WASHINGTON – A first-of-its-kind study published in AACC’s Clinical Chemistry journal has found that low vitamin D levels alone do not cause osteoporotic fractures. This research could resolve the longstanding debate over whether vitamin D supplements prevent these fractures, and indicates that members of the general population should not rely on vitamin D by itself for this purpose.

Vitamin D plays a well-known role in helping the body absorb minerals that are essential for bone health. In spite of this, studies have yielded conflicting answers on whether low vitamin D actually increases the risk of osteoporotic fractures—and on whether vitamin D supplements, in turn, can reduce the risk of these fractures. Guidelines on vitamin D reflect this confusion, with the Endocrine Society and American Geriatric Society recommending vitamin D supplementation in older adults to prevent fractures, while the U.S. Preventive Services Task Force recommends against it. Meanwhile, in the absence of clear guidance, vitamin D supplement use in American adults who are 70 years or older has increased almost 100-fold, from 0.4% in 2000 to 38.5% in 2014.

In light of vitamin D’s popularity, a team of researchers led by Børge G. Nordestgaard, MD, of Copenhagen University Hospital in Denmark set out to find more definitive evidence of whether or not this supplement works as a preventive therapy. To do this, the researchers performed the first-ever large-scale analysis of low vitamin D levels and osteoporotic fractures using Mendelian randomization—a genetics-based method designed to overcome the limitations of previous studies on this subject. First, Nordestgaard’s team identified 35,833 individuals who underwent genetic and vitamin D testing between the ages of 20-100 as part of the decades-long Copenhagen City Heart and Copenhagen General Population Studies (which began in 1976 and 2003, respectively). From the genetic testing results, the researchers determined the number of genes each participant had that naturally lower vitamin D levels. Nordestgaard’s team then looked at study participants’ medical records to determine how many of them experienced osteoporotic fractures from 1981-2017.

Using all of this data, the researchers performed a statistical analysis that revealed that individuals with low blood levels of vitamin D (≤ 49.9 nmol/L) had an increased risk for osteoporotic fractures compared to individuals with ≥50 nmol/L of vitamin D. However, to the researchers’ surprise, individuals with high numbers of vitamin D-lowering genes did not have a higher risk of osteoporotic fractures than those with fewer of these genes. When taken together, these two results indicate that low vitamin D does not actually cause osteoporotic fractures and that it might be associated with fractures simply because it is a marker of an overall unhealthy lifestyle.

“Our study is the first large scale study addressing whether vitamin D is causally related to fractures in the general population using genetics—that is, using nature’s own randomized trial free of confounding,” said Nordestgaard. “[It suggests] that vitamin D per se is unlikely to be causally related to fractures. Summing the evidence from previous randomized trials with our new evidence thus suggests that benefit from vitamin D supplementation is likely to prevent osteoporotic fractures only if taken together with calcium.”

About AACC

Dedicated to achieving better health through laboratory medicine, AACC brings together more than 50,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, AACC has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.myadlm.org.

Clinical Chemistry (clinchem.org) is the leading international journal of laboratory medicine, featuring nearly 400 peer-reviewed studies every year that help patients get accurate diagnoses and essential care. This vital research is advancing areas of healthcare ranging from genetic testing and drug monitoring to pediatrics and appropriate test utilization.