Dataset Information

Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis.

ABSTRACT:

Importance

Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness.

Objective

To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs.

Data sources

PubMed, EMBASE, Cochrane Library, and other RCT databases were searched from database inception until December 31, 2018. Searches were performed between July 2018 and December 2018.

Study selection

Observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included. Randomized clinical trials compared vitamin D or vitamin D and calcium with control.

Data extraction and synthesis

Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and assessed possible bias. Rate ratios (RRs) were estimated using fixed-effects meta-analysis. Data extraction and synthesis took place between July 2018 and June 2019.

Main outcomes and measures

Any fracture and hip fracture.

Results

In a meta-analysis of 11 observational studies (39?141 participants, 6278 fractures, 2367 hip fractures), each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted RR for any fracture of 0.93 (95% CI, 0.89-0.96) and an adjusted RR for hip fracture of 0.80 (95% CI, 0.75-0.86). A meta-analysis of 11 RCTs (34?243 participants, 2843 fractures, 740 hip fractures) of vitamin D supplementation alone (daily or intermittent dose of 400-30?000 IU, yielding a median difference in 25[OH]D concentration of 8.4 ng/mL) did not find a reduced risk of any fracture (RR, 1.06; 95% CI, 0.98-1.14) or hip fracture (RR, 1.14; 95% CI, 0.98-1.32), but these trials were constrained by infrequent intermittent dosing, low daily doses of vitamin D, or an inadequate number of participants. In contrast, a meta-analysis of 6 RCTs (49?282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with vitamin D (daily doses of 400-800 IU, yielding a median difference in 25[OH]D concentration of 9.2 ng/mL) and calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (RR, 0.94; 95% CI, 0.89-0.99) and a 16% reduced risk of hip fracture (RR, 0.84; 95% CI, 0.72-0.97).

Conclusions and relevance

In this systematic review and meta-analysis, neither intermittent nor daily dosing with standard doses of vitamin D alone was associated with reduced risk of fracture, but daily supplementation with both vitamin D and calcium was a more promising strategy.

SUBMITTER: Yao P

PROVIDER: S-EPMC6991219 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis.

Yao Pang P Bennett Derrick D Mafham Marion M Lin Xu X Chen Zhengming Z Armitage Jane J Clarke Robert R

JAMA network open 20191202 12

<h4>Importance</h4>Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness.<h4>Objective</h4>To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation wit ...[more]

PMID: 31860103

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Project description:Background & objectivesCalcium and vitamin D, separately or in combination are usually prescribed to prevent fragility fractures in elderly population. However, there are conflicting results regarding the ideal dosage and overall efficacy obtained from randomized controlled trials (RCTs) conducted in the past. The objective of this study was to assess the fracture risk with the administration of calcium or vitamin D alone or in combination in elderly population (>60 yr).MethodsPubMed, Cochrane and Embase databases were searched to identify the studies from inception to February 2021 with keywords, 'vitamin D', 'calcium' and 'fracture' to identify RCTs. The trials with comparing vitamin D, calcium or combination with either no medication or placebo were included for final analyses. The data were extracted and the study quality was assessed by two reviewers. The principal outcome measure was fractures around hip joint and secondary outcomes assessed were vertebral and any other fracture.ResultsEighteen RCTs were considered for the final analysis. Neither calcium nor vitamin D supplementation was associated with risk of fractures around hip joint [risk ratio (RR) 1.56; 95% confidence interval (CI), 0.91 to 2.69, I[2]=28%; P=0.11]. In addition, the combined administration of calcium and vitamin D was also not associated with fractures around the hip joint in comparison to either no treatment or placebo. The incidence of vertebral (RR 0.95; 95% CI, 0.82 to 1.10, I[2]=0%; P=0.49) or any other fracture (RR 0.83; 95% CI 0.65 to 1.06, I[2]=0%; P=0.14) was not significantly associated with the administration of calcium and vitamin D either individually or in combination. Further subgroup analysis of the results did not vary with the dosage of calcium or vitamin D, dietary calcium intake sex, or serum 25-hydroxyvitamin D levels.Interpretation & conclusionsThe present meta-analysis of RCTs on calcium, vitamin D or a combination of the two in comparison to no treatment or placebo did not support the routine administration protocol of calcium and vitamin D either alone or in combination to lower the risk of fractures in elderly population.

Project description:Importance:The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal. Previous studies have reached mixed conclusions regarding the association between calcium, vitamin D, or combined calcium and vitamin D supplements and fracture incidence in older adults. Objective:To investigate whether calcium, vitamin D, or combined calcium and vitamin D supplements are associated with a lower fracture incidence in community-dwelling older adults. Data Sources:The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to December 24, 2016, using the keywords calcium, vitamin D, and fracture to identify systematic reviews or meta-analyses. The primary randomized clinical trials included in systematic reviews or meta-analyses were identified, and an additional search for recently published randomized trials was performed from July 16, 2012, to July 16, 2017. Study Selection:Randomized clinical trials comparing calcium, vitamin D, or combined calcium and vitamin D supplements with a placebo or no treatment for fracture incidence in community-dwelling adults older than 50 years. Data Extraction and Synthesis:Two independent reviewers performed the data extraction and assessed study quality. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs), and 95% CIs using random-effects models. Main Outcomes and Measures:Hip fracture was defined as the primary outcome. Secondary outcomes were nonvertebral fracture, vertebral fracture, and total fracture. Results:A total of 33 randomized trials involving 51 145 participants fulfilled the inclusion criteria. There was no significant association of calcium or vitamin D with risk of hip fracture compared with placebo or no treatment (calcium: RR, 1.53 [95% CI, 0.97 to 2.42]; ARD, 0.01 [95% CI, 0.00 to 0.01]; vitamin D: RR, 1.21 [95% CI, 0.99 to 1.47]; ARD, 0.00 [95% CI, -0.00 to 0.01]. There was no significant association of combined calcium and vitamin D with hip fracture compared with placebo or no treatment (RR, 1.09 [95% CI, 0.85 to 1.39]; ARD, 0.00 [95% CI, -0.00 to 0.00]). No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration. Conclusions and Relevance:In this meta-analysis of randomized clinical trials, the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. These findings do not support the routine use of these supplements in community-dwelling older people.

Project description:To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence).Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

Dataset Information

Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis.

Importance

Objective

Data sources

Study selection

Data extraction and synthesis

Main outcomes and measures

Results

Conclusions and relevance

Publications

Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis.

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