BACKGROUND AND PURPOSE:

• Yao et al. (JAMA Network Open, 2019) assessed the risks of fracture associated with 25-hydroxyvitamin D (25[OH]D) alone or in combination with calcium

METHODS:

• Systematic Review and Meta-Analysis (through December 2018)
• Data sources
  • PubMed, EMBASE, Cochrane Library, and other RCT databases
• Inclusion criteria
  • Observational studies: Minimum 200 fracture cases
  • RCTs: Minimum 500 participants and reporting at least 10 incident fractures | Must have compared vitamin D or vitamin D and calcium with control
• Study design
  • Two researchers independently extracted data and assessed possible bias
  • Rate ratios (RRs) were estimated using fixed-effects meta-analysis
• Primary outcome
  • Any fracture and hip fracture

RESULTS:

Meta-analysis of observational studies: 11 met inclusion criteria

• Each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with
  • Any fracture: Adjusted RR of 0.93 (95% CI, 0.89 to 0.96)
  • Hip fracture: Adjusted RR of 0.80 (95% CI, 0.75 to 0.86)

Meta-analysis of RCTs of vitamin D supplementation alone: 11 met inclusion criteria

• Total of 34,243 participants | 2843 fractures | 740 hip fractures
• There was no reduction in risk of hip or any fracture with vitamin D supplementation alone
  • Any fracture: RR of 1.06 (95% CI, 0.98 to 1.14)
  • Hip fracture: RR of 1.14 (95% CI, 0.98 to 1.32)
  • Quality of data limited: Infrequent intermittent dosing | Low daily doses of vitamin D | Inadequate number of participants

Meta-analysis of RCTs of vitamin D and calcium supplementation: 6 met inclusion criteria

• Total of 49,282 participants | 5449 fractures | 730 hip fractures
• Combined supplementation with vitamin D (daily doses of 400 to 800 IU) and calcium (daily doses of 1000 to 1200 mg) led to a reduced risk of hip and any fracture
  • Any fracture: RR 0.94 (95% CI, 0.89 to 0.99)
  • Hip fracture: RR, 0.84 (95% CI, 0.72 to 0.97)

CONCLUSION:

• Supplementation with standard doses of vitamin D alone did not reduce risk of fracture
• 7 large RCTs  are currently ongoing using higher doses of vitamin D (mean daily dose 2094 IU)
  • Authors stress the importance of waiting for these results before drawing conclusion regarding use of vitamin D alone and fracture risk
• However, in this current study, daily supplementation with vitamin D and calcium reduced risk of hip fracture by 16% and any fracture by 6%
• Authors caution that there are potential risks associated with supplementation
  • Combined vitamin D plus calcium is associated with cardiovascular disease
  • Kidney stones can result from excess calcium intake

Learn More – Primary Sources:

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

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Results from the VITAL Trial: Does Vitamin D Reduce Cardiovascular and Cancer Risk in the General Population?