Vitamin D Supplementation for Bone Health

A recent study showed that supplementation with higher doses of vitamin D did not improve bone mineral density and strength in otherwise healthy adults.

Consultant360 spoke with Co-Principal Investigator, David Hanley, MD, FRCPC, Professor Emeritus in the Departments of Medicine, Oncology, and Community Health Sciences at the University of Calgary, about the study findings and what they mean for clinical practice.

Consultant360: How did you decide on the topic of your research?

David Hanley: At the time we were planning the study, there was persistent debate as to the potential benefits of higher than standard Health Canada recommendations for vitamin D intake established by the 2011 Institute of Medicine (IOM [now known as The Academy of Medicine]) report on Dietary Reference Intakes for Calcium and Vitamin D. Some experts advocated higher doses for optimal skeletal benefits as well as non-skeletal benefits such as prevention of autoimmune disorders and cancers. It has been reported that 3% of Americans consume daily doses greater than the IOM’s Tolerable Upper Intake Level (TUL) of 4000 IU/day. A TUL may be defined as the maximum dose that can be considered to be safe for the majority of the population, i.e. can be taken without medical monitoring. Some experts had suggested that the TUL for Vitamin D should be 10,000 IU/day.

Our research group has expertise in the use of High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) of the distal radius and tibia, a highly sensitive measurement of true volumetric bone density. Our HR-pQCT provides a 3-dimensional image of bone architecture down to a resolution of 60 microns, and this allows computer modeling assessment of strength. Because bone is the tissue that is best recognized and documented as a target for vitamin D action, we wished to determine if HR-pQCT could demonstrate a further benefit of higher doses of vitamin D that might not be identified by routine measurements of areal bone density by dual X-ray absorptiometry (DXA). We hypothesized that high dose vitamin D might suppress bone turnover and be associated with a slowing of age-related bone loss. We thought a 3-year study of high dose vitamin D (4000 IU/day or 10,000 IU/day) vs standard dose (400 IU/day) would be long enough to see if bone changes could persist beyond transient changes that might occur in the first 6- 12 months. Rather than having a placebo arm of the study we used the subjects receiving 400 IU/day as a reference group. Based on dietary studies in the USA and Canada the 400 IU group would be assumed to receive an average of about 200 IU from diet, which would bring them up to the 600 IU/day recommended by the IOM for adults up to age 70 years.

C360: What were the key findings of your research?

DH: The most important finding was that, in these healthy subjects who did not have vitamin D deficiency, 400 IU vitamin D daily maintained a normal blood 25-OH vitamin D, and the use of vitamin D doses of 4000 or 10,000 IU/day did not offer any additional bone health benefit.

Instead of the hypothesized benefit, both the 4000 and 10,000 IU groups had a greater loss of volumetric bone density as measured by HR-pQCT than the 400 IU group. This increased rate of loss was significant for the 10,000 IU group at both the radius and tibia, and for the 4000 IU group only at the radius. Actual rates of change in volumetric density over 3 years were modest: mean percent changes in volumetric BMD at the radius were -1.2% (400 IU group), -2.4% (4000 IU group) and -3.5% (10,000 IU group); and at the tibia, -0.4% (400), -1.0% (4000) and -1.7% (10,000).

Although the HR-pQCT measured bone density loss raises the possibility of skeletal harm, there was no significant difference in calculated bone strength among the 3 dose groups. Similarly, there was no difference between the groups with respect to DXA bone density.

The 3 doses of vitamin D were generally well tolerated. Hypercalciuria was seen in all subject groups but there was a relationship to vitamin D dose, with the greatest frequency in the 10,000 IU group.

C360: How will the findings impact clinical practice and what is the takeaway for our audience?

DH: The takeaway message is that, for healthy adults who are vitamin D sufficient while taking 400 IU daily, there is no further bone benefit to be derived by increasing the vitamin D dose. In this study, 400 IU Vitamin D per day for 3 years maintained a serum 25-OH vitamin D well above the 20 ng/mL (50 nmol/L) level that the IOM report has suggested would represent adequate vitamin D nutrition for 97.5% of the population.

The greater loss of HR-pQCT measured bone density with the higher doses of vitamin D raises the question of harm, but this possibility requires further confirmation with a randomized clinical trial to test that hypothesis.

C360: What knowledge gaps still exist in this area of medicine?

DH: We undertook this study with the hypothesis that high dose vitamin D might be associated with an increase in HR-pQCT bone density and bone strength. Because we found the opposite effect to our hypothesis, the correct interpretation is that further studies are necessary before we can be certain that higher doses are harmful to bone. If 10,000 IU vitamin D/day might be a stimulus to bone loss, the mechanism is not clear, and it should also be pointed out that the bone loss demonstrated in this study was not associated with a loss of estimated strength. It is interesting to note, however, there have been 2 randomized clinical trials of huge intermittent doses of vitamin D (300,000 and 500,000 IU once yearly) that have actually been associated with increased risk of falls or fractures.^1,2

This study did not address any of the other postulated non-skeletal benefits of vitamin D, such as reduced risk of auto-immune diseases or some cancers. It is possible that these benefits, if present, might require higher doses of vitamin D than the amount that seems to be adequate for bone. 

 References:

1. Smith H, Anderson F, Raphael H, et al. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Rheumatology (Oxford). 2007 Dec;46(12):1852-7.
2. Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010 May 12;303(18):1815-2