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1.
Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis.
Bolland, MJ, Grey, A, Avenell, A
The lancet. Diabetes & endocrinology. 2018;(11):847-858
Abstract
BACKGROUND The effects of vitamin D on fractures, falls, and bone mineral density are uncertain, particularly for high vitamin D doses. We aimed to determine the effect of vitamin D supplementation on fractures, falls, and bone density. METHODS In this systematic review, random-effects meta-analysis, and trial sequential analysis, we used findings from literature searches in previously published meta-analyses. We updated these findings by searching PubMed, Embase, and Cochrane Central on Sept 14, 2017, and Feb 26, 2018, using the search term "vitamin D" and additional keywords, without any language restrictions. We assessed randomised controlled trials of adults (>18 years) that compared vitamin D with untreated controls, placebo, or lower-dose vitamin D supplements. Trials with multiple interventions (eg, co-administered calcium and vitamin D) were eligible if the study groups differed only by use of vitamin D. We excluded trials of hydroxylated vitamin D analogues. Eligible studies included outcome data for total or hip fractures, falls, or bone mineral density measured at the lumbar spine, total hip, femoral neck, total body, or forearm. We extracted data about participant characteristics, study design, interventions, outcomes, funding sources, and conflicts of interest. The co-primary endpoints were participants with at least one fracture, at least one hip fracture, or at least one fall; we compared data for fractures and falls using relative risks with an intention-to-treat analysis using all available data. The secondary endpoints were the percentage change in bone mineral density from baseline at lumbar spine, total hip, femoral neck, total body, and forearm. FINDINGS We identified 81 randomised controlled trials (n=53 537 participants) that reported fracture (n=42), falls (n=37), or bone mineral density (n=41). In pooled analyses, vitamin D had no effect on total fracture (36 trials; n=44 790, relative risk 1·00, 95% CI 0·93-1·07), hip fracture (20 trials; n=36 655, 1·11, 0·97-1·26), or falls (37 trials; n=34 144, 0·97, 0·93-1·02). Results were similar in randomised controlled trials of high-dose versus low-dose vitamin D and in subgroup analyses of randomised controlled trials using doses greater than 800 IU per day. In pooled analyses, there were no clinically relevant between-group differences in bone mineral density at any site (range -0·16% to 0·76% over 1-5 years). For total fracture and falls, the effect estimate lay within the futility boundary for relative risks of 15%, 10%, 7·5%, and 5% (total fracture only), suggesting that vitamin D supplementation does not reduce fractures or falls by these amounts. For hip fracture, at a 15% relative risk, the effect estimate lay between the futility boundary and the inferior boundary, meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount, but uncertainty remains as to whether it might increase hip fractures. The effect estimate lay within the futility boundary at thresholds of 0·5% for total hip, forearm, and total body bone mineral density, and 1·0% for lumbar spine and femoral neck, providing reliable evidence that vitamin D does not alter these outcomes by these amounts. INTERPRETATION Our findings suggest that vitamin D supplementation does not prevent fractures or falls, or have clinically meaningful effects on bone mineral density. There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health. This conclusion should be reflected in clinical guidelines. FUNDING Health Research Council of New Zealand.
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2.
Prevalence of reduced bone mineral density in adults with coeliac disease - are we missing opportunities for detection in patients below 50 years of age?
Pritchard, L, Wilson, S, Griffin, J, Pearce, G, Murray, IA, Lewis, S
Scandinavian journal of gastroenterology. 2018;(12):1433-1436
Abstract
OBJECTIVE There are little data on the prevalence of reduced bone mineral density (BMD) in young adult patients with coeliac disease; guidelines do not support routine investigation of these patients. We assessed the prevalence of reduced BMD in our patients by age. PATIENTS AND METHODS Prospective observational study of 260 coeliac patients having DXA one year after commencing gluten-free diet. Nonparametric tests and regression were used. RESULTS Median age was 51years, BMI 24 and 85 (32.7%) were male. Reduced BMD was associated with increasing age (p < .001), female sex (p = .005), low BMI (p < .001) and previous fracture (p < .01); 49% of all patients and all patients under 20 years old had reduced BMD. The median age of patients with BMI <20 kgm2 was 56 (27, 70) years with the majority of younger patients having normal BMI. CONCLUSIONS Low BMD is a common finding in young patients with coeliac disease, yet routine assessment of BMD is not currently supported by national guidelines. Early identification may improve motivation to comply with GFD and allow adequate calcium and vitamin D supplementation to reduce risk of fracture later in life.
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3.
Outside the Bone: What Is Happening Systemically to Influence Fracture Healing?
Kates, SL, Satpathy, J, Petrisor, BA, Konda, SR, McKee, MD, Schemitsch, EH
Journal of orthopaedic trauma. 2018;:S33-S36
Abstract
This article summarizes presentations of a symposium on bone health-related hot topics of the 2016 Basic Science Focus Forum. Taken together, these topics emphasize the critical importance of bone health in fracture management, the systemic factors that influence fracture healing, and the need to focus on issues other than simply the technical aspects of fracture repair.
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4.
Adherence to Mediterranean diet in relation to bone mineral density and risk of fracture: a systematic review and meta-analysis of observational studies.
Malmir, H, Saneei, P, Larijani, B, Esmaillzadeh, A
European journal of nutrition. 2018;(6):2147-2160
Abstract
PURPOSE We aimed to systematically review available data on the association between adherence to MD and BMD as well as risk of fractures and to summarize this information through a meta-analysis. METHODS Previous studies in the field of adherence to MD in relation to BMD and risk of fracture were selected through searching PubMed, Scopus, ISI Web of Science and Google Scholar databases prior to June, 2016 using Mesh and non-Mesh relevant keywords. RESULTS In the meta-analysis of four effect sizes, obtained from three studies, we found that adherence to MD was associated with a 21% reduced risk of hip fracture (overall RR 0.79; 95% CIs 0.72-0.87). Adherence to MD was positively associated with lumber spine's (mean difference of BMD comparing highest and lowest categories of MD score 0.12; 95% CI 0.06-0.19 g/cm2), femoral neck (0.10; 0.06-0.15 g/cm2) and total hip (0.11; 0.09-0.14 g/cm2) BMD. Meta-regression of included observational studies revealed a significant inverse linear association between Mediterranean diet score and risk of hip fracture, such that one unit increase in the score of Mediterranean diet was associated with a reduction in the risk of hip fracture (RR 0.95, 95% CI 0.92-0.98 p = 0.01). CONCLUSION Adherence to MD was associated with a reduced risk of fracture as well as with a higher mean BMD.
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5.
Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.
Kahwati, LC, Weber, RP, Pan, H, Gourlay, M, LeBlanc, E, Coker-Schwimmer, M, Viswanathan, M
JAMA. 2018;(15):1600-1612
Abstract
IMPORTANCE Osteoporotic fractures result in significant morbidity and mortality. OBJECTIVE To update the evidence for benefits and harms of vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults to inform the US Preventive Services Task Force. DATA SOURCES PubMed, EMBASE, Cochrane Library, and trial registries through March 21, 2017; references; and experts. Surveillance continued through February 28, 2018. STUDY SELECTION English-language randomized clinical trials (RCTs) or observational studies of supplementation with vitamin D, calcium, or both among adult populations; studies of populations that were institutionalized or had known vitamin D deficiency, osteoporosis, or prior fracture were excluded. DATA EXTRACTION AND SYNTHESIS Dual, independent review of titles/abstracts and full-text articles and study quality rating using predefined criteria. Random-effects meta-analysis used when at least 3 similar studies were available. MAIN OUTCOMES AND MEASURES Incident fracture, mortality, kidney stones, cardiovascular events, and cancer. RESULTS Eleven RCTs (N = 51 419) in adults 50 years and older conducted over 2 to 7 years were included. Compared with placebo, supplementation with vitamin D decreased total fracture incidence (1 RCT [n = 2686]; absolute risk difference [ARD], -2.26% [95% CI, -4.53% to 0.00%]) but had no significant association with hip fracture (3 RCTs [n = 5496]; pooled ARD, -0.01% [95% CI, -0.80% to 0.78%]). Supplementation using vitamin D with calcium had no effect on total fracture incidence (1 RCT [n = 36 282]; ARD, -0.35% [95% CI, -1.02% to 0.31%]) or hip fracture incidence (2 RCTs [n = 36 727]; ARD from the larger trial, -0.14% [95% CI, -0.34% to 0.07%]). The evidence for calcium alone was limited, with only 2 studies (n = 339 total) and very imprecise results. Supplementation with vitamin D alone or with calcium had no significant effect on all-cause mortality or incident cardiovascular disease; ARDs ranged from -1.93% to 1.79%, with CIs consistent with no significant differences. Supplementation using vitamin D with calcium was associated with an increased incidence of kidney stones (3 RCTs [n = 39 213]; pooled ARD, 0.33% [95% CI, 0.06% to 0.60%]), but supplementation with calcium alone was not associated with an increased risk (3 RCTs [n = 1259]; pooled ARD, 0.00% [95% CI, -0.87% to 0.87%]). Supplementation with vitamin D and calcium was not associated with an increase in cancer incidence (3 RCTs [n = 39 213]; pooled ARD, -1.48% [95% CI, -3.32% to 0.35%]). CONCLUSIONS AND RELEVANCE Vitamin D supplementation alone or with calcium was not associated with reduced fracture incidence among community-dwelling adults without known vitamin D deficiency, osteoporosis, or prior fracture. Vitamin D with calcium was associated with an increase in the incidence of kidney stones.
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6.
[Irisin as a new marker for the early diagnosis of low-traumatic fractures in rheumatoid arthritis.].
Lavrova, DP, Zavodovsky, BV, Akhverdyan, YR, Polyakova, YV, Sivordova, LE, Zborovskaya, IA, Yakovlev, AT
Klinicheskaia laboratornaia diagnostika. 2018;(11):702-706
Abstract
The aim of this study was to study the relationship between serum irisin level and the presence of low-traumatic bone fractures in rheumatoid arthritis (RA) patients. We examined 170 people including 110 RA patients and 60 healthy individuals as comparison group. The serum irisin level was determined with solid-phase enzyme-linked immunosorbent assay using ELISA Irisin test system (BioVendor, cat. No. RAG018R). The average level of irisin in the group of healthy individuals was 20.49 ± 4.82 μg/ml (μ±σ). The level of normal values, defined as M ± 2σ, was 10.85-30.13 μg/ml. Decreased irisin level was detected in 41 of 110 patients with RA diagnosis (37% of cases). This group of patients had higher RA activity degree (DAS28), extra-articular manifestations, disease duration from 5 to 10 years, greater class of functional joint's failure, lower level of 25 (OH) -vitamin D. There was also a reliable relationship between serum irisin level and presence of low-fracture bone fractures in the anamnesis.
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7.
Prevalence of vitamin D insufficiency and evidence for disease prevention in the older population.
Kühn, J, Trotz, P, Stangl, GI
Zeitschrift fur Gerontologie und Geriatrie. 2018;(5):567-572
Abstract
The prevalence of vitamin D insufficiency, usually assessed by the analysis of circulating 25-hydroxyvitamin D (25[OH])D), is very high in the aging German population. An important factor that reduces endogenous vitamin D synthesis in older persons is physical inactivity or care-dependency that limits the time spent outside. Additionally, it has been suggested that the age-dependent decline in the glomerular filtration rate is associated with a reduced production of bioactive calcitriol. As this phenomenon is not detectable by the assessment of 25(OH)D, it is necessary to analyze the level of parathyroid hormone as a marker of calcitriol function. Because 25(OH)D levels are highly correlated with an active and healthy life style, data from epidemiological studies are not necessarily suitable to elucidate the role of vitamin D in disease prevention. Recently published meta-analyses of randomized controlled trials (RCTs) showed moderate effects of vitamin D supplementation on fracture risk and found that vitamin D was more effective when administered in combination with calcium. The role of vitamin D in the prevention of falls and frailty remains unclear. Much evidence has demonstrated the beneficial effects of vitamin D on respiratory tract infections and asthma, which are very relevant health issues in the older population. To conclude, vitamin D, particularly combined with calcium, has moderately beneficial effects on the skeletal system and is useful for the prevention of respiratory tract infections.
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8.
Dietary Patterns, Bone Mineral Density, and Risk of Fractures: A Systematic Review and Meta-Analysis.
Denova-Gutiérrez, E, Méndez-Sánchez, L, Muñoz-Aguirre, P, Tucker, KL, Clark, P
Nutrients. 2018;(12)
Abstract
The aim of this systematic review was to assess the evidence on the relation between dietary patterns, bone mineral density (BMD), and risk of fracture in different age groups. Medline and Embase were searched for articles that identified dietary patterns and related these to BMD or risk of fracture through May 2018. Multivariable adjusted odds ratios (ORs) and 95% confidence intervals (95%CI) comparing the lowest and highest categories of dietary pattern were combined by using a random effects meta-analysis. In total, 31 studies were selected for review, including 18 cohorts, 1 case-control, and 12 cross-sectional studies, in the meta-analysis of Prudent/healthy and Western/unhealthy dietary pattern, BMD, and risk of fracture. There was evidence of a lower risk of fracture when intakes in the highest categories were compared with the lowest categories of Prudent/healthy dietary pattern (OR = 0.81; 95%CI: 0.69, 0.95; p = 0.01). In contrast, when intakes in the highest categories were compared with the lowest categories of Western/unhealthy dietary pattern, a greater risk of fracture (OR = 1.10; 95%CI: 1.02, 1.19; p = 0.01) was observed among men. The present systematic review and meta-analysis provides evidence of an inverse association between a Prudent/healthy dietary pattern and risk of low BMD and a positive relation between Western/unhealthy dietary pattern and risk of low BMD.
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9.
Adherence to a Mediterranean-style diet and incident fractures: pooled analysis of observational evidence.
Kunutsor, SK, Laukkanen, JA, Whitehouse, MR, Blom, AW
European journal of nutrition. 2018;(4):1687-1700
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Abstract
PURPOSE The Mediterranean diet is associated with decreased morbidity and mortality from various chronic diseases. Adherence to a Mediterranean-style diet has been suggested to have protective effects on bone health and decreases the incidence of bone fractures, but the evidence is not clear. We conducted a systematic review and meta-analysis of available observational studies to quantify the association between adherence to a Mediterranean-style diet, as assessed by the Mediterranean Diet Score (MDS), and the risk of fractures in the general population. METHODS Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, and reference lists of relevant studies to October 2016. Relative risks (RRS) with 95% confidence intervals (CIs) were aggregated using random-effects models. RESULTS Five observational studies with data on 353,076 non-overlapping participants and 33,576 total fractures (including 6,881 hip fractures) were included. The pooled fully adjusted RR (95% CI) for hip fractures per 2-point increment in adherence to the MDS was 0.82 (0.71-0.96). Adherence to the MDS was not associated with the risk of any or total fractures based on pooled analysis of only two studies. CONCLUSION Limited observational evidence supports a beneficial effect of adherence to a Mediterranean-style diet on the incidence of hip fractures. Well-designed intervention studies are needed to elucidate the relationship between adherence to a Mediterranean-style diet and the risk of adverse bone health outcomes such as fractures.
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10.
[Adverse effects of long-term proton-pump inhibitor therapy on adults].
Igaz, I, Simonyi, G, Balogh, S, Szathmári, M
Orvosi hetilap. 2018;(19):735-740
Abstract
In the last few decades, proton-pump inhibitors have become the mainstay of the treatment of acid-related disorders. Despite their efficacy, these drugs are not without risks. Recently several articles have been published on their long-term adverse effects. Among these adverse effects, the higher risk of bone fractures, the vitamin B12 and magnesium deficiencies and the higher risk of Clostridium difficile infection may be relevant. As these drugs are prescribed more and more frequently all over the world, the knowledge of the long-term adverse effects is very important not only for the specialists but for the general practitioners as well. In this review, the authors discuss the recent findings in this field, emphasising that the long-term use of these drugs must be based on an adequate and strong indication. Orv Hetil. 2018; 159(19): 735-740.