7 months postpartum (adjusted β = -0.45 ng/ml per kg/m2, 95% CI -.076, -0.14, at 1 month) and higher BMD at the same time points (β = 0.006 BMD z score; 95% CI 0.003, 0.01 at 1 month). Seventy-six percent of infants were vitamin D deficient at 1 month of age. Infants born to overweight and obese mothers had lower 25(OH)D concentrations than infants of lean mothers (P < .01). For infants in the maternal supplementation group, higher maternal BMI was associated with lower 25(OH)D concentrations at 4 months (β = -0.68; 95% CI -1.17, -0.20) and lower bone density at 7 months (β = -0.001; 95% CI -0.002, -0.0001).Conclusions: In exclusively breastfeeding dyads, maternal obesity is associated with lower maternal and infant serum 25(OH)D concentrations, which may impact infant bone density.Trial Registration: ClinicalTrials.gov: NCT00412074. [ABSTRACT FROM AUTHOR]