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      Calcium intake and risk of fracture: systematic review

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          Abstract

          Objective To examine the evidence underpinning recommendations to increase calcium intake through dietary sources or calcium supplements to prevent fractures.

          Design Systematic review of randomised controlled trials and observational studies of calcium intake with fracture as an endpoint. Results from trials were pooled with random effects meta-analyses.

          Data sources Ovid Medline, Embase, PubMed, and references from relevant systematic reviews. Initial searches undertaken in July 2013 and updated in September 2014.

          Eligibility criteria for selecting studies Randomised controlled trials or cohort studies of dietary calcium, milk or dairy intake, or calcium supplements (with or without vitamin D) with fracture as an outcome and participants aged >50.

          Results There were only two eligible randomised controlled trials of dietary sources of calcium (n=262), but 50 reports from 44 cohort studies of relations between dietary calcium (n=37), milk (n=14), or dairy intake (n=8) and fracture outcomes. For dietary calcium, most studies reported no association between calcium intake and fracture (14/22 for total, 17/21 for hip, 7/8 for vertebral, and 5/7 for forearm fracture). For milk (25/28) and dairy intake (11/13), most studies also reported no associations. In 26 randomised controlled trials, calcium supplements reduced the risk of total fracture (20 studies, n=58 573; relative risk 0.89, 95% confidence interval 0.81 to 0.96) and vertebral fracture (12 studies, n=48 967. 0.86, 0.74 to 1.00) but not hip (13 studies, n=56 648; 0.95, 0.76 to 1.18) or forearm fracture (eight studies, n=51 775; 0.96, 0.85 to 1.09). Funnel plot inspection and Egger’s regression suggested bias toward calcium supplements in the published data. In randomised controlled trials at lowest risk of bias (four studies, n=44 505), there was no effect on risk of fracture at any site. Results were similar for trials of calcium monotherapy and co-administered calcium and vitamin D. Only one trial in frail elderly women in residential care with low dietary calcium intake and vitamin D concentrations showed significant reductions in risk of fracture.

          Conclusions Dietary calcium intake is not associated with risk of fracture, and there is no clinical trial evidence that increasing calcium intake from dietary sources prevents fractures. Evidence that calcium supplements prevent fractures is weak and inconsistent.

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          Most cited references71

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          Vitamin D3 and calcium to prevent hip fractures in the elderly women.

          Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.
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            Estimation of total usual calcium and vitamin D intakes in the United States.

            Our objective in this study was to estimate calcium intakes from food, water, dietary supplements, and antacids for U.S. citizens aged >or=1 y using NHANES 2003-2006 data and the Dietary Reference Intake panel age groupings. Similar estimates were calculated for vitamin D intake from food and dietary supplements using NHANES 2005-2006. Diet was assessed with 2 24-h recalls; dietary supplement and antacid use were determined by questionnaire. The National Cancer Institute method was used to estimate usual nutrient intake from dietary sources. The mean daily nutrient intake from supplemental sources was added to the adjusted dietary intake estimates to produce total usual nutrient intakes for calcium and vitamin D. A total of 53% of the U.S. population reported using any dietary supplement (2003-2006), 43% used calcium (2003-2006), and 37% used vitamin D (2005-2006). For users, dietary supplements provided the adequate intake (AI) recommendation for calcium intake for approximately 12% of those >or=71 y. Males and females aged 1-3 y had the highest prevalence of meeting the AI from dietary and total calcium intakes. For total vitamin D intake, males and females >or=71, and females 14-18 y had the lowest prevalence of meeting the AI. Dietary supplement use is associated with higher prevalence of groups meeting the AI for calcium and vitamin D. Monitoring usual total nutrient intake is necessary to adequately characterize and evaluate the population's nutritional status and adherence to recommendations for nutrient intake.
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              Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials.

              The purpose of this study was to extend the metaanalysis of Bischoff-Ferrari et al., which found that 700-800 IU/d vitamin D reduced hip fracture risk in elderly individuals by 25%, by defining the need for additional calcium supplementation in individuals receiving vitamin D for the prevention of hip fractures. MEDLINE and EMBASE.com (search terms: "vitamin D" and "hip fracture"), bibliographies of articles retrieved, and the authors' reference files were used as data sources. Selected studies were randomized controlled trials (RCTs) of oral vitamin D with or without calcium supplementation vs. placebo/no treatment in postmenopausal women and/or older men (>or=50 yr) specifically reporting a risk of hip fracture. Independent extraction was performed by two authors using predefined criteria, including study quality indicators. All pooled analyses are based on random-effects models. Based on four RCTs (9083 patients), the pooled relative risk (RR) of hip fracture for vitamin D alone was 1.10 [95% confidence intervals (CI) 0.89, 1.36]. No between-trial heterogeneity was observed. For the six RCTs (45,509 patients) of vitamin D with calcium supplementation, the pooled RR for hip fracture was 0.82 (95% CI 0.71, 0.94). There was no heterogeneity between trials. In an adjusted indirect comparison of the summary RRs from the two metaanalyses, the RR for hip fracture for vitamin D with calcium vs. vitamin D alone was 0.75 (95% CI 0.58, 0.96). Our analyses, designed to extend the findings of Bischoff-Ferrari et al., suggest that oral vitamin D appears to reduce the risk of hip fractures only when calcium supplementation is added.
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                Author and article information

                Contributors
                Role: associate professor
                Role: health economist
                Role: medical student
                Role: radiologist
                Role: biostatistician
                Role: associate professor of medicine
                Role: professor of medicine
                Journal
                BMJ
                BMJ
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2015
                29 September 2015
                : 351
                : h4580
                Affiliations
                [1 ]Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
                [2 ]Department of Public Health, University of Otago, PO Box 7343, Wellington 6242, New Zealand
                [3 ]Department of Radiology, Starship Hospital, Private Bag 92024, Auckland 1142, New Zealand
                Author notes
                Correspondence to: M Bolland m.bolland@ 123456auckland.ac.nz
                Article
                bolm026208
                10.1136/bmj.h4580
                4784799
                26420387
                bf296661-b378-44db-a857-d8df18e47aed
                © Bolland et al 2015

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 18 August 2015
                Categories
                Research

                Medicine
                Medicine

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