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1.
Acute catabolic bone metabolism response to exercise in young and older adults: A narrative review.
Wherry, SJ, Swanson, CM, Kohrt, WM
Experimental gerontology. 2022;:111633
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Abstract
Exercise is recommended for cardiometabolic benefits and to preserve or improve bone health, especially for older adults at increased risk of fracture. However, exercise interventions have modest benefits on areal bone mineral density (aBMD), and exercise can lead to bone loss in young athletes under certain conditions. In this narrative review, we discuss evidence for a disruption in calcium homeostasis during exercise that may diminish the skeletal benefits of exercise. Topics include 1) a general overview of the effects of exercise on aBMD; 2) discussion of the exercise-induced disruption in calcium homeostasis; 3) factors that influence the magnitude of the exercise-induced disruption in calcium homeostasis, including age, sex, and exercise mode, intensity, and duration; 4) oral calcium supplementation to minimize the exercise-induced disruption in calcium homeostasis; and 5) potential for exercise-induced increase in parathyroid hormone to be both catabolic and anabolic to bone.
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Muscle and Bone Impairment in Infantile Nephropathic Cystinosis: New Concepts.
Haffner, D, Leifheit-Nestler, M, Alioli, C, Bacchetta, J
Cells. 2022;(1)
Abstract
Cystinosis Metabolic Bone Disease (CMBD) has emerged during the last decade as a well-recognized, long-term complication in patients suffering from infantile nephropathic cystinosis (INC), resulting in significant morbidity and impaired quality of life in teenagers and adults with INC. Its underlying pathophysiology is complex and multifactorial, associating complementary, albeit distinct entities, in addition to ordinary mineral and bone disorders observed in other types of chronic kidney disease. Amongst these long-term consequences are renal Fanconi syndrome, hypophosphatemic rickets, malnutrition, hormonal abnormalities, muscular impairment, and intrinsic cellular bone defects in bone cells, due to CTNS mutations. Recent research data in the field have demonstrated abnormal mineral regulation, intrinsic bone defects, cysteamine toxicity, muscle wasting and, likely interleukin-1-driven inflammation in the setting of CMBD. Here we summarize these new pathophysiological deregulations and discuss the crucial interplay between bone and muscle in INC. In future, vitamin D and/or biotherapies targeting the IL1β pathway may improve muscle wasting and subsequently CMBD, but this remains to be proven.
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High resolution 3D structures of mineralized tissues in health and disease.
Weiner, S, Raguin, E, Shahar, R
Nature reviews. Endocrinology. 2021;(5):307-316
Abstract
A thorough knowledge of the structures of healthy mineralized tissues, such as bone or cartilage, is key to understanding the pathological changes occurring during disease. Such knowledge enables the underlying mechanisms that are responsible for pathology to be pinpointed. One high-resolution 3D method in particular - focused ion beam-scanning electron microscopy (FIB-SEM) - has fundamentally changed our understanding of healthy vertebrate mineralized tissues. FIB-SEM can be used to study demineralized matrix, the hydrated components of tissue (including cells) using cryo-fixation and even untreated mineralized tissue. The latter requires minimal sample preparation, making it possible to study enough samples to carry out studies capable of detecting statistically significant differences - a pre-requisite for the study of pathological tissues. Here, we present an imaging and characterization strategy for tissue structures at different length scales, describe new insights obtained on healthy mineralized tissues using FIB-SEM, and suggest future research directions for both healthy and diseased mineralized tissues.
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4.
The Role of Diet in Bone and Mineral Metabolism and Secondary Hyperparathyroidism.
Bargagli, M, Arena, M, Naticchia, A, Gambaro, G, Mazzaferro, S, Fuster, D, Ferraro, PM
Nutrients. 2021;(7)
Abstract
Bone disorders are a common complication of chronic kidney disease (CKD), obesity and gut malabsorption. Secondary hyperparathyroidism (SHPT) is defined as an appropriate increase in parathyroid hormone (PTH) secretion, driven by either reduced serum calcium or increased phosphate concentrations, due to an underlying condition. The available evidence on the effects of dietary advice on secondary hyperparathyroidism confirms the benefit of a diet characterized by decreased phosphate intake, avoiding low calcium and vitamin D consumption (recommended intakes 1000-1200 mg/day and 400-800 UI/day, respectively). In addition, low protein intake in CKD patients is associated with a better control of SHPT risk factors, although its strength in avoiding hyperphosphatemia and the resulting outcomes are debated, mostly for dialyzed patients. Ultimately, a consensus on the effect of dietary acid loads in the prevention of SHPT is still lacking. In conclusion, a reasonable approach for reducing the risk for secondary hyperparathyroidism is to individualize dietary manipulation based on existing risk factors and concomitant medical conditions. More studies are needed to evaluate long-term outcomes of a balanced diet on the management and prevention of secondary hyperparathyroidism in at-risk patients at.
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5.
Role of Phosphate in Biomineralization.
Bhadada, SK, Rao, SD
Calcified tissue international. 2021;(1):32-40
Abstract
Inorganic phosphate is a vital constituent of cells and cell membranes, body fluids, and hard tissues. It is a major intracellular divalent anion, participates in many genetic, energy and intermediary metabolic pathways, and is important for bone health. Although we usually think of phosphate mostly in terms of its level in the serum, it is needed for many biological and structural functions of the body. Availability of adequate calcium and inorganic phosphate in the right proportions at the right place is essential for proper acquisition, biomineralization, and maintenance of mass and strength of the skeleton. The three specialized mineralized tissues, bones, teeth, and ossicles, differ from all other tissues in the human body because of their unique ability to mineralize, and the degree and process of mineralization in these tissues also differ to suit the specific functions: locomotion, chewing, and hearing, respectively. Biomineralization is a dynamic, complex, and lifelong process by which precipitations of inorganic calcium and inorganic phosphate divalent ions form biological hard tissues. Understanding the biomineralization process is important for the management of diseases caused by both defective and abnormal mineralization. Hypophosphatemia results in mineralization defects and osteomalacia, and hyperphosphatemia is implicated in abnormal excess calcification and/or ossification, but the exact mechanisms underlying these processes are not fully understood. In this review, we summarize available evidence on the role of phosphate in biomineralization. Other manuscripts in this issue of the journal deal with other relevant aspects of phosphate homeostasis, phosphate signaling and sensing, and disorders resulting from hypo- and hyperphosphatemic states.
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6.
Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications.
Emmanuelle, NE, Marie-Cécile, V, Florence, T, Jean-François, A, Françoise, L, Coralie, F, Alexia, V
International journal of molecular sciences. 2021;(4)
Abstract
Bone is a multi-skilled tissue, protecting major organs, regulating calcium phosphate balance and producing hormones. Its development during childhood determines height and stature as well as resistance against fracture in advanced age. Estrogens are key regulators of bone turnover in both females and males. These hormones play a major role in longitudinal and width growth throughout puberty as well as in the regulation of bone turnover. In women, estrogen deficiency is one of the major causes of postmenopausal osteoporosis. In this review, we will summarize the main clinical and experimental studies reporting the effects of estrogens not only in females but also in males, during different life stages. Effects of estrogens on bone involve either Estrogen Receptor (ER)α or ERβ depending on the type of bone (femur, vertebrae, tibia, mandible), the compartment (trabecular or cortical), cell types involved (osteoclasts, osteoblasts and osteocytes) and sex. Finally, we will discuss new ongoing strategies to increase the benefit/risk ratio of the hormonal treatment of menopause.
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7.
The Effect of Space Travel on Bone Metabolism: Considerations on Today's Major Challenges and Advances in Pharmacology.
Genah, S, Monici, M, Morbidelli, L
International journal of molecular sciences. 2021;(9)
Abstract
Microgravity-induced bone loss is currently a significant and unresolved health risk for space travelers, as it raises the likelihood for irreversible changes that weaken skeletal integrity and the incremental onset of fracture injuries and renal stone formation. Another issue related to bone tissue homeostasis in microgravity is its capacity to regenerate following fractures due to weakening of the tissue and accidental events during the accomplishment of particularly dangerous tasks. Today, several pharmacological and non-pharmacological countermeasures to this problem have been proposed, including physical exercise, diet supplements and administration of antiresorptive or anabolic drugs. However, each class of pharmacological agents presents several limitations as their prolonged and repeated employment is not exempt from the onset of serious side effects, which limit their use within a well-defined range of time. In this review, we will focus on the various countermeasures currently in place or proposed to address bone loss in conditions of microgravity, analyzing in detail the advantages and disadvantages of each option from a pharmacological point of view. Finally, we take stock of the situation in the currently available literature concerning bone loss and fracture healing processes. We try to understand which are the critical points and challenges that need to be addressed to reach innovative and targeted therapies to be used both in space missions and on Earth.
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8.
Vitamin D Effects on Bone Homeostasis and Cardiovascular System in Patients with Chronic Kidney Disease and Renal Transplant Recipients.
Cianciolo, G, Cappuccilli, M, Tondolo, F, Gasperoni, L, Zappulo, F, Barbuto, S, Iacovella, F, Conte, D, Capelli, I, La Manna, G
Nutrients. 2021;(5)
Abstract
Poor vitamin D status is common in patients with impaired renal function and represents one main component of the complex scenario of chronic kidney disease-mineral and bone disorder (CKD-MBD). Therapeutic and dietary efforts to limit the consequences of uremia-associated vitamin D deficiency are a current hot topic for researchers and clinicians in the nephrology area. Evidence indicates that the low levels of vitamin D in patients with CKD stage above 4 (GFR < 15 mL/min) have a multifactorial origin, mainly related to uremic malnutrition, namely impaired gastrointestinal absorption, dietary restrictions (low-protein and low-phosphate diets), and proteinuria. This condition is further worsened by the compromised response of CKD patients to high-dose cholecalciferol supplementation due to the defective activation of renal hydroxylation of vitamin D. Currently, the literature lacks large and interventional studies on the so-called non-calcemic activities of vitamin D and, above all, the modulation of renal and cardiovascular functions and immune response. Here, we review the current state of the art of the benefits of supplementation with native vitamin D in various clinical settings of nephrological interest: CKD, dialysis, and renal transplant, with a special focus on the effects on bone homeostasis and cardiovascular outcomes.
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9.
Muscle-bone axis in children with chronic kidney disease: current knowledge and future perspectives.
Karava, V, Dotis, J, Christoforidis, A, Kondou, A, Printza, N
Pediatric nephrology (Berlin, Germany). 2021;(12):3813-3827
Abstract
Bone and muscle tissue are developed hand-in-hand during childhood and adolescence and interact through mechanical loads and biochemical pathways forming the musculoskeletal system. Chronic kidney disease (CKD) is widely considered as both a bone and muscle-weakening disease, eventually leading to frailty phenotype, with detrimental effects on overall morbidity. CKD also interferes in the biomechanical communication between two tissues. Pathogenetic mechanisms including systemic inflammation, anorexia, physical inactivity, vitamin D deficiency and secondary hyperparathyroidism, metabolic acidosis, impaired growth hormone/insulin growth factor 1 axis, insulin resistance, and activation of renin-angiotensin system are incriminated for longitudinal uncoordinated loss of bone mineral content, bone strength, muscle mass, and muscle strength, leading to mechanical impairment of the functional muscle-bone unit. At the same time, CKD may also interfere in the biochemical crosstalk between the two organs, through inhibiting or stimulating the expression of certain osteokines and myokines. This review focuses on presenting current knowledge, according to in vitro, in vivo, and clinical studies, concerning the pathogenetic pathways involved in the muscle-bone axis, and suggests approaches aimed at preventing bone loss and muscle wasting in the pediatric population. Novel therapeutic targets for preserving musculoskeletal health in the context of CKD are also discussed.
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10.
Hormonal regulation of biomineralization.
Arnold, A, Dennison, E, Kovacs, CS, Mannstadt, M, Rizzoli, R, Brandi, ML, Clarke, B, Thakker, RV
Nature reviews. Endocrinology. 2021;(5):261-275
Abstract
Biomineralization is the process by which organisms produce mineralized tissues. This crucial process makes possible the rigidity and flexibility that the skeleton needs for ambulation and protection of vital organs, and the hardness that teeth require to tear and grind food. The skeleton also serves as a source of mineral in times of short supply, and the intestines absorb and the kidneys reclaim or excrete minerals as needed. This Review focuses on physiological and pathological aspects of the hormonal regulation of biomineralization. We discuss the roles of calcium and inorganic phosphate, dietary intake of minerals and the delicate balance between activators and inhibitors of mineralization. We also highlight the importance of tight regulation of serum concentrations of calcium and phosphate, and the major regulators of biomineralization: parathyroid hormone (PTH), the vitamin D system, vitamin K, fibroblast growth factor 23 (FGF23) and phosphatase enzymes. Finally, we summarize how developmental stresses in the fetus and neonate, and in the mother during pregnancy and lactation, invoke alternative hormonal regulatory pathways to control mineral delivery, skeletal metabolism and biomineralization.