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      Vitamin C intake in relation to bone mineral density and risk of hip fracture and osteoporosis: a systematic review and meta-analysis of observational studies

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          Abstract

          We aimed to systematically review available data on the association between vitamin C intake and bone mineral density (BMD), as well as risk of fractures and osteoporosis, and to summarise this information through a meta-analysis. Previous studies on vitamin C intake in relation to BMD and risk of fracture and osteoporosis were selected through searching PubMed, Scopus, ISI Web of Science and Google Scholar databases before February 2017, using MeSH and text words. To pool data, either a fixed-effects model or a random-effects model was used, and for assessing heterogeneity, Cochran’s Q and I 2 tests were used. Subgroup analysis was applied to define possible sources of heterogeneity. Greater dietary vitamin C intake was positively associated with BMD at femoral neck (pooled r 0·18; 0·06, 0·30) and lumbar spine (pooled r 0·14; 95 % CI 0·06, 0·22); however, significant between-study heterogeneity was found at femoral neck: I 2=87·6 %, P heterogeneity<0·001. In addition, we found a non-significant association between dietary vitamin C intake and the risk of hip fracture (overall relative risk=0·74; 95 % CI 0·51, 1·08). Significant between-study heterogeneity was found ( I 2=79·1 %, P heterogeneity<0·001), and subgroup analysis indicated that study design, sex and age were the main sources of heterogeneity. Greater dietary vitamin C intake was associated with a 33 % lower risk of osteoporosis (overall relative risk=0·67; 95 % CI 0·47, 0·94). Greater dietary vitamin C intake was associated with a lower risk of hip fracture and osteoporosis, as well as higher BMD, at femoral neck and lumbar spine.

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          Most cited references54

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          Pathogenesis of osteoporosis: concepts, conflicts, and prospects.

          Osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. This review examines the fundamental pathogenetic mechanisms underlying this disorder, which include: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) failure to replace lost bone due to defects in bone formation. Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute. There are multiple mechanisms underlying the regulation of bone remodeling, and these involve not only the osteoblastic and osteoclastic cell lineages but also other marrow cells, in addition to the interaction of systemic hormones, local cytokines, growth factors, and transcription factors. Polymorphisms of a large number of genes have been associated with differences in bone mass and fragility. It is now possible to diagnose osteoporosis, assess fracture risk, and reduce that risk with antiresorptive or other available therapies. However, new and more effective approaches are likely to emerge from a better understanding of the regulators of bone cell function.
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            Association between alcohol consumption and both osteoporotic fracture and bone density.

            Alcoholism is a risk factor for osteoporotic fractures and low bone density, but the effects of moderate alcohol consumption on bone are unknown. We performed a systematic review and meta-analysis to assess the associations between alcohol consumption and osteoporotic fractures, bone density and bone density loss over time, bone response to estrogen replacement, and bone remodeling. MEDLINE, Current Contents, PsychINFO, and Cochrane Libraries were searched for studies published before May 14, 2007. We assessed quality using the internal validity criteria of the US Preventive Services Task Force. We pooled effect sizes for 2 specific outcomes (hip fracture and bone density) and synthesized data qualitatively for 4 outcomes (non-hip fracture, bone density loss over time, bone response to estrogen replacement, and bone remodeling). Compared with abstainers, persons consuming from more than 0.5 to 1.0 drinks per day had lower hip fracture risk (relative risk=0.80 [95% confidence interval, 0.71-0.91]), and persons consuming more than 2 drinks per day had higher risk (relative risk=1.39 [95% confidence interval, 1.08-1.79]). A linear relationship existed between femoral neck bone density and alcohol consumption. Because studies often combined moderate and heavier drinkers in a single category, we could not assess relative associations between alcohol consumption and bone density in moderate compared with heavy drinkers. Compared with abstainers and heavier drinkers, persons who consume 0.5 to 1.0 drink per day have a lower risk of hip fracture. Although available evidence suggests a favorable effect of alcohol consumption on bone density, a precise range of beneficial alcohol consumption cannot be determined.
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              The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments.

              Vitamin C is an important antioxidant and cofactor that is involved in the regulation of development, function, and maintenance of several cell types in the body. Deficiencies in vitamin C can lead to conditions such as scurvy, which, among other ailments, causes gingivia, bone pain, and impaired wound healing. This review examines the functional importance of vitamin C as it relates to the development and maintenance of bone tissues. Analysis of several epidemiological studies and genetic mouse models regarding the effect of vitamin C shows a positive effect on bone health. Overall, vitamin C exerts a positive effect on trabecular bone formation by influencing expression of bone matrix genes in osteoblasts. Recent studies on the molecular pathway for vitamin C actions that include direct effects of vitamin C on transcriptional regulation of target genes by influencing the activity of transcription factors and by epigenetic modification of key genes involved in skeletal development and maintenance are discussed. With an understanding of mechanisms involved in the uptake and metabolism of vitamin C and knowledge of precise molecular pathways for vitamin C actions in bone cells, it is possible that novel therapeutic strategies can be developed or existing therapies can be modified for the treatment of osteoporotic fractures.
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                Author and article information

                Journal
                British Journal of Nutrition
                Br J Nutr
                Cambridge University Press (CUP)
                0007-1145
                1475-2662
                April 28 2018
                April 12 2018
                April 28 2018
                : 119
                : 8
                : 847-858
                Article
                10.1017/S0007114518000430
                29644950
                d0a97763-9159-4524-9edb-20ecceb0c1c5
                © 2018

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