Vitamin D and fracture prevention

Clinical question

Do vitamin D supplements prevent fragility fractures?

Bottom line

Vitamin D supplementation alone does not prevent fractures regardless of dose, baseline vitamin D level, or previous fractures. The combination of calcium and vitamin D might reduce the total risk of fractures from 11.5% to 10.9% and risk of hip fractures from 1.8% to 1.5% over 9 to 84 months, but this benefit may be limited to women in long-term care. Adding calcium increases risk of renal calculi (2.1% to 2.5%).

Evidence

Results are statistically significant unless indicated. Eight systematic reviews^1-8 of 7 to 36 RCTs were consulted of about 34,000 to 76,000 mostly community-dwelling women, some with previous fracture, established osteoporosis, or metabolic bone disease. After 9 to 84 months:

• Vitamin D versus placebo or no treatment:

  • - No difference in total fracture^1-8 and no difference in hip fracture.^1-5,8 One systematic review⁷ (varying high doses) suggested slightly higher risk in women (1.2% vs 0.9%).

  • - Total or hip fractures:

    • — High dose (>800 IU): Three systematic reviews showed no difference,^1,4,8 1 showed increased risk (described above),⁷ and 1 showed benefit,⁶ but no absolute numbers reported.

    • — Baseline vitamin D level of less than 50 nmol/L¹ or previous fracture²: No difference.

• Vitamin D–calcium combination versus placebo:

  • - Total fracture: 10.9% versus 11.5% (placebo), number needed to treat (NNT)=167.² Others showed similar results.^3,5,6 One systematic review did not report the largest RCT.¹

    • — After removing 2 RCTs of women in long-term care, results were no longer statistically different.²

  • - Hip fracture²: 1.5% versus 1.8% (placebo), NNT=333.

    • — Two systematic reviews found similar results^3,5; 1 found no difference.⁸

  • - Total or hip fracture:

    • — Baseline vitamin D level of less than 50 nmol/L or previous fracture^1,2: No difference.

• There were no adverse events with vitamin D alone.² For combination with calcium, there was no difference in mortality or gastrointestinal effects² but renal calculi increased (2.5% vs 2.1% with placebo).⁷

• Limitations include smaller positive studies skewing results toward favouring vitamin D.^2,4 Randomization processes and concealment were unclear.²

Context

• Calcium alone does not affect total or hip fracture risk.^1,8

• Measuring vitamin D levels routinely is unnecessary. No RCTs have evaluated treating to a target vitamin D level to prevent fractures.⁹

Implementation

Supplementation with vitamin D and calcium is unlikely to have clinically important benefits if the diet contains adequate calcium.¹⁰ The only group that has RCT evidence of potential benefit from vitamin D–calcium supplementation for preventing fractures are women in long-term care. Screening for fracture risk can be done with a Fracture Risk Assessment Tool score to estimate 10-year fracture risk, followed by a dual-energy x-ray absorptiometry scan if the patient would consider anti-resorptive therapy (eg, bisphosphonates).¹¹ Other therapies include balance training exercises to reduce falls and resistance training to improve physical functioning.¹⁰