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Journal of Bone and Mineral Research :... Oct 2023Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy... (Randomized Controlled Trial)
Randomized Controlled Trial
Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy and safety of the abaloparatide microstructured transdermal system (abaloparatide-sMTS) as an alternative to the SC formulation. This phase 3, noninferiority study (NCT04064411) randomly assigned postmenopausal women with osteoporosis (N = 511) 1:1 to open-label abaloparatide administered daily via abaloparatide-sMTS or SC injection for 12 months. The primary comparison between treatment groups was the percentage change in lumbar spine bone mineral density (BMD) at 12 months, with a noninferiority margin of 2.0%. Secondary endpoints included percentage change in total hip and femoral neck BMD, bone turnover markers, dermatologic safety, and new clinical fracture incidence. At 12 months, percentage increase from baseline in lumbar spine BMD was 7.14% (SE: 0.46%) for abaloparatide-sMTS and 10.86% (SE: 0.48%) for abaloparatide-SC (treatment difference: -3.72% [95% confidence interval: -5.01%, -2.43%]). Percentage change in total hip BMD was 1.97% for abaloparatide-sMTS and 3.70% for abaloparatide-SC. Median changes from baseline at 12 months in serum procollagen type I N-terminal propeptide (s-PINP) were 52.6% for abaloparatide-sMTS and 74.5% for abaloparatide-SC. Administration site reactions were the most frequently reported adverse events (abaloparatide-sMTS, 94.4%; abaloparatide-SC, 70.5%). Incidence of serious adverse events was similar between groups. Mild or moderate skin reactions occurred with abaloparatide-sMTS with no identifiable risk factors for sensitization reactions. Few new clinical fractures occurred in either group. Noninferiority of abaloparatide-sMTS to abaloparatide-SC for percentage change in spine BMD at 12 months was not demonstrated; however, clinically meaningful increases from baseline in lumbar spine and total hip BMD were observed in both treatment groups. © 2023 Radius Health, Inc and 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; Female; Osteoporosis, Postmenopausal; Bone Density Conservation Agents; Postmenopause; Osteoporosis; Bone Density; Osteoporotic Fractures; Lumbar Vertebrae; Minerals
PubMed: 37417725
DOI: 10.1002/jbmr.4877 -
PloS One 2023Data on mineral digestibility is key to understand mineral homeostasis and refine the recommendations for the dietary intake of these nutrients. In farm animals and...
Data on mineral digestibility is key to understand mineral homeostasis and refine the recommendations for the dietary intake of these nutrients. In farm animals and pets, there is plenty of data on mineral digestibility and influencing factors. In laboratory mice, however, there is a lack of information on mineral digestibility under maintenance conditions, although this should be the basis for studies on mineral homeostasis under experimental conditions. The aim of the present study was to analyse data on intake, faecal excretion, and apparent digestibility of calcium, phosphorus, sodium, potassium, and magnesium in C57BL/6J mice fed different maintenance diets with varying voluntary dry matter intake. Lucas-tests were used to quantify true digestibility and describe correlations between dietary intake and excretion/absorption of the nutrients. Calcium, phosphorus, and magnesium showed a linear correlation between intake and faecal excretion (R2: 0.77, 0.93 and 0.91, respectively). Intake and apparently digested amounts of sodium and potassium were correlated linearly (R2: 0.86 and 0.98, respectively). These data show that intake is the major determinant of absorption in the minerals listed above. Faecal calcium and phosphorus excretion were correlated as well (R2 = 0.75).
Topics: Animals; Mice; Calcium; Magnesium; Mice, Inbred C57BL; Digestion; Minerals; Phosphorus; Calcium, Dietary; Diet; Sodium; Potassium; Animal Feed
PubMed: 37585435
DOI: 10.1371/journal.pone.0290145 -
International Journal of Molecular... Jul 2023Endothelial-mesenchymal transition (EndMT) drives endothelium to contribute to atherosclerotic calcification. In a previous study, we showed that glycogen synthase...
Endothelial-mesenchymal transition (EndMT) drives endothelium to contribute to atherosclerotic calcification. In a previous study, we showed that glycogen synthase kinase-3β (GSK3β) inhibition induced β-catenin and reduced mothers against DPP homolog 1 (SMAD1) in order to redirect osteoblast-like cells towards endothelial lineage, thereby reducing vascular calcification in deficiency and diabetic mice. Here, we report that GSK3β inhibition or endothelial-specific deletion of GSK3β reduces atherosclerotic calcification. We also find that alterations in β-catenin and SMAD1 induced by GSK3β inhibition in the aortas of mice are similar to mice. Together, our results suggest that GSK3β inhibition reduces vascular calcification in atherosclerotic lesions through a similar mechanism to that in mice.
Topics: Animals; Mice; Atherosclerosis; beta Catenin; Calcification, Physiologic; Glycogen Synthase Kinase 3 beta; Vascular Calcification
PubMed: 37511396
DOI: 10.3390/ijms241411638 -
Journal of Immunology Research 2023Sufficient mineral supply is vital not only for the innate immune system but also for the components of the adaptive immune defense, which encompass defense mechanisms... (Review)
Review
Sufficient mineral supply is vital not only for the innate immune system but also for the components of the adaptive immune defense, which encompass defense mechanisms against pathogens and the delicate balance of pro- and anti-inflammatory regulation in the long term. Generally, a well-balanced diet is capable of providing the necessary minerals to support the immune system. Nevertheless, specific vulnerable populations should be cautious about obtaining adequate amounts of minerals such as magnesium, zinc, copper, iron, and selenium. Inadequate levels of these minerals can temporarily impair immune competence and disrupt the long-term regulation of systemic inflammation. Therefore, comprehending the mechanisms and sources of these minerals is crucial. In exceptional circumstances, mineral deficiencies may necessitate supplementation; however, excessive intake of supplements can have adverse effects on the immune system and should be avoided. Consequently, any supplementation should be approved by medical professionals and administered in recommended doses. This review emphasizes the crucial significance of minerals in promoting optimal functioning of the immune system. It investigates the indispensable minerals required for immune system function and the regulation of inflammation. Moreover, it delves into the significance of maintaining an optimized intake of minerals from a nutritional standpoint.
Topics: Humans; Dietary Supplements; Zinc; Selenium; Inflammation; Immunity
PubMed: 37946846
DOI: 10.1155/2023/3355733 -
Bone Research Nov 2023Matrix vesicles (MVs) have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the...
Matrix vesicles (MVs) have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the skeletal system due to their membranous vesicle characteristics and abundant calcium and phosphorus content. However, the role of MVs in the progression of osteoporosis is poorly understood. Here, we report that annexin A5, an important component of the matrix vesicle membrane, plays a vital role in bone matrix homeostasis in the deterioration of osteoporosis. We first identified annexin A5 from adherent MVs but not dissociative MVs of osteoblasts and found that it could be sharply decreased in the bone matrix during the occurrence of osteoporosis based on ovariectomized mice. We then confirmed its potential in mediating the mineralization of the precursor osteoblast lineage via its initial binding with collagen type I to achieve MV adhesion and the subsequent activation of cellular autophagy. Finally, we proved its protective role in resisting bone loss by applying it to osteoporotic mice. Taken together, these data revealed the importance of annexin A5, originating from adherent MVs of osteoblasts, in bone matrix remodeling of osteoporosis and provided a new strategy for the treatment and intervention of bone loss.
Topics: Animals; Mice; Annexin A5; Calcification, Physiologic; Bone Matrix; Vascular Calcification; Bone Diseases, Metabolic; Osteoporosis
PubMed: 37940665
DOI: 10.1038/s41413-023-00290-9 -
Journal of Bone and Mineral Research :... Dec 2023Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is...
Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is unknown. We investigated the association of bone health (bone mineral density [BMD] and bone turnover markers) with incident type-2 diabetes mellitus (T2DM) based on the Hong Kong Osteoporosis Study (HKOS). A total of 993 and 7160 participants from the HKOS were studied for the cross-sectional and prospective analyses, respectively. The cross-sectional study evaluated the association of BMD and bone biomarkers with fasting glucose and glycated hemoglobin (Hb ) levels, whereas the prospective study examined the associations between BMD at study sites and the risk of T2DM by following subjects a median of 16.8 years. Body mass index (BMI) was adjusted in all full models. Mendelian randomization (MR) was conducted for causal inference. In the cross-sectional analysis, lower levels of circulating bone turnover markers and higher BMD were significantly associated with increased fasting glucose and Hb levels. In the prospective analysis, higher BMD (0.1 g/cm ) at the femoral neck and total hip was associated with increased risk of T2DM with hazard ratios (HRs) of 1.10 (95% confidence interval [CI], 1.03 to 1.18) and 1.14 (95% CI, 1.08 to 1.21), respectively. The presence of osteoporosis was associated with a 30% reduction in risk of T2DM compared to those with normal BMD (HR = 0.70; 95% CI, 0.55 to 0.90). The MR results indicate a robust genetic causal association of estimated BMD (eBMD) with 2-h glucose level after an oral glucose challenge test (estimate = 0.043; 95% CI, 0.007 to 0.079) and T2DM (odds ratio = 1.064; 95% CI, 1.036 to 1.093). Higher BMD and lower levels of circulating bone biomarkers were cross-sectionally associated with poor glycemic control. Moreover, higher BMD was associated with a higher risk of incident T2DM and the association is probably causal. © 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; Bone Density; Cross-Sectional Studies; Hong Kong; Glycated Hemoglobin; Mendelian Randomization Analysis; Prospective Studies; Osteoporosis; Diabetes Mellitus, Type 2; Glucose; Femur Neck; Biomarkers; Bone Remodeling; Minerals
PubMed: 37850799
DOI: 10.1002/jbmr.4924 -
JCI Insight Dec 2023Fibroblast growth factor 23 (FGF23) is a phosphate-regulating (Pi-regulating) hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23...
Fibroblast growth factor 23 (FGF23) is a phosphate-regulating (Pi-regulating) hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23 excess, impaired skeletal growth, and osteomalacia. Blocking FGF23 became an effective therapeutic strategy in X-linked hypophosphatemia, but testing remains limited in autosomal recessive hypophosphatemic rickets (ARHR). This study investigates the effects of Pi repletion and bone-specific deletion of Fgf23 on bone and mineral metabolism in the dentin matrix protein 1-knockout (Dmp1KO) mouse model of ARHR. At 12 weeks, Dmp1KO mice showed increased serum FGF23 and parathyroid hormone levels, hypophosphatemia, impaired growth, rickets, and osteomalacia. Six weeks of dietary Pi supplementation exacerbated FGF23 production, hyperparathyroidism, renal Pi excretion, and osteomalacia. In contrast, osteocyte-specific deletion of Fgf23 resulted in a partial correction of FGF23 excess, which was sufficient to fully restore serum Pi levels but only partially corrected the bone phenotype. In vitro, we show that FGF23 directly impaired osteoprogenitors' differentiation and that DMP1 deficiency contributed to impaired mineralization independent of FGF23 or Pi levels. In conclusion, FGF23-induced hypophosphatemia is only partially responsible for the bone defects observed in Dmp1KO mice. Our data suggest that combined DMP1 repletion and FGF23 blockade could effectively correct ARHR-associated mineral and bone disorders.
Topics: Animals; Mice; Calcification, Physiologic; Extracellular Matrix Proteins; Familial Hypophosphatemic Rickets; Fibroblast Growth Factors; Hypophosphatemia; Mice, Knockout; Minerals; Osteomalacia
PubMed: 37943605
DOI: 10.1172/jci.insight.156850 -
Nutrients Jul 2023Taro () is a root crop that remains largely underutilized and undervalued despite its abundance and affordability. In comparison to other root vegetables, such as... (Review)
Review
Taro () is a root crop that remains largely underutilized and undervalued despite its abundance and affordability. In comparison to other root vegetables, such as potatoes, yams, carrots, and cassava, taro stands out as a plentiful and low-cost option. As global hunger increases, particularly in Africa, it becomes essential to address food insecurity by maximizing the potential of existing food resources, including taro, and developing improved food products derived from it. Taro possesses a wealth of carbohydrates, dietary fiber, vitamins, and minerals, thereby making it a valuable nutritional source. Additionally, while not a significant protein source, taro exhibits higher protein content than many other root crops. Consequently, utilizing taro to create food products, such as plant-based milk alternatives, frozen desserts, and yogurt substitutes, could play a crucial role in raising awareness and increasing taro production. Unfortunately, taro has been stigmatized in various cultures, which has led to its neglect as a food crop. Therefore, this review aims to highlight the substantial potential of taro as an economical source of dietary energy by exploring the rich fiber, potassium, vitamin C, protein, and other micronutrient content of taro, and providing a foundation for the formulation of novel food products. Furthermore, this paper assesses the nutritional benefits of taro, its current utilization, and its antinutritional properties. It emphasizes the need for further research to explore the various applications of taro and improve on-farm processing conditions for industrial purposes.
Topics: Colocasia; Vitamins; Minerals; Crops, Agricultural; Micronutrients
PubMed: 37571276
DOI: 10.3390/nu15153337 -
Journal of Bone and Mineral Research :... Nov 2023Neurogenic heterotopic ossifications (NHO) are heterotopic bones that develop in periarticular muscles after severe central nervous system (CNS) injuries. Several...
Neurogenic heterotopic ossifications (NHO) are heterotopic bones that develop in periarticular muscles after severe central nervous system (CNS) injuries. Several retrospective studies have shown that NHO prevalence is higher in patients who suffer concomitant infections. However, it is unclear whether these infections directly contribute to NHO development or reflect the immunodepression observed in patients with CNS injury. Using our mouse model of NHO induced by spinal cord injury (SCI) between vertebrae T to T , we demonstrate that lipopolysaccharides (LPS) from gram-negative bacteria exacerbate NHO development in a toll-like receptor-4 (TLR4)-dependent manner, signaling through the TIR-domain-containing adapter-inducing interferon-β (TRIF/TICAM1) adaptor rather than the myeloid differentiation primary response-88 (MYD88) adaptor. We find that T to T SCI did not significantly alter intestinal integrity nor cause intestinal bacteria translocation or endotoxemia, suggesting that NHO development is not driven by endotoxins from the gut in this model of SCI-induced NHO. Relevant to the human pathology, LPS increased expression of osteoblast markers in cultures of human fibro-adipogenic progenitors isolated from muscles surrounding NHO biopsies. In a case-control retrospective study in patients with traumatic brain injuries, infections with gram-negative Pseudomonas species were significantly associated with NHO development. Together these data suggest a functional association between gram-negative bacterial infections and NHO development and highlights infection management as a key consideration to avoid NHO development in patients. © 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: Mice; Animals; Humans; Lipopolysaccharides; Retrospective Studies; Spinal Cord Injuries; Ossification, Heterotopic; Bacteria; Minerals
PubMed: 37602772
DOI: 10.1002/jbmr.4905 -
Nutrients Jul 2023The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a...
The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = -0.113%, standard error (SE) = 0.03%, -value = 2 × 10; glucosamine, eGFR change beta = -0.240%, SE = 0.035%, -value = 6 × 10). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, -value = 1 × 10). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.
Topics: Vitamins; Glucosamine; Mendelian Randomization Analysis; Genome-Wide Association Study; Chondroitin; Polymorphism, Single Nucleotide; Kidney; Minerals
PubMed: 37571255
DOI: 10.3390/nu15153318