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1.
Bone-Specific Drug Delivery for Osteoporosis and Rare Skeletal Disorders.
Sawamoto, K, Álvarez, JV, Herreño, AM, Otero-Espinar, FJ, Couce, ML, Alméciga-Díaz, CJ, Tomatsu, S
Current osteoporosis reports. 2020;(5):515-525
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Abstract
PURPOSE OF REVIEW The skeletal system provides an important role to support body structure and protect organs. The complexity of its architecture and components makes it challenging to deliver the right amount of the drug into bone regions, particularly avascular cartilage lesions. In this review, we describe the recent advance of bone-targeting methods using bisphosphonates, polymeric oligopeptides, and nanoparticles on osteoporosis and rare skeletal diseases. RECENT FINDINGS Hydroxyapatite (HA), a calcium phosphate with the formula Ca10(PO4)6(OH)2, is a primary matrix of bone mineral that includes a high concentration of positively charged calcium ion and is found only in the bone. This unique feature makes HA a general targeting moiety to the entire skeletal system. We have applied bone-targeting strategy using acidic amino acid oligopeptides into lysosomal enzymes, demonstrating the effects of bone-targeting enzyme replacement therapy and gene therapy on bone and cartilage lesions in inherited skeletal disorders. Virus or no-virus gene therapy using techniques of engineered capsid or nanomedicine has been studied preclinically for skeletal diseases. Efficient drug delivery into bone lesions remains an unmet challenge in clinical practice. Bone-targeting therapies based on gene transfer can be potential as new candidates for skeletal diseases.
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Dietary Intake of Vitamin D from Dairy Products Reduces the Risk of Osteoporosis.
Polzonetti, V, Pucciarelli, S, Vincenzetti, S, Polidori, P
Nutrients. 2020;(6)
Abstract
Vitamin D and calcium are important dietary compounds that affect bone mass, even if other minerals (potassium, zinc, etc.) and vitamins (A, C and K) are also involved. Vitamin D and certain minerals, in fact, play an important role in calcium homeostasis and calcium absorption. Hip fracture incidence is higher in Europe and the United States, where calcium is frequently included in the human diet; while the occurrence of these fractures is lower in developing countries, where diets are often poor in calcium. This condition is named the "calcium paradox", and may be partially explained by phosphate toxicity, which can negatively affect mineral metabolism. It is important to maintain correct dietary calcium-phosphate balance in order to have a healthy life, reducing the risk of osteoporotic fractures in older people. Vitamin D can also act as a hormone; vitamin D2 (ergocalciferol) is derived from the UV-B radiation of ergosterol, the natural vitamin D precursor detected in plants, fungi, and invertebrates. Vitamin D3 (cholecalciferol) is synthesized by sunlight exposure from 7-dehydrocholesterol, a precursor of cholesterol that can also act as provitamin D3. Dietary intake of vitamin D3 is essential when the skin is exposed for short periods to ultraviolet B light (UV-B), a category of invisible light rays such as UV-A and UV-C. This can be considered the usual situation in northern latitudes during the winter season, or the typical lifestyle for older people and/or for people with very white delicate skin. The actual recommended daily intake of dietary vitamin D is strictly correlated with age, ranging from 5 μg for infants, children, teenagers, and adults-including pregnant and lactating women-to 15 μg for people over 65 years.
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The Effect of Abnormal Iron Metabolism on Osteoporosis.
Che, J, Yang, J, Zhao, B, Zhang, G, Wang, L, Peng, S, Shang, P
Biological trace element research. 2020;(2):353-365
Abstract
Iron is one of the important trace elements in life activities. Abnormal iron metabolism increases the incidence of many skeletal diseases, especially for osteoporosis. Iron metabolism plays a key role in the bone homeostasis. Disturbance of iron metabolism not only promotes osteoclast differentiation and apoptosis of osteoblasts but also inhibits proliferation and differentiation of osteoblasts, which eventually destroys the balance of bone remodeling. The strength and density of bone can be weakened by the disordered iron metabolism, which increases the incidence of osteoporosis. Clinically, compounds or drugs that regulate iron metabolism are used for the treatment of osteoporosis. The goal of this review summarizes the new progress on the effect of iron overload or deficiency on osteoporosis and the mechanism of disordered iron metabolism on osteoporosis. Explaining the relationship of iron metabolism with osteoporosis may provide ideas for clinical treatment and development of new drugs.
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4.
Epigenetic Regulators of Mesenchymal Stem/Stromal Cell Lineage Determination.
Cakouros, D, Gronthos, S
Current osteoporosis reports. 2020;(5):597-605
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Abstract
PURPOSE OF REVIEW Although many signalling pathways have been discovered to be essential in mesenchymal stem/stromal (MSC) differentiation, it has become increasingly clear in recent years that epigenetic regulation of gene transcription is a vital component of lineage determination, encompassing diet, lifestyle and parental influences on bone, fat and cartilage development. RECENT FINDINGS This review discusses how specific enzymes that modify histone methylation and acetylation or DNA methylation orchestrate the differentiation programs in lineage determination of MSC and the epigenetic changes that facilitate development of bone related diseases such as osteoporosis. The review also describes how environmental factors such as mechanical loading influence the epigenetic signatures of MSC, and how the use of chemical agents or small peptides can regulate epigenetic drift in MSC populations during ageing and disease. Epigenetic regulation of MSC lineage commitment is controlled through changes in enzyme activity, which modifies DNA and histone residues leading to alterations in chromatin structure. The co-ordinated epigenetic regulation of transcriptional activation and repression act to mediate skeletal tissue homeostasis, where deregulation of this process can lead to bone loss during ageing or osteoporosis.
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Diagnosis and Monitoring of Osteoporosis with Total-Body 18F-Sodium Fluoride-PET/CT.
Zhang, V, Koa, B, Borja, AJ, Padmanhabhan, S, Bhattaru, A, Raynor, WY, Rojulpote, C, Seraj, SM, Werner, TJ, Rajapakse, C, et al
PET clinics. 2020;(4):487-496
Abstract
In recent years, 18F-Sodium Fluoride (NaF)-PET/CT has seen its role in the detection and management of osteoporosis increase. This article reviews the extent of this application in the literature, its efficacy compared with other comparable imaging tools, and how total-body PET/CT combined with global disease assessment can revolutionize measurement of total osteoporotic disease activity. NaF-PET/CT eventually can be the modality of choice for metabolic bone disorders, especially with these advances in technology and computation.
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Scientific Evidence Supporting the Beneficial Effects of Isoflavones on Human Health.
Gómez-Zorita, S, González-Arceo, M, Fernández-Quintela, A, Eseberri, I, Trepiana, J, Portillo, MP
Nutrients. 2020;(12)
Abstract
Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level.
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Impact of iron overload on bone remodeling in thalassemia.
Piriyakhuntorn, P, Tantiworawit, A, Phimphilai, M, Shinlapawittayatorn, K, Chattipakorn, SC, Chattipakorn, N
Archives of osteoporosis. 2020;(1):143
Abstract
INTRODUCTION Iron overload, a state with excessive iron storage in the body, is a common complication in thalassemia patients which leads to multiple organ dysfunctions including the bone. Iron overload-induced bone disease is one of the most common and severe complications of thalassemia including osteoporosis. Currently, osteoporosis is still frequently found in thalassemia even with widely available iron chelation therapy. STUDY SELECTION Relevant publications published before December 2019 in PubMed database were reviewed. Both pre-clinical studies and clinical trials were obtained using iron overload, thalassemia, osteoporosis, osteoblast, and osteoclast as keywords. RESULTS Increased ROS production is a hallmark of iron overload-induced impaired bone remodeling. At the cellular level, oxidative stress affects bone remodeling by both osteoblast inhibition and osteoclast activation via many signaling pathways. In thalassemia patients, it has been shown that bone resorption was increased while bone formation was concurrently reduced. CONCLUSION In this review, reports on the cellular mechanisms of iron overload-associated bone remodeling are comprehensively summarized and presented to provide current understanding this pathological condition. Moreover, current treatments and potential interventions for attenuating bone remodeling in iron overload are also summarized to pave ways for the future discoveries of novel agents that alleviate this condition.
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Celiac Disease and Its Role in the Development of Metabolic Bone Disease.
Micic, D, Rao, VL, Semrad, CE
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2020;(2):190-199
Abstract
Celiac disease (CD) is an immune-mediated enteropathy that occurs in genetically susceptible hosts with the ingestion of gluten-containing products. Ongoing gluten consumption leads to intestinal damage, characterized by villous blunting and increased intraepithelial lymphocytes, resulting in malabsorption. Pertinent to the development of bone disease, malabsorption of calcium and vitamin D leads to secondary hyperparathyroidism and metabolic bone disease among individuals with CD. In this article, we review the pathogenesis of CD and the effects of malabsorption on bone health. Imbalances in bone resorption and formation particularly in individuals with CD and persistent disease activity ultimately lead to a state of bone loss and impaired mineralization. Initiation of a gluten-free diet is critical in the management of CD-related metabolic bone disease, demonstrating improvements in bone mineral density within the first year of dietary adherence.
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Osteoporosis: evidence for vitamin D and calcium in older people.
Reid, IR
Drug and therapeutics bulletin. 2020;(8):122-125
Abstract
Topics for DTB review articles are selected by DTB's editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.
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Complicated Muscle-Bone Interactions in Children with Cerebral Palsy.
Modlesky, CM, Zhang, C
Current osteoporosis reports. 2020;(1):47-56
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Abstract
PURPOSE OF REVIEW The goal of this review is to highlight the deficits in muscle and bone in children with cerebral palsy (CP), discuss the muscle-bone relationship in the CP population, and identify muscle-based intervention strategies that may stimulate an improvement in their bone development. RECENT FINDINGS The latest research suggests that muscle and bone are both severely underdeveloped and weak in children with CP, even in ambulatory children with mild forms of the disorder. The small and low-performing muscles and limited participation in physical activity are likely the major contributors to the poor bone development in children with CP. However, the muscle-bone relationship may be complicated by other factors, such as a high degree of fat and collagen infiltration of muscle, atypical muscle activation, and muscle spasticity. Muscle-based interventions, such as resistance training, vibration, and nutritional supplementation, have the potential to improve bone development in children with CP, especially if they are initiated before puberty. Studies are needed to identify the muscle-related factors with the greatest influence on bone development in children with CP. Identifying treatment strategies that capitalize on the relationship between muscle and bone, while also improving balance, coordination, and physical activity participation, is an important step toward increasing bone strength and minimizing fractures in children with CP.