Diligent engagement
Zero clients were working in form the analysis question and/or benefit procedures, nor was indeed they mixed up in design and you will utilization of new study.
Investigation possibilities
Incorporated training were randomised regulated trials inside members aged >50 in the baseline with BMD measured because of the twin times x-ray absorptiometry (DXA) or forerunner technology such photon absorptiometry. I incorporated degree you to definitely reported bone nutrient content (BMC) while the BMD try acquired from the dividing BMC from the bones urban area and in addition to a few try extremely coordinated. Training where really people during the baseline got a primary general pathology apart from osteoporosis, such as kidney failure otherwise most cancers, was in fact omitted. We incorporated degree of calcium supplements combined with almost every other treatment provided additional medication received so you can both of your arms (such calcium plus nutritional K in place of placebo as well as supplement K), and studies out of co-applied calcium and you may supplement D supplements (CaD). Randomised controlled samples out of hydroxyapatite given that a nutritional way to obtain calcium supplements was basically provided since it is created from limbs and contains almost every other vitamins, hormones, necessary protein, and you will proteins also calcium. That writer (WL or MB) processed headings and you may abstracts, and two experts (WL, MB, otherwise VT) by themselves processed a complete text away from possibly associated knowledge. The latest flow of content was shown into the profile A great inside the appendix dos.
Investigation extraction and you may synthesis
I removed advice regarding for each study on participants’ features, investigation structure, financing source and you can disputes interesting, and you will BMD from the lumbar back, femoral neck, full hip, forearm, and full human body. BMD can be mentioned within several websites in the forearm, whilst the 33% (1/3) distance is actually most commonly utilized. For every single data, we made use of the stated analysis on the forearm, despite webpages. If the several website are reported, i utilized the data towards website nearest on 33% radius. A single creator (VT) removed investigation, that have been featured by the the second blogger (MB). Chance of prejudice is actually analyzed because necessary throughout the Cochrane Handbook.11 People discrepancies was basically solved due to discussion.
The primary endpoints were the percentage changes in BMD from baseline at the five BMD sites. We categorised the studies into three groups by duration: one year was duration <18 months; two years was duration ?18 months and ?2.5 years; and others were studies lasting more than two and a half years. For studies that presented absolute data rather than percentage change from baseline, we calculated the mean percentage change from the raw data and the standard deviation of the percentage change using the approach described in the Cochrane Handbook.11 When data were presented only in figures, we used digital callipers to extract data. In four studies that reported mean data but not measures of spread,12 13 14 15 we imputed the standard deviation for the percentage change in BMD for each site from the average site and duration specific standard deviations of all other studies included in our review. We prespecified subgroup analyses based on the following variables: dietary calcium intake v calcium supplements; risk of bias; calcium monotherapy v CaD; baseline age (<65); sex; community v institutionalised participants; baseline dietary calcium intake <800 mg/day; baseline 25-hydroxyvitamin D <50 nmol/L; calcium dose (?500 v >500 mg/day and <1000 v ?1000 mg/day); and vitamin D dose <800 IU/day.
Analytics
We pooled the data using random effects meta-analyses and assessed for heterogeneity between studies using 
the I 2 statistic (I 2 >50% was considered significant heterogeneity). Funnel plots and Egger’s regression model were used to assess for the likelihood of systematic bias. We included randomised controlled trials of calcium with or without vitamin D in the primary analyses. Randomised controlled trials in which supplemental vitamin D was provided to both treatment groups, so that the groups differed only in treatment by calcium, were included in calcium monotherapy subgroup analyses, while those comparing co-administered CaD with placebo or controls were included in the CaD subgroup analyses. We included all available data from trials with factorial designs or multiple arms. Thus, for factorial randomised controlled trials we included all study arms involving a comparison of calcium versus no calcium in the primary analyses and the calcium monotherapy subgroup analysis, but only arms comparing CaD with controls in the CaD subgroup analysis. For multi-arm randomised controlled trials, we pooled data from the separate treatment arms for the primary analyses, but each treatment arm was used only once. We undertook analyses of prespecified subgroups using a random effects model when there were 10 or more studies in the analysis and three or more studies in each subgroup and performed a test for interaction between subgroups. All tests were two tailed, and P<0.05 was considered significant. All analyses were performed with Comprehensive Meta-Analysis (version 2, Biostat, Englewood, NJ).
