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1.
Plant-based diets and bone health: sorting through the evidence.
Hsu, E
Current opinion in endocrinology, diabetes, and obesity. 2020;(4):248-252
Abstract
PURPOSE OF REVIEW An increase in awareness of vegetarian and vegan (plant-based) diets has brought forth numerous studies on their effects on health. The study of nutrition-based factors affecting bone health is difficult, given the length of time before clinical effects are evident. Furthermore, population-based studies must account for strong confounding influences as effects may be because of association, not causality. Yet, it is highly plausible that dietary factors affect bone remodeling in multiple ways. Plant-based diets may alter macronutrient and micronutrient balance, may cause differences in prebiotic and probiotic effects on gut microbiota, and may subtly change the inflammatory and immune response. RECENT FINDINGS Several recent studies have looked at plant-based nutrition and markers of bone health, using measures such as bone turnover markers, bone mineral density, or fracture rates. Although population based and cross-sectional studies can be prone to confounding effects, a majority did not show differences in bone health between vegetarians/vegans and omnivores as long as calcium and vitamin D intake were adequate. A few prospective cohort or longitudinal studies even demonstrate some benefit to a plant-based diet, but this claim remains unproven. SUMMARY There is no evidence that a plant-based diet, when carefully chosen to maintain adequate calcium and vitamin D levels, has any detrimental effects on bone health. Theoretical findings suggest a long-term plant-based diet may reduce the risk of osteoporosis, through mechanisms that are currently speculative.
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2.
Δ1 -Pyrroline-5-carboxylate synthetase deficiency: An emergent multifaceted urea cycle-related disorder.
Marco-Marín, C, Escamilla-Honrubia, JM, Llácer, JL, Seri, M, Panza, E, Rubio, V
Journal of inherited metabolic disease. 2020;(4):657-670
Abstract
The bifunctional homooligomeric enzyme Δ1 -pyrroline-5-carboxylate synthetase (P5CS) and its encoding gene ALDH18A1 were associated with disease in 1998. Two siblings who presented paradoxical hyperammonemia (alleviated by protein), mental disability, short stature, cataracts, cutis laxa, and joint laxity, were found to carry biallelic ALDH18A1 mutations. They showed biochemical indications of decreased ornithine/proline synthesis, agreeing with the role of P5CS in the biosynthesis of these amino acids. Of 32 patients reported with this neurocutaneous syndrome, 21 familial ones hosted homozygous or compound heterozygous ALDH18A1 mutations, while 11 sporadic ones carried de novo heterozygous ALDH18A1 mutations. In 2015 to 2016, an upper motor neuron syndrome (spastic paraparesis/paraplegia SPG9) complicated with some traits of the neurocutaneous syndrome, although without report of cutis laxa, joint laxity, or herniae, was associated with monoallelic or biallelic ALDH18A1 mutations with, respectively, dominant and recessive inheritance. Of 50 SPG9 patients reported, 14 and 36 (34/2 familial/sporadic) carried, respectively, biallelic and monoallelic mutations. Thus, two neurocutaneous syndromes (recessive and dominant cutis laxa 3, abbreviated ARCL3A and ADCL3, respectively) and two SPG9 syndromes (recessive SPG9B and dominant SPG9A) are caused by essentially different spectra of ALDH18A1 mutations. On the bases of the clinical data (including our own prior patients' reports), the ALDH18A1 mutations spectra, and our knowledge on the P5CS protein, we conclude that the four syndromes share the same pathogenic mechanisms based on decreased P5CS function. Thus, these syndromes represent a continuum of increasing severity (SPG9A < SPG9B < ADCL3 ≤ ARCL3A) of the same disease, P5CS deficiency, in which the dominant mutations cause loss-of-function by dominant-negative mechanisms.
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3.
Mineral and bone physiology in the foetus, preterm and full-term neonates.
Sethi, A, Priyadarshi, M, Agarwal, R
Seminars in fetal & neonatal medicine. 2020;(1):101076
Abstract
Mother is the major source of minerals in foetal life with placenta actively transporting against a concentration and electrochemical gradient. The foetal serum mineral concentration is thereby higher as compared to maternal values, which possibly help in its rapid accretion in developing bones and for counteracting postnatal fall in calcium levels at birth. Parathyroid hormone related peptide (PTHrP) and parathyroid hormone (PTH) play a major role in mineral physiology during foetal life with hormones like calcitriol, calcitonin, FGF-23 and sex steroids having minimal role. PTHrP and PTH also play a major role in endochondral bone formation and mineralization of skeleton. At the birth, as the cord is clamped, there is loss of active transport of minerals through placenta and the neonate has to rely on enteral intake of minerals to meet the demands of growing bones and metabolisms. The calcium levels fall after birth, reaching a nadir at 24-48 h and gradually rise to adult values over several days, probably resulting from a fall in PTHrP levels and hyporesponsiveness of parathyroid glands. As PTH and calcitriol levels increase postnatally, there is a rise in calcium levels with maturation in functioning of kidneys and intestines. However, there may be significant delay in intestinal maturation in preterm infants along with an increased demand for mineral accretion, which predispose them to osteopenia of prematurity.
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4.
Perlecan, a modular instructive proteoglycan with diverse functional properties.
Melrose, J
The international journal of biochemistry & cell biology. 2020;:105849
Abstract
This study reviewed some new aspects of the modular proteoglycan perlecan, a colossal proteoglycan with a 467 kDa core protein and five distinct functional domains. Perlecan is a heparan sulphate proteoglycan that transiently displays native CS sulphation motifs 4-C-3 and 7-D-4 during tissue morphogenesis these are expressed by progenitor cell populations during tissue development. Perlecan is susceptible to fragmentation by proteases during tissue development and in pathological tissues particularly in domains IV and V. The fragmentation pattern of domain IV has been suggested as a means of grading prostate cancer. Domain V of perlecan is of interest due to its interactive properties with integrin α5β1 that promotes pericyte migration enhancing PDGF-BB-induced phosphorylation of PDGFRβ, Src homology region 2 domain-containing phosphatase-2, and focal adhesion kinase supporting the repair of the blood brain barrier following ischaemic stroke. Fragments of domain V can also interact with α2β1 integrin disrupting tube formation by endothelial cells. LG1-LG2, LG3 fragments can antagonise VEGFR2, and α2β1 integrin interactions preventing angiogenesis by endothelial cells. These domain V fragments are of interest as potential anti-tumour agents. Perlecan attached to the luminal surfaces of endothelial cells in blood vessels acts as a flow sensor that signals back to endothelial and smooth muscle cells to regulate vascular tone and blood pressure. Perlecan also acts as a flow sensor in the lacuno-canalicular space regulating osteocytes and bone homeostasis. Along with its biomechanical regulatory properties in cartilaginous tissues this further extends the functional repertoire of this amazingly diverse functional proteoglycan.
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5.
RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling.
Tobeiha, M, Moghadasian, MH, Amin, N, Jafarnejad, S
BioMed research international. 2020;:6910312
Abstract
Bones as an alive organ consist of about 70% mineral and 30% organic component. About 200 million people are suffering from osteopenia and osteoporosis around the world. There are multiple ways of protecting bone from endogenous and exogenous risk factors. Planned physical activity is another useful way for protecting bone health. It has been investigated that arranged exercise would effectively regulate bone metabolism. Until now, a number of systems have discovered how exercise could help bone health. Previous studies reported different mechanisms of the effect of exercise on bone health by modulation of bone remodeling. However, the regulation of RANKL/RANK/OPG pathway in exercise and physical performance as one of the most important remodeling systems is not considered comprehensive in previous evidence. Therefore, the aim of this review is to clarify exercise influence on bone modeling and remodeling, with a concentration on its role in regulating RANKL/RANK/OPG pathway.
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6.
Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors.
Altieri, B, Di Dato, C, Modica, R, Bottiglieri, F, Di Sarno, A, Pittaway, JFH, Martini, C, Faggiano, A, Colao, A
Nutrients. 2020;(4)
Abstract
Patients affected by gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP-NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP-NET, focusing on vitamin D and its role in GEP-NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.
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7.
Post-natal bone physiology.
El-Farrash, RA, Ali, RH, Barakat, NM
Seminars in fetal & neonatal medicine. 2020;(1):101077
Abstract
Post-natal bone development is characterized by substantial longitudinal bone growth and changes in skeletal size and shape. Bone is in a dynamic process of continuous remodeling which helps to regulate calcium homeostasis, repair micro-damage to bones from everyday stress, and to shape the skeleton during growth. Bone growth is regulated by systemic hormones and locally generated factors. Understanding their mechanisms of action enables us to obtain a better appreciation of the cellular and molecular basis of bone remodeling and could therefore be valuable in approaches to new therapies. This article will review molecular and cellular control of skeletal growth in the post-natal period, the physiology of each bone cell with their systemic and local regulators, as well as the physiology of bone remodeling.
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8.
The osteocyte: A multifunctional cell within the bone.
Tresguerres, FGF, Torres, J, López-Quiles, J, Hernández, G, Vega, JA, Tresguerres, IF
Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft. 2020;:151422
Abstract
The knowledge of bone biology has largely changed in the last few decades. Osteocytes are multifunctional bone cells that are surrounded by mineralized bone matrix and for decades it was considered that they might be relatively inactive cells. However, nowadays it is known that osteocytes are highly active cells which are indispensable for the normal function of the skeleton, playing main roles in several physiological processes, both within and beyond the bone microenvironment. This review highlights and updates the current state of knowledge of the osteocyte and focuses on its roles in bone remodeling and mineral homeostasis, and also reviews its recently discovered endocrine function. Osteocytes secrete sclerostin (a protein that works as a negative regulator of bone mass), and FGF-23, the most important osteocyte-secreted endocrine factor, since it is able to regulate the phosphate metabolism. Moreover, osteocytes can act as mechanosensory cells, transforming the mechanical strain into chemical signaling towards the effector cells (osteoblasts and osteoclasts). Therefore, the osteocyte plays an important role in bone biology, specifically in the remodeling process, since it regulates both the osteoblast and osteoclast activity. Finally, the paper discusses the clinical application of the bone biology, updating the new therapies against bone-loss disorders.
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9.
Adverse effects of androgen deprivation therapy in patients with prostate cancer: Focus on muscle and bone health.
Bargiota, A, Oeconomou, A, Zachos, I, Samarinas, M, L Pisters, L, Tzortzis, V
Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2020;(3):1286-1294
Abstract
Androgen deprivation therapy (ADT) is the most effective systemic treatment for prostate cancer and can be succeeded either surgically or pharmaceutically. Both approaches lead to hypogonadism with a large variety of adverse events, including obesity, metabolic syndrome, osteoporosis, sarcopenia, diabetes mellitus, cardiovascular disease, gynecomastia and sexual dysfunction. In addition, undesirable effects on muscle and bone health may have a significant impact not only on the quality of life but also on life expectancy. Currently, supervised exercise seems to be the only intervention that could prevent the adverse effects of the ADT and improve quality of life. Lifestyle modification, supplementation of calcium, vitamin D and when indicated antiosteoporotic treatments improve bone health. However, patients receiving ADT must be well informed about the potential benefits as well as the risks of the treatment.
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10.
Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging.
Serna, J, Bergwitz, C
Nutrients. 2020;(10)
Abstract
Inorganic phosphate (Pi) plays a critical function in many tissues of the body: for example, as part of the hydroxyapatite in the skeleton and as a substrate for ATP synthesis. Pi is the main source of dietary phosphorus. Reduced bioavailability of Pi or excessive losses in the urine causes rickets and osteomalacia. While critical for health in normal amounts, dietary phosphorus is plentiful in the Western diet and is often added to foods as a preservative. This abundance of phosphorus may reduce longevity due to metabolic changes and tissue calcifications. In this review, we examine how dietary phosphorus is absorbed in the gut, current knowledge about Pi sensing, and endocrine regulation of Pi levels. Moreover, we also examine the roles of Pi in different tissues, the consequences of low and high dietary phosphorus in these tissues, and the implications for healthy aging.