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Interactions between Clinically Used Bisphosphonates and Bone Mineral: from Coordination Chemistry to Biomedical Applications and Beyond.
Gałęzowska, J
ChemMedChem. 2018;(4):289-302
Abstract
Bisphosphonates (BPs) are well-established, widely used first-choice drugs for bone-related diseases and are one of the few classes of molecules for selective bone targeting. Their binding to calcium cations within hydroxyapatite (HA) is a key physicochemical event that takes place on the bone surface. It is the starting point for a cascade of biochemical reactions and cellular effects that lead to the pharmacological activity of BPs. The phenomenon has been known for years, yet its physicochemical nature is still not fully understood. In particular, the adsorption/release processes and structure-function relationships of BPs remain to be clarified. These are elementary, yet crucial factors, which should influence the design and development of new delivery tools or drugs with improved characteristics. This review summarizes the current understanding of the chemical interactions between clinically used BPs and bone mineral, starting from basic Ca2+ coordination chemistry through to interactions with hydroxyapatite, nanocrystalline apatites, and natural bone mineral.
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Compact DD generator-based in vivo neutron activation analysis (IVNAA) system to determine sodium concentrations in human bone.
Coyne, MD, Neumann, C, Zhang, X, Byrne, P, Liu, Y, Weaver, CM, Nie, LH
Physiological measurement. 2018;(5):055004
Abstract
OBJECTIVE This study presents the development of a noninvasive method for monitoring Na in human bone. Many diseases, such as hypertension and osteoporosis, are closely associated with sodium (Na) retention in the human body. Na retention is generally evaluated by calculating the difference between dietary intake and excretion. There is currently no method to directly quantify Na retained in the body. Bone is a storage for many elements, including Na, which renders bone Na an ideal biomarker to study Na metabolism and retention. APPROACH A customized compact deuterium-deuterium (DD) neutron generator was used to produce neutrons for in vivo neutron activation analysis (IVNAA), with a moderator/reflector/shielding assembly optimized for human hand irradiation in order to maximize the thermal neutron flux inside the irradiation cave and to limit radiation exposure to the hand and the whole body. MAIN RESULTS The experimental results show that the system is able to detect sodium levels in the bone as low as 16 µg Na g-1 dry bone with an effective dose to the body of about 27 µSv. The simulation results agree with the numbers estimated from the experiment. SIGNIFICANCE This is expected to be a feasible method for measuring the change of Na in bone. The low detection limit indicates this will be a useful system to study the association between Na retention and related diseases.
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Pulsed electromagnetic fields modulate bone metabolism via RANKL/OPG and Wnt/β-catenin pathways in women with postmenopausal osteoporosis: A pilot study.
Catalano, A, Loddo, S, Bellone, F, Pecora, C, Lasco, A, Morabito, N
Bone. 2018;:42-46
Abstract
Pulsed electromagnetic fields (PEMFs) have been proven to enhance in vitro and in vivo osteogenesis with unknown mechanism. Aim of our study was to explore whether RANKL/OPG and Wnt/β-Catenin pathways could be involved in bone response to PEMFs in a setting of postmenopausal osteoporotic women. Forty-three women (mean age 62.8 ± 4.5 yr.) were randomized into two groups. The PEMFs group received PEMFs treatment (50 min treatment session/day, 6 treatment sessions/week, for a total of 25 times), by wearing a specific gilet applied to the trunk and connected to the electromagnetic device (Biosalus, by HSD Srl, Serravalle RSM), while women assigned to control group received sham PEMFs with the same device. BSAP as bone formation and CTX as bone resorption markers, RANKL, OPG, β-Catenin, DKK-1 and sclerostin were obtained at baseline, after 30 and 60 days. In PEMFs group, BSAP levels significantly increased after 30 and 60 days while CTX concentrations decreased at day 60. RANKL levels significantly decreased after 60 days. OPG was not significantly changed, but the RANKL/OPG ratio significantly decreased at day 30. DKK-1 levels decreased, while β-catenin concentrations increased after 30 and 60 days (P < 0.05). No significant changes of calcium, phosphorus, creatinine and sclerostin were detected. In the PEMFs group, at day 30, Δsclerostin was associated with ΔRANKL/OPG ratio (r = -0.5, P = 0.03) and ΔDKK-1 was associated with Δβ-Catenin (r = -0.47, P = 0.02). In women with postmenopausal osteoporosis, our data provide evidence of a PEMFs modulation of RANKL/OPG and Wnt/β-Catenin signaling pathways able to explain the metabolic effects of PEMFs on bone.
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Obesity, Bariatric Surgery, and Vitamin D.
Borges, JLC, Miranda, ISM, Sarquis, MMS, Borba, V, Maeda, SS, Lazaretti-Castro, M, Blinkey, N
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2018;(2):157-162
Abstract
The high prevalence of obesity is a worldwide problem associated with multiple comorbidities, including cardiovascular diseases. Vitamin D deficiency with secondary hyperparathyroidism is common in obese individuals and can be aggravated after bariatric surgery. Moreover, there is no consensus on the optimal supplementation dose of vitamin D in postbariatric surgical patients. We present new data on the variability of 25(OH)D response to supplementation in postmenopausal obese women. It is important to recognize and treat vitamin D deficiency before bariatric surgery to avoid postoperative complications, such as metabolic bone disease with associated high fracture risk. The objective of this article is to discuss the bone metabolism consequences of vitamin D deficiency after bariatric surgery.
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5.
The Effects of Homocysteine on the Skeleton.
Saito, M, Marumo, K
Current osteoporosis reports. 2018;(5):554-560
Abstract
PURPOSE OF REVIEW Homocystinuria is a congenital metabolic disorder in which cystathionine β-synthase deficiency results in a prominent increase in homocysteine (serum levels > 100 μM), causing mental retardation, atherosclerotic cerebral infarction, and osteoporosis accompanied by fragility fractures. Encountering a case with excessive homocysteinemia such as that seen in hereditary homocystinuria is unlikely during usual medical examinations. However, in individuals who have vitamin B or folate deficiency, serum homocysteine concentrations are known to increase. These individuals may also have a polymorphism in methylenetetrahydrofolate reductase, MTHFR (C677T: TT type), which regulates homocysteine metabolism. These changes in homocysteine levels may elicit symptoms resembling those of homocystinuria (e.g., Alzheimer's disease, atherosclerosis, osteoporosis). RECENT FINDINGS High serum homocysteine has been shown to have detrimental effects on neural cells, vascular endothelial cells, osteoblasts, and osteoclasts. Homocysteine is also known to increase oxidative stress, disrupt cross-linking of collagen molecules, and increase levels of advanced glycation end products, which results in reduced bone strength through a mechanism that goes beyond low bone density and increased bone resorption. Therefore, high serum homocysteine may be regarded as a factor that can reduce both bone mass and impair bone quality. In this review, we outline the epidemiology and pathophysiology of osteoporosis associated with hyperhomocysteinemia.
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The effect of a high-impact jumping intervention on bone mass, bone stiffness and fitness parameters in adolescent athletes.
Vlachopoulos, D, Barker, AR, Ubago-Guisado, E, Williams, CA, Gracia-Marco, L
Archives of osteoporosis. 2018;(1):128
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Abstract
UNLABELLED This study demonstrates that a 9-month jumping intervention can improve bone mass gains and physical fitness performance in adolescent males participating in non-osteogenic sports, such as swimming and cycling. PURPOSE To examine the effect of a jumping intervention on bone mass, bone stiffness and fitness parameters in adolescents involved in different sports. METHODS Ninety-three adolescent male swimmers (SWI), footballers (FOO) and cyclists (CYC) were randomised to intervention (INT) and sport (INT-SWI = 19, INT-FOO = 15, INT-CYC = 14) or sport only (CON-SWI = 18, CON-FOO = 15, CON-CYC = 12) groups. The 9-month jumping intervention consisted of 3 levels (12 weeks each) of 20 repetitions per set of counter movement jumps (CMJ) using adjustable weight vests (level 1 = 20 CMJ jumps/set, 0 kg, 3 sets/day, 3 times/week; level 2 = 20 CMJ jumps/set, 2 kg, 4 sets/day, 3 times/week; level 3 = 20 CMJ jumps/set, 5 kg, 4 sets/day, 4 times/week). Total body bone mineral content (BMC) at total body less head (TBLH) was measured using dual-energy X-ray absorptiometry and bone stiffness using quantitative ultrasound. Fitness was assessed using the 20-m shuttle run (20mSRT), CMJ and standing long jump (SLJ) tests. RESULTS INT-SWI had significantly higher increase in BMC legs and bone stiffness compared to CON-SWI (4.2-12.7%). INT-CYC had significantly higher increase in BMC at TBLH and legs and bone stiffness compared to CON-CYC (5.0-12.3%). There were no significant differences between INT-FOO and CON-FOO in any bone outcomes (0.9-3.9%). The increase in CMJ performance was significantly higher in INT-SWI (3.1 cm) and INT-CYC (3.2 cm) compared to CON-SWI and CON-CYC groups, respectively. CONCLUSIONS A 9-month jumping intervention can improve bone mass, bone stiffness and muscular fitness in adolescent males participating in non-osteogenic sports, such as swimming and cycling. CLINICAL TRIAL REGISTRATION ISRCTN17982776.
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Associations between bone-alkaline phosphatase and bone mineral density in adults with and without diabetes.
Chen, H, Li, J, Wang, Q
Medicine. 2018;(17):e0432
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Abstract
Insufficient evidence is available to reliably compare the roles of bone alkaline phosphatase (BAP) and bone mineral density (BMD) in diabetes. This study aimed to compare associations between BAP and BMD in adults with and without diabetes to elucidate fracture risk in diabetes.Data were extracted from the National Health and Nutrition Examination Survey (NHANES), 2001-2004, including 4197 adults aged 20 to 49 years, 143 with diabetes (DM group), and 4054 without (non-DM group). Main outcome measure was BMD and regression analyses were performed to identify serum BAP and other covariates associated with total BMD.BMD decreased significantly in DM patients when BAP was increased. In the non-DM group, all BMD results were significantly decreased when BAP was increased. Factors associated with total BMD varied with DM status. Lifestyle measures such as smoking and physical activity were also associated with BMD in the non-DM group.BAP and BMD are inversely associated in DM and non-DM patients. BAP is significantly associated with BMD after controlling for other variables, suggesting that BAP may interact with other factors altering bone metabolism in DM patients.
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8.
Bones and muscular dystrophies: what do we know?
Wood, CL, Straub, V
Current opinion in neurology. 2018;(5):583-591
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Abstract
PURPOSE OF REVIEW Muscle and bone are intrinsically linked, and therefore, it is not surprising that many muscular dystrophies are associated with impaired bone health and increased risk of osteoporosis. Osteoporotic fracture is an important and preventable cause of morbidity and mortality. This article will firstly review the general causes of impaired bone health in muscular dystrophies and then focus on the evidence available for the diagnosis and treatment of osteoporosis in specific conditions. RECENT FINDINGS With the exception of DMD, there is a paucity of data regarding bone health in muscular dystrophies. However, it appears that in common with all types of muscular dystrophies that cause a significant level of muscle weakness and disability there is an increased risk of falls, fractures and decreased vitamin D levels. A better understanding of the extent of the impaired bone health and underlying causes could help to identify potential new therapeutic agents and aid clinical care. SUMMARY It would be prudent for clinicians to assess fracture risk in their muscular dystrophy patients and if appropriate, arrange surveillance and recommend vitamin D supplementation. Additionally, fracture should be considered in any patient presenting with new-onset bone pain.
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Effects of Gymnastics Activities on Bone Accrual during Growth: A Systematic Review.
Jürimäe, J, Gruodyte-Raciene, R, Baxter-Jones, ADG
Journal of sports science & medicine. 2018;(2):245-258
Abstract
The amount of bone gained during childhood and adolescence impacts greatly on lifetime skeletal health. The purpose of this review is to summarize current evidence of the effects of gymnastics activities on bone mineral accrual during growth and to describe possible factors that influence bone mineral gains. The PubMed and SportDiscus databases were searched, and a total of 24 articles met the selection criteria and were included in this review. Artistic and rhythmic gymnasts presented higher bone mineral density and content values compared to untrained controls, despite possible negative effects associated with hormonal levels, dietary restrictions and body fat. The results suggest that gymnasts had similar bone turnover values compared to untrained controls. High-intensity mechanical loading of gymnastics activity appears to increase bone development and counterbalance negative effects, such as later pubertal development, lower body fat mass and lower hormone levels. In conclusion, gymnasts present higher bone mineral values in comparison with untrained controls. The osteogenic effect of gymnastics athletic activity has a positive influence on bone mineral accrual and overcomes the possible negative influence of high athletic activity that may cause negative energy balance and low body fat mass which are associated with lower bone accrual.
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Calcium Intake in Bone Health: A Focus on Calcium-Rich Mineral Waters.
Vannucci, L, Fossi, C, Quattrini, S, Guasti, L, Pampaloni, B, Gronchi, G, Giusti, F, Romagnoli, C, Cianferotti, L, Marcucci, G, et al
Nutrients. 2018;(12)
Abstract
Calcium is an essential element that plays numerous biological functions in the human body, of which one of the most important is skeleton mineralization. Bone is a mineralized connective tissue in which calcium represents the major component, conferring bone strength and structure. Proper dietary calcium intake is important for bone development and metabolism, and its requirement can vary throughout life. The mineral composition of drinking water is becoming relevant in the modulation of calcium homeostasis. In fact, calcium present in mineral drinking waters is an important quantitative source of calcium intake. This, together with its excellent bioavailability, contributes to the maintenance of the bone health. This article aims to examine studies that assessed the bioavailability of the calcium contained in calcium-rich mineral waters and their impact on bone health, including original data collected in a recent study in humans.