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The Journal of Clinical Endocrinology... Apr 2024Denosumab is an effective treatment for many receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated disorders but there are potential safety considerations...
CONTEXT
Denosumab is an effective treatment for many receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated disorders but there are potential safety considerations and limited data to guide its use in children and adolescents.
OBJECTIVE
This document seeks to summarize the evidence and provide expert opinion on safe and appropriate use of denosumab in pediatric RANKL-mediated disorders.
PARTICIPANTS
Ten experts in pediatric bone and mineral medicine from 6 countries with experience in the use of denosumab participated in the creation of this document.
EVIDENCE
Data were sourced from the published literature, primarily consisting of case reports/series and review articles because of the lack of higher level evidence. Expert opinion of the authors was used substantially when no published data were available.
CONCLUSION
Denosumab is an effective treatment for RANKL-mediated disorders in children and adolescents but is often not curative and, in some cases, is best used in conjunction with surgical or other medical treatments. Careful multidisciplinary planning is required to define the goals of treatment and expert oversight needed to manage the risk of mineral abnormalities. Substantive, collaborative research efforts are needed to determine optimal treatment regimens and minimize risks.
Topics: Adolescent; Child; Humans; Bone and Bones; Bone Density Conservation Agents; Denosumab; Ligands; Minerals; RANK Ligand
PubMed: 38041865
DOI: 10.1210/clinem/dgad657 -
Advanced Science (Weinheim,... Sep 2023Advanced functional two-dimensional (2D) nanomaterials offer unique advantages in drug delivery systems for disease treatment. Kaolinite (Kaol), a nanoclay mineral, is a... (Review)
Review
Advanced functional two-dimensional (2D) nanomaterials offer unique advantages in drug delivery systems for disease treatment. Kaolinite (Kaol), a nanoclay mineral, is a natural 2D nanomaterial because of its layered silicate structure with nanoscale layer spacing. Recently, Kaol nanoclay is used as a carrier for controlled drug release and improved drug dissolution owing to its advantageous properties such as surface charge, strong biocompatibility, and naturally layered structure, making it an essential development direction for nanoclay-based drug carriers. This review outlines the main physicochemical characteristics of Kaol and the modification methods used for its application in biomedicine. The safety and biocompatibility of Kaol are addressed, and details of the application of Kaol as a drug delivery nanomaterial in antibacterial, anti-inflammatory, and anticancer treatment are discussed. Furthermore, the challenges and prospects of Kaol-based drug delivery nanomaterials in biomedicine are discussed. This review recommends directions for the further development of Kaol nanocarriers by improving their physicochemical properties and expanding the bioapplication range of Kaol.
Topics: Drug Carriers; Kaolin; Drug Delivery Systems; Nanostructures; Anti-Bacterial Agents
PubMed: 37344357
DOI: 10.1002/advs.202300672 -
International Journal of Oral Science Dec 2023Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated...
Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.
Topics: Mice; Animals; Durapatite; Dental Enamel; Ameloblasts; Amelogenesis; Stem Cells; Organoids
PubMed: 38062012
DOI: 10.1038/s41368-023-00257-w -
Journal of Bone and Mineral Research :... Nov 2023Researchers have reported increased fracture risk in patients with anorexia nervosa (AN), but more knowledge on the long-term risk and the effects of age, male sex, and...
Researchers have reported increased fracture risk in patients with anorexia nervosa (AN), but more knowledge on the long-term risk and the effects of age, male sex, and time-related changes is still needed. We examined the long-term (up to 40 years) fracture risk among patients with AN compared to a matched comparison cohort from the general population. We utilized data from the Danish Health Care Registers to identify 14,414 patients with AN (13,474 females and 940 males) diagnosed between 1977 and 2018, with a median age of 18.6 years and median follow-up time of 9.65 years. We calculated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox regression analysis for overall and site-specific fracture risks. The overall aHR of any fracture was 1.46 [95% CI: 1.36 to 1.48], with an aHR of 1.50 [95% CI: 1.43 to 1.57] for females and 0.95 [95% CI: 0.82 to 1.1] for males. For specific fractures we found an association with femur fractures both in females 4.06 [95% CI: 3.39 to 4.46] and in males 2.79 [95% CI: 1.45 to 2.37] and for fractures of the spine (females 2.38 [95% CI: 2.00 to 2.84], males 2.31 [95% CI: 1.20 to 4.42]). The aHR of any fracture decreased from 1.66 [95% CI: 1.52 to 1.81] in the period from 1977 to 1997 to 1.40 [95% CI: 1.33 to 1.40] from 1998 to 2018. In conclusion, we found that AN was associated with a 46% increased risk of any fracture up to 40 years after diagnosis. We found no overall increased risk in males, but in both sexes we found a particularly high site-specific fracture risk in the spine and femur. Fracture risk decreased in recent decades, indicating that more patients with AN have been diagnosed with presumably less severe disease and that the earlier detection and intervention of AN in recent years may translate into a lower facture risk. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Female; Humans; Male; Adolescent; Anorexia Nervosa; Fractures, Bone; Regression Analysis; Proportional Hazards Models; Minerals; Risk Factors
PubMed: 37578122
DOI: 10.1002/jbmr.4901 -
The Plant Genome Dec 2023Plant nutrition is an important aspect that contributes significantly to sustainable agriculture, whereas minerals enrichment in edible source implies global human... (Review)
Review
Plant nutrition is an important aspect that contributes significantly to sustainable agriculture, whereas minerals enrichment in edible source implies global human health; hence, both strategies need to be bridged to ensure "One Health" strategies. Abiotic stress-induced nutritional imbalance impairs plant growth. In this context, we discuss the molecular mechanisms related to the readjustment of nutrient pools for sustained plant growth under harsh conditions, and channeling the minerals to edible source (seeds) to address future nutritional security. This review particularly highlights interventions on (i) the physiological and molecular responses of mineral nutrients in crop plants under stressful environments; (ii) the deployment of breeding and biotechnological strategies for the optimization of nutrient acquisition, their transport, and distribution in plants under changing environments. Furthermore, the present review also infers the recent advancements in breeding and biotechnology-based biofortification approaches for nutrient enhancement in crop plants to optimize yield and grain mineral concentrations under control and stress-prone environments to address food and nutritional security.
Topics: Humans; Plant Breeding; Edible Grain; Minerals; Seeds; Nutrients
PubMed: 37480222
DOI: 10.1002/tpg2.20362 -
Environment International Oct 2023Studies on atmospheric dust and long-range transport of mineral dust have been a focus of atmospheric science in recent years. With its wide range of direct and indirect...
Studies on atmospheric dust and long-range transport of mineral dust have been a focus of atmospheric science in recent years. With its wide range of direct and indirect effects, mineral dust is one of the most uncertain elements in the mechanisms of climate change, and a deeper understanding of its role is essential for understanding future processes. The aim of our research was to provide the first systematic data on the so far episodically documented northward transport mineral dust from arid-semiarid areas. So, in this paper, we present dust storm events from lower latitudes reaching the Finnish atmosphere, based on the MERRA-2 model Dust Column Mass Density data and after a multistep verification procedure using independent data source. In total, 86 long-range dust storm events were identified between 1980 and 2022, when air masses loaded with dust reached Finland. Based on backward-trajectories different sources were identified: 59 were Saharan, 22 were Aral-Caspian, and five were associated with Middle Eastern source areas. Considerable variation in inter-annual frequencies was observed among the source areas, which may be due to changes in circulation conditions and the effects of human activity (agriculture and land use changes in Aral Sea region). There is a clear maximum of dust events in spring (60%), followed by summer and autumn (where 10 of the 11 autumn episodes were from the Sahara). However, the number and proportion of scarce winter events have more than doubled since 2010 compared to the preceding 30 years, but no autumn events were registered during this period. This clear temporal variation coincides with changes in dust transport observed in other regions of Europe, driven by greater atmospheric meridionality associated with climate change and driven by reduced temperature difference between low and high latitudes due to enhanced temperature increases at Arctic regions.
Topics: Humans; Dust; Finland; Air Pollutants; Environmental Monitoring; Africa, Northern; Middle East; Minerals
PubMed: 37804716
DOI: 10.1016/j.envint.2023.108243 -
Poultry Science Mar 2024The eggshell is the outermost covering of an egg that provides physical and chemical protection. It is a major source of calcium and minerals for the growing embryo...
The eggshell is the outermost covering of an egg that provides physical and chemical protection. It is a major source of calcium and minerals for the growing embryo during incubation. The egg industry suffers from a considerable economic loss due to poor eggshell quality. Therefore, developing an accurate and precise method of determining eggshell quality is crucial in improving eggshells in subsequent generations of breeding stock. Hence, this study aimed to develop a method to accurately and precisely determine 1) eggshell thickness using a scanning electron microscope (SEM) and 2) eggshell mineral components using an SEM-Energy Dispersive Spectrometry (EDS) system. Four types of table eggs (N = 48; 12 eggs/group): Cage-Free Organic from the US Mainland (CFO-M) and Hawaii (CFO-H), Caged Non-Organic from the US Mainland (CNO-M), and Hawaii (CNO-H) were sourced from the grocery store. Approximately 0.5 mm pieces of eggshells from the equator region of the egg were taken and processed for visualization under the SEM. Three distinct layers of eggshell were identified under SEM: the outermost cuticle, the middle palisade, and the innermost mammillary region. The results showed that CFO-H eggs have a greater eggshell thickness (380.43 ± 2.69 µm) and effective thickness (306.28 ± 4.15 µm). Similarly, the mammillary knob count was denser in CNO-H eggs (186 ± 23.02 knobs/0.5 mm). Calcium (97.36 ± 0.17%) was the highest among minerals in lower palisades (LP). The magnesium concentration was lowest in the LP region, whereas the phosphorus concentration was highest in the upper palisades. Our study established a scientific method to assess the eggshell quality and biochemical characteristics of eggs through SEM and EDS. This method can be used as a marker for selecting superior parent stock to improve eggshell quality in subsequent generations of breeding stock.
Topics: Animals; Calcium; Egg Shell; Microscopy, Electron, Scanning; Chickens; Ovum; Calcium, Dietary; Minerals
PubMed: 38301498
DOI: 10.1016/j.psj.2024.103428 -
Ciencia & Saude Coletiva Sep 2023The purpose of the present study was to estimate the prevalence of vitamin and/or mineral use among urban Brazilian populations aged 20 years and over and to identify...
The purpose of the present study was to estimate the prevalence of vitamin and/or mineral use among urban Brazilian populations aged 20 years and over and to identify associated factors. Data from the National Survey on Access, Use and Promotion of the Rational Use of Medicines in Brazil (PNAUM) were analyzed and a population-based cross-sectional study with probability sampling was performed in urban areas of Brazil's five geographic regions from September 2013 to February 2014. The estimated prevalence of vitamin and/or mineral use was 4.8% (95%CI: 4.3-5.3), higher in women 6.4% (95%CI: 5.7-7.1) and in the elderly population 11.6% (95%CI: 10.5-12.8). Vitamin and/or mineral use was associated with the following factors: women, 60 years of age or older, economic class A/B, chronic disease(s) and self-perceived health held as average and very poor/poor. Multivitamins and multiminerals were the most used ones with 24.5% (95%CI 20.1-29.4), followed by calcium and vitamin D with 23.4% (95%CI 19.7-27.5). Data suggest that elderly women should be the reference public for actions aimed at promoting rational use. Nationwide epidemiological surveys should increase monitoring of these products to support the analysis of trends.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Brazil; Cross-Sectional Studies; Minerals; Prevalence; Socioeconomic Factors; Urban Population; Vitamins; Young Adult
PubMed: 37672452
DOI: 10.1590/1413-81232023289.15032022 -
Journal of Bone and Mineral Research :... Dec 2023Osteoporosis and fractures severely impact the elderly population. Polygenic risk scores for bone mineral density have demonstrated potential clinical utility. However,...
Osteoporosis and fractures severely impact the elderly population. Polygenic risk scores for bone mineral density have demonstrated potential clinical utility. However, the value of rare genetic determinants in risk prediction has not been assessed. With whole-exome sequencing data from 436,824 UK Biobank participants, we assigned White British ancestry individuals into a training data set (n = 317,434) and a test data set (n = 74,825). In the training data set, we developed a common variant-based polygenic risk score for heel ultrasound speed of sound (SOS). Next, we performed burden testing to identify genes harboring rare determinants of bone mineral density, targeting influential rare variants with predicted high deleteriousness. We constructed a genetic risk score, called ggSOS, to incorporate influential rare variants in significant gene burden masks into the common variant-based polygenic risk score. We assessed the predictive performance of ggSOS in the White British test data set, as well as in populations of non-White British European (n = 18,885), African (n = 7165), East Asian (n = 2236), South Asian (n = 9829), and other admixed (n = 1481) ancestries. Twelve genes in pivotal regulatory pathways of bone homeostasis harbored influential rare variants associated with SOS (p < 5.5 × 10 ), including AHNAK, BMP5, CYP19A1, FAM20A, FBXW5, KDM5B, KREMEN1, LGR4, LRP5, SMAD6, SOST, and WNT1. Among 4013 (5.4%) individuals in the test data set carrying these variants, a one standard deviation decrease in ggSOS was associated with 1.35-fold (95% confidence interval [CI] 1.16-1.57) increased hazard of major osteoporotic fracture. However, compared with a common variant-based polygenic risk score (C-index = 0.641), ggSOS had only marginally improved prediction accuracy in identifying at-risk individuals (C-index = 0.644), with overlapping confidence intervals. Similarly, ggSOS did not demonstrate substantially improved predictive performance in non-European ancestry populations. In summary, modeling the effects of rare genetic determinants may assist polygenic prediction of fracture risk among carriers of influential rare variants. Nonetheless, improved clinical utility is not guaranteed for population-level risk screening. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Aged; Bone Density; Genetic Predisposition to Disease; Osteoporosis; Osteoporotic Fractures; Genetic Risk Score; Minerals
PubMed: 37830501
DOI: 10.1002/jbmr.4920 -
Food Research International (Ottawa,... Nov 2023Seeds of the species Acacia retinodes, A. provincialis, and A. tenuissima) from different growing locations were analysed for their mineral composition, free and bound...
Seeds of the species Acacia retinodes, A. provincialis, and A. tenuissima) from different growing locations were analysed for their mineral composition, free and bound polyphenols, and flavonoids. Previous research has studied these compounds in only a limited number of Acacia species, and only one study reports significant differences between three species. All species were rich in potassium (353 - 427 mg/100 g), sodium (14 - 240 mg/100 g) and iron (7 - 8 mg/100 g). The free polyphenol extracts of all species had higher total phenolic content, total flavonoid content and antioxidant activities than their bound counterparts, indicating the possibility of higher bioavailability than the bound polyphenol extracts. The predominant phenolic compounds found in the Acacia polyphenol seed extracts were 6-Hydroxy-2-methylindole and 2,2'-Methylenebis(6-tert-butyl-methylphenol), though no phenolic compounds were identified in the bound extracts of A. retinodes Grampians and A. provincialis Tarrington. Other compounds identified in the seed extracts include sucrose, d-fructofuranose and d-pinitol.
Topics: Antioxidants; Acacia; Plant Extracts; Phenols; Polyphenols; Flavonoids; Seeds; Minerals
PubMed: 37803777
DOI: 10.1016/j.foodres.2023.113452