Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis
Yao P, Bennett D, Mafham M, Lin X, Chen Z, Armitage J, Clarke R
JAMA network open · 244 citations
How it was studied
- Design
- Meta-analysis (indexed by PubMed)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- Medical Research Council
- Grants
- Medical Research Council (MC_UU_00017/1)
Based on 1 listed funder(s).
Publication
- Published
- 2019-12-20 · JAMA Netw Open · vol. 2 · issue 12 · p. e1917789
- Publisher
- American Medical Association
- Cited
- 348 citations · more than 100% of similar papers · 22.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 73 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Vitamin D Research Studies · Bone health and osteoporosis research · Vitamin C and Antioxidants Research
- Keywords
- Observational study, Medicine, Randomized controlled trial, Vitamin D and neurology, Meta-analysis, Hip fracture, Cochrane Library, Internal medicine, Relative risk, Physical therapy, Osteoporosis, Confidence interval
- MeSH
- bone and bones, humans, hip fractures, calcitriol, vitamin d, dietary supplements, bone density conservation agents, fractures, bone, randomized controlled trials as topic
7 authors
From GB, CN
- Pang YaoUniversity of Oxford
- Derrick BennettUniversity of Oxford
- Marion M. MafhamUniversity of Oxford
- Xu LinChinese Academy of Sciences; Shanghai Institute of Nutrition and Health
- Zhengming ChenUniversity of Oxford; Medical Research Council
- Jane ArmitageUniversity of Oxford; Medical Research Council
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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