-
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
-
-
Free full text
-
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.
-
2.
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.
-
3.
An Evaluation of Bone Health Parameters in Regularly Transfused Beta-Thalassemia Major Patients.
Kothimira, VK, Kumar, A, Richhele, LR, Sood, N, Gulati, A
Journal of pediatric hematology/oncology. 2020;(6):381-385
Abstract
As beta-thalassemia major patients need regular blood transfusions due to the severe hemoglobin deficiency, the occurrence of related bone defects with simultaneous fluctuations in the biochemical and hematologic parameters is seen. The hospital-based cross-sectional observational study was done to determine and correlate the bone mineral density (BMD) with biochemical parameters and hematologic parameters in 50 regularly transfused beta-thalassemia major patients of older than 6 years of age. Descriptive statistics were analyzed with SPSS version 20.0 software. A P<0.05 was considered as statistically significant. The prevalence of suboptimal BMD at lumbar spine was 86% and at femur neck was 74%. A statistically significant correlation of BMD was found with mean pretransfusion hemoglobin values, serum calcium levels, and serum vitamin D levels (P<0.05). It was concluded that continuous monitoring of the BMD, biochemical, and hematologic parameters in regularly transfused beta-thalassemia major patients may help assess the ongoing deficiencies; helping to maintain timely and regular blood transfusions with supplementation of calcium, vitamin D to ensure good bone health.
-
4.
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.
-
5.
Epigenetic Regulators of Mesenchymal Stem/Stromal Cell Lineage Determination.
Cakouros, D, Gronthos, S
Current osteoporosis reports. 2020;(5):597-605
-
-
Free full text
-
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.
-
6.
Creatine Supplementation (3 g/d) and Bone Health in Older Women: A 2-Year, Randomized, Placebo-Controlled Trial.
Sales, LP, Pinto, AJ, Rodrigues, SF, Alvarenga, JC, Gonçalves, N, Sampaio-Barros, MM, Benatti, FB, Gualano, B, Rodrigues Pereira, RM
The journals of gerontology. Series A, Biological sciences and medical sciences. 2020;(5):931-938
Abstract
BACKGROUND Creatine supplementation could be a nonexpensive, safe, and effective dietary intervention to counteract bone loss. The aim of this study was to investigate whether long-term creatine supplementation can improve bone health in older, postmenopausal women. METHODS A double-blind, placebo-controlled, parallel-group, randomized trial was conducted between November 2011 and December 2017 in Sao Paulo, Brazil. Two hundred postmenopausal women with osteopenia were randomly allocated to receive either creatine monohydrate (3 g/d) or placebo for 2 years. At baseline and after 12 and 24 months, we assessed areal bone mineral density (aBMD; primary outcome), lean and fat mass (through dual X-ray absorptiometry), volumetric BMD and bone microarchitecture parameters, biochemical bone markers, physical function and strength, and the number of falls and fractures. Possible adverse effects were self-reported. RESULTS Lumbar spine (p < .001), femoral neck (p < .001), and total femur aBMD (p = .032) decreased across time; however, no interaction effect was observed (all p > .050). Bone markers, microarchitecture parameters, and the number of falls/fractures were not changed with creatine (all p > .050). Lean mass and appendicular skeletal muscle mass increased throughout the intervention (p < .001), with no additive effect of creatine (p = .731 and p = .397, respectively). Creatine did not affect health-related laboratory parameters. CONCLUSION Creatine supplementation more than 2 years did not improve bone health in older, postmenopausal women with osteopenia, nor did it affect lean mass or muscle function in this population. This refutes the long-lasting notion that this dietary supplement alone has osteogenic or anabolic properties in the long run. CLINICAL TRIAL REGISTRY Clinicaltrials.gov: NCT: 01472393.
-
7.
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.
-
8.
Effects of bushen qianggu method for primary osteoporosis: A protocol for systematic review and meta-analysis.
Chen, G, Guan, Y, Ye, X, Chen, G, Du, J, Liu, W, Zhao, C, Yao, N, Xu, X
Medicine. 2020;(24):e20697
-
-
Free full text
-
Abstract
BACKGROUND Primary osteoporosis (POP) is one of the most common orthopedic diseases with a high risk of fracture. Effective treatment of POP is of great significance to reduce the rate of disability and improve the quality of life. Bushen qianggu (BSQG) is a classical method of TCM in treating POP. However, there is no systematic review related to BSQG for POP. The purpose of this study is to provide a comprehensive and reliable evaluation of the clinical evidence of BSQG in the treatment of POP. METHODS AND ANALYSIS Relevant randomized controlled trial literature evaluating the effect of BSQG on patients with POP will be obtained by searching the PubMed, Embase, MEDLINE, Cochrane Library Central Register of Controlled Trials, China national knowledge infrastructure database, Wan fang database, Chongqing VIP information, and SinoMed from their inception to May 2020. Two researchers will select and evaluate qualified studies independently. The bone mineral density value and the incidence of fractures will be accepted as the primary outcomes. The meta-analyses will be performed by using the RevMan 5.3. RESULTS This study will provide a comprehensive evaluation of the efficacy and safety of BSQG method for patients with POP. CONCLUSION The conclusion of our systematic review will provide evidence to judge whether BSQG is an effective intervention for patients with POP. TRIAL REGISTRATION NUMBER 10.17605/OSF.IO/ZMX3W.
-
9.
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.
-
10.
The Case for an Estrogen-iron Axis in Health and Disease.
Hamad, M, Bajbouj, K, Taneera, J
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2020;(4):270-277
Abstract
Clinical and experimental evidence suggest that estrogen manipulates intracellular iron metabolism and that elevated levels of estrogen associate with increased systemic iron availability. This has been attributed to the ability of estrogen to suppress hepcidin synthesis, maintain ferroportin integrity and enhance iron release from iron-absorbing duodenal enterocytes and iron-storing macrophages and hepatocytes. These observations speak of a potential "estrogen-iron" axis that manipulates iron metabolism in response to hematologic (erythropoiesis) and non-hematologic (uterine growth, pregnancy, lactation) needs for iron. Such an axis could contribute to minimizing iron deficiency in premenopausal women and iron overload in postmenopausal women. It could also exacerbate iron overload and related clinical consequences including cancer, osteoporosis, cardiovascular complications and neurodegenerative symptoms, especially in postmenopausal women on hormonal replacement therapy. Understanding the role of estrogen in iron metabolism may shed some light on the pleotropic, but often paradoxical, roles of estrogen in human health and disease.