The U.S. Preventive Services Task Force (USPSTF) recently posted their draft research plan on vitamin D and/or calcium supplementation for primary prevention of fractures in adults, and requested the Vitamin D Council’s feedback.
The USPSTF is a panel of physicians and epidemiologists appointed by the US Department of Health and Human Services. They publish recommendations for a variety of different things after evaluating the effectiveness of interventions, screening and other clinical practices.
The draft research plan on vitamin D and/or calcium supplementation purpose is to gather comments from the public before releasing a finalized recommendation six months later. It identifies study characteristics and criteria that they will use to find studies to be included in their review.
The Vitamin D Council was more than happy to use this opportunity for our voices to be heard. Take a look below to read our response.
April 14, 2016
Dear Sir or Madam:
The Vitamin D Council believes that in 2013, the USPSTF overlooked a few crucial studies that illustrate the significant role vitamin D plays in fracture prevention. In 2013, the USPSTF concluded that there is inadequate research to support vitamin D supplementation among post-menopausal women, premenopausal women and men. This year, the Vitamin D Council hopes that the USPSTF will take the following recommendations into consideration before making their final statement.
As the USPSTF is well aware, clinical trials provide the strongest findings due to their ability to prove causation. However, when one evaluates the quality of a clinical trial, there are several things to keep in mind. First, are all subjects enrolled into the trial considered vitamin D deficient? What is the point in giving vitamin D to a treatment group that is already sufficient? Second, is the dosage large enough to make a significant impact on their vitamin D levels? In order to evaluate the effectiveness of supplementation, the majority of the participants must reach a sufficient vitamin D status by the end of the study. Normally, this requires a dosage equivalent of at least 800 IU daily. Lastly, the study’s population should be at risk for the outcome that the study is evaluating. In order to produce significant results, a proportion of the study population must experience the outcome, such as fractures. Researchers are unable to compare two groups if neither experience the outcome.
This leads me to request the inclusion of several relevant clinical trials into USPSTF’s research analysis:
- Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial
- Vitamin D3 and calcium to prevent hip fractures in the elderly women
- Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomized double blind controlled trial
These studies consist of experimental groups that were given the equivalent of at least 800 IU daily and control groups that were given a matching placebo. All studies concluded that vitamin D supplementation prevented fractures. However, all study populations involved an elderly population, because as explained earlier, the study population must be at risk for the outcome to produce significant results. Because of the difficulty in conducting a well-designed clinical trial using a population not at risk for fractures, researchers have not investigated the effects of vitamin D supplementation for prevention of fractures in younger populations. The Vitamin D Council believes the lack of clinical trials for younger populations led the USPSTF to recommend against vitamin D supplementation in premenopausal women, post-menopausal women and men. Though, the USPSTF should consider the results from observational studies that include these specific study populations, such as the following:
Women during menopausal transition
Serum 25 Hydroxyvitamin D, Bone Mineral Density and Fracture Risk Across the Menopause
Serum levels of 25-hydroxyvitamin D and functional outcome among postmenopausal women with hip fracture
General Population (mean age 43)
Association of Vitamin D With Stress Fractures: A Retrospective Cohort Study
The observational studies noted found a significant inverse relationship between vitamin D levels and fractures, indicating low vitamin D levels are associated with an increased risk for fractures.
In summary, clinical trials have determined that vitamin D supplementation reduces fracture risk in the elderly if adequate doses are used. Clinical trials have yet to determine the effects of vitamin D supplementation in populations who are not at risk for fractures. Though, current evidence from observational studies suggests that low vitamin D levels are associated with higher risk of fractures in younger populations. The Vitamin D Council, therefore, believes if the USPSTF recommends against vitamin D supplementation for the prevention of fractures, they may be doing more harm than good. Vitamin D supplementation is generally safe when used in appropriate dosages. A recent study illustrated the safety of vitamin D in comparison to Tylenol, showing vitamin D is much less harmful than Tylenol.
It is important to remember that vitamin D and calcium are not the sole factors in the prevention of fractures, although some research suggests that vitamin D supplementation alone will likely aid in fracture prevention. But vitamin D does not work in a vacuum. For example, magnesium was found in a controlled trial to increase bone density. Likewise, vitamin K has favorable effects on bone. Silicon and boron are also found in bone. Higher dietary intake of vitamins A, C and E, β-carotene, and Se are associated with reduced fracture risk.
Thus, the Vitamin D Council predicts studies using only one nutrient, vitamin D, in a low dose, will not reduce fractures.
We suggest you use the Heaney criteria in evaluating studies, which are the population studied must be at an elevated risk for fracture, baseline vitamin D must be below 20 ng/ml, placebo group must remain below 20 ng/ml during the trial, final 25(OH)D should exceed 40 ng/ml in the treatment group, baseline and final 25(OH)D must be obtained in all subjects, and the nutrient’s co-factors should be given with the nutrient.
Tovey, A. & Cannell, JJ. Comment on USTSPF drafted research plan. The Vitamin D Council Blog & Newsletter, 2016.
Flicker L, MacInnis RJ, Stein MS, et al. Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. J Am Geriatr Soc. 2005;53(11):1881-1888. doi:10.1111/j.1532-5415.2005.00468.x.
 Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992;327(23).
 Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326(7387):469. doi:10.1136/bmj.326.7387.469.
 Cauley J a., Greendale G a, Ruppert K, et al. Serum 25 Hydroxyvitamin D, Bone Mineral Density and Fracture Risk Across the Menopause. J Clin Endocrinol Metab. 2015;(March):jc.2014-4367. doi:10.1210/jc.2014-4367.
 Liu L-M, Wang S-H, Fu C-S, Han X-Z, Wei B-F. Serum levels of 25-hydroxyvitamin D and functional outcome among postmenopausal women with hip fracture. PLoS One. 2015;10(1):e0116375. doi:10.1371/journal.pone.0116375.
 Miller JR, Dunn KW, Ciliberti LJ, Patel RD, Swanson B a. Association of Vitamin D With Stress Fractures: A Retrospective Cohort Study. J Foot Ankle Surg. 2015:1-4. doi:10.1053/j.jfas.2015.08.002.
 Spiller H, Good T, Spiller N, Aleguas a. Vitamin D exposures reported to US poison centers 2000-2014: Temporal trends and outcomes. Hum Exp Toxicol. 2015:1-5. doi:10.1177/0960327115595685.
 Stendig-Lindberg G, Tepper R, Leichter I.Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnes Res. 1993 Jun;6(2):155-63.
 Sun LL et al. Associations between the dietary intake of antioxidant nutrients and the risk of hip fracture in elderly Chinese: a case-control study. Br J Nutr. 2014 Nov 28;112(10):1706-14.
 Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013 Sep;24(9):2499-507.
 Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev. 2014 Jan;72(1):48-54.