Vitamin D supplementation did not significantly reduce fracture risk in middle-aged and older adults compared to placebo, according to an additional study from the Vitamin D and Omega-3 (VITAL) Study.
Data showed that taking 2,000 IU of supplemental vitamin D each day without concomitant calcium supplementation did not significantly affect fractures outside the spine (hazard ratio [HR]0.97; P = 0.50), hip fractures (HR 1.01; P = 0.96) or total fractures (HR 0.98; P = 0.70) compared with placebo among those who did not have osteoporosis , vitamin D deficiency, or low bone mass, reports Meryl S. LeBoff, MD, professor of medicine at Harvard Medical School and head of calcium and bone at Brigham and Women’s Hospital in Boston, Massachusetts, and her colleagues.
The results were published July 27 in The New England Journal of Medicine.
Previous randomized controlled trials have produced inconsistent results. Some have shown there is some benefit from supplemental vitamin D, while others have shown no effect or even harm on fracture risk, LeBoff noted.
“Due to conflicting data at the time, we tested this hypothesis to advance the science and understand the effects of vitamin D on bones. In a previous study, we did not observe an effect of vitamin D supplementation on bone density in a subset of the VITAL study,” LeBoff told Medscape Medical News.
“We previously reported that vitamin D, around 2,000 units per day, did not increase bone density or affect bone structure, according to PQCT. [peripheral quantitative CT]. So it was an indication that since bone density is a surrogate marker for fractures, fractures may not be affected in any way,” she added.
These results should dispel any notion that vitamin D alone can significantly reduce fracture rates in the general population, note Stephen R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD. , from the Maine Medical Center Research Institute. Scarborough, in an accompanying editorial.
“Adding these findings to previous reports from VITAL and other studies showing no effect in preventing multiple conditions suggests that health care providers should stop screening for 25-hydroxyvitamin D levels or recommend vitamin D supplements and people should stop taking vitamin D supplements in order to prevent serious disease or prolong life,” the authors write.
The researchers evaluated 25,871 participants from all 50 states over a mean follow-up of 5.3 years. Participants were randomly assigned in a 1:1 ratio to either placebo or vitamin D.
The average age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were black. The participants did not have low bone mass, vitamin D deficiency, or osteoporosis.
Participants agreed not to supplement their diet with more than 1,200 mg of calcium per day and no more than 800 IU of vitamin D per day.
Participants completed detailed questionnaires to assess baseline prescription drug use, demographic factors, medical history, and intake of supplements such as fish oil, calcium, and vitamin D during the preparatory phase. Annual surveys were used to assess side effects, adherence to study protocol, falls, fractures, physical activity, osteoporosis and related risk factors, onset of serious illness, and use of untested prescription drugs and supplements such as vitamin D and calcium.
The researchers assessed fracture incident data using a central review of medical records. To approximate therapeutic effect in the intention to treat analysis, they used proportional hazard models.
Notably, the results were similar for the placebo and vitamin D groups with respect to the occurrence of kidney stones and hypercalcemia.
The effect of vitamin D supplementation was independent of baseline parameters such as race or ethnicity, gender, body mass index, age, or blood levels of 25-hydroxyvitamin D.
Cummings and Rosen note that these results, along with other data from the VITAL study, show that no subgroup classified based on baseline levels of 25-hydroxyvitamin D, including those with levels <20 ng/mL, benefited from vitamin supplementation. .
“There is no basis for measuring 25-hydroxyvitamin D levels in the general population or treating to target serum levels. 25-hydroxyvitamin D levels may be a useful diagnostic test for some patients with conditions that may or may cause severe deficiency,” the authors note.
Rosen and Cummings write that, with the exception of individual patients, such as people living in nursing homes, who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D insufficiency” must now be reconsidered.
The researchers note that study limitations include evaluating only one dose of vitamin D supplementation and not adjusting for multiplicity, exploratory, parental trials, or secondary endpoints.
The number of participants with vitamin D deficiency was limited due to ethical and practical considerations for these patients. The researchers write that the data cannot be generalized to institutionalized older adults or those with osteomalacia or osteoporosis.
“The interpretation of this [study] I don’t think vitamin D is for everyone,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and head of endocrinology at University Hospital in Cleveland, Ohio, who was not involved in the study.
“This is not the last word; I would advise you not to shower everyone with vitamin D. I would use bone formation markers as the best indicator to determine if they need vitamin D or not, especially looking at parathyroid hormone.” Arafah said in a telephone interview.
Arafa pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message. If you read the article, you will find that there are people who really need vitamin D; people with a deficiency do need vitamin D. There is no doubt that excessive or extreme levels of vitamin D deficiency can lead to other things, particularly osteomalacia, bone weakness, [and] poor mineralization, so we’re not really safe at the moment.”
An additional study from the VITAL study was sponsored by the National Institute of Arthritis, Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the study. LeBoff reveals that he owns shares in Amgen. Cummings reports personal fees and non-financial support from Amgen in addition to the submitted work. Rosen is Associate Editor of The New England Journal of Medicine. Arafah reports that there is no relevant financial relationship.
N Engl J Med. Posted online July 27, 2022 Editorial Abstract
Ashley Liles is an award-winning medical journalist. She is an alumnus of New York University’s Science, Health, and Environment Reporting Program. Her work has appeared in The New York Times Daily 360, PBS NewsHour, The Huffington Post, Undark, The Root, Psychology Today, Insider and Tonic (Health by Vice) and other publications.
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