Does Vitamin D Lower Fracture Risk?

Start with the Guideline Recommendations for Vitamin D in Osteoporosis

In 2010, Osteoporosis Canada published the 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary in CMAJ.  They made the following recommendations for vitamin D and calcium use:1

  • The total daily intake of elemental calcium (through diet and supplements) for individuals over age 50 should be 1200 mg
  • For healthy adults at low risk of vitamin D deficiency, routine supplementation with 400–1000 IU (10–25 μg) vitamin D3 daily is recommended
  • For adults over age 50 at moderate risk of vitamin D deficiency, supplementation with 800–1000 IU (20–25 μg) vitamin D3 daily is recommended. To achieve optimal vitamin D status, daily supplementation with more than 1000 IU (25 μg) may be required. Daily doses up to 2000 IU (50 μg) are safe and do not necessitate monitoring
  • For individuals receiving pharmacologic therapy for osteoporosis, measurement of serum 25-hydroxyvitamin D should follow three to four months of adequate supplementation and should not be repeated if an optimal level (≥ 75 nmol/L) is achieved

New Studies Provide Some Guidance on Vitamin D

A couple of papers were published last year that provide some guidance on the potential role of vitamin D in osteoporosis prevention. These include:

Does High-Dose Vitamin D Work Better than Low-Dose?

The first paper was a RCT evaluating the impact of high-dose vitamin D3 supplementation (4000IU, 10,000IU) compared to standard dose (400IU) on bone mineral density (BMD) in the radius and tibia over 3 years.2  Calcium supplementation was provided to participants with dietary intake of less than 1200mg per day.2 Higher doses did not perform well:

  • Radial BMD
    • -1.2% for the 400IU/day group
    • -2.4% for the 4000IU/day group
    • -3.6% for the 10,000IU/day group
  • Tibial BMD
    • -0.4% for the 400IU/day group
    • -1.0% for the 4000IU/day group
    • -1.7% for the 10,000IU/day group

The authors concluded that high dose vitamin D significantly decreased BMD over 3 years compared to 400IU.  They state there was no benefit of high-dose and further research should be done to evaluate if these doses are harmful.

Does Vitamin D Reduce the Risk of Fractures?

The second paper performed a systematic review and meta-analysis to evaluate if vitamin D and calcium prevent fractures.3 They analyzed observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included.3 Randomized clinical trials compared vitamin D or vitamin D and calcium with control.3

Here are the main findings:3

  • Each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted relative risk (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)
  • 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
  • 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- 1200mg) 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).

The findings of this review are that vitamin D supplementation alone is unlikely to have an impact on fracture risk reduction, but that the combination of vitamin D with calcium may reduce fractures.

What Does this Mean for Practice?

  • High dose vitamin D supplementation appear to worsen BMD compared to standard dosing of 400IU per day
  • Vitamin D supplementation alone does not appear to reduce the overall fracture risk
  • A combination of vitamin D and calcium supplementation are associated with a lower risk of any or hip fracture
  • Clinicians should encourage patients to supplement their dietary calcium intake to a maximum of 1200 mg of elemental calcium
    • Remember higher doses of calcium have been associated with a potential increased risk of cardiovascular events4

References

  1. Papaioannou A, Morin S, Cheung AM, et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ. 2010;182(17):1864-1873. doi:10.1503/cmaj.100771
  2. Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA. 2019;322(8):736-745. doi:10.1001/jama.2019.11889
  3. Yao P, Bennett D, Mafham M, et al. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019;2(12):e1917789-e1917789. doi:10.1001/jamanetworkopen.2019.17789
  4. Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart. 2012;98(12):920-925. doi:10.1136/heartjnl-2011-301345

 

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