NEW YORK (Reuters Health) – A single yearly oral dose of 500,000 international units of cholecalciferol (vitamin D) does not protect generally healthy older women from falls and fractures. On the contrary, it appears to increase the risk of falls and fractures, researchers from Australia found in a double-blind randomized placebo-controlled trial.

“We were very surprised by the findings; we had hypothesized the opposite – that the intervention would reduce falls and fractures. Until further evidence to the contrary is obtained, high-dose vitamin D should be avoided, at least in older women who are not vitamin D deficient,” senior author Dr. Geoff C. Nicholson told Reuters Health by email. His study appears in the May 12 issue of the Journal of the American Medical Association.

“It may also be necessary to reevaluate the risks and benefits of the current clinical practice of providing high loading doses of cholecalciferol to patients who are vitamin D deficient,” said the co-authors of an editorial in the same issue.

Between June 2003 and June 2005, Dr. Nicholson, from Barwon Health and the University of Melbourne in Geelong and colleagues recruited community-dwelling women, aged 70 and older, who were considered to be at high risk for fracture. They randomly assigned 1,131 women to a single oral dose of 500,000 IU of cholecalciferol and 1,127 to placebo, taken in the autumn or winter for 3 to 5 years. “We used the once-a-year regimen to improve compliance, which is typically very poor in vitamin D studies using daily dosing,” Dr. Nicholson said.

The study ended in 2008. All but two women in the placebo arm were included in the primary analysis. A total of 5,404 falls occurred during the study period, with 74% of women in the vitamin D group versus 68% of women in the placebo group falling at least once. Women in the annual high-dose vitamin D group experienced 15% more falls, the investigators note.

Women in the vitamin D group also had more fractures (171 versus 135 in the placebo group); the fracture incidence was 27% higher with annual high-dose vitamin D supplementation.

“The increased likelihood of falls in the vitamin D group was exacerbated in the 3-month period immediately following the annual dose and a similar temporal trend was observed for fractures,” the authors found in a post hoc analysis.

Dr. Nicholson said that in late 2007 — after all the participants in the current study had received their final dose of vitamin D or placebo – trial data from the U.K. provided a “clue” that the high-dose once-a-year regimen might not be safe, at least not for elderly women.

That U.K trial had investigated once-a-year intramuscular injection of vitamin D (ergocalciferol 300,000 IU) in about 9,400 older men and women. “In men, the treatment had no effect on fractures. However, women treated with vitamin D had an increased risk of fractures — up to 1.8-fold for hip/femur fractures,” Dr. Nicholson said.

In their editorial, Dr. Bess Dawson-Hughes and Dr. Susan S. Harris, of Tufts University, Boston, say the findings “raise the possibility that infrequent high doses of vitamin D are counterproductive.”

But they say the findings “do not alter the importance of correcting widespread vitamin D deficiency and insufficiency. There is not evidence for adverse effects of more frequent, lower-dose regimens, so daily, weekly, or monthly dosing with vitamin D3 appears to be the best option for clinicians at this time.”

VITAMIN D PLUS PHYSIOTHERAPY AFTER HIP FRACTURE

Another study published May 10 in Archives of Internal Medicine also found no benefit of vitamin D in preventing falls – but it still showed that the combination of 2000 IU/day cholecalciferol plus extended physiotherapy may benefit elderly hip fracture patients.

In this study, vitamin D helped reduce hospital readmission but not falls, and physical therapy (PT) helped reduce falls but not hospital readmission.

Using a factorial design, the researchers randomly allocated 173 seniors (79.2% women; mean age, 84) to cholecalciferol (800 or 2000 IU/day) and extended physiotherapy (supervised 60 min/day during acute care plus a simple unsupervised home program) or standard PT (supervised 30 min/day during acute care plus no home program).

The higher-dose vitamin D did not significantly reduce the rate of falls compared to the standard-dose, but it did reduce hospital re-admission by 39% in the first year after hip fracture.

“This was mostly driven by a significant 60% reduction in fall-related injury (largely re-fracture) and a significant 90% reduction in severe infections that led to re-admission to acute care,” first author Dr. Heike A. Bischoff-Ferrari from the University of Zurich told Reuters Health by email.

The extended physiotherapy program, on the other hand, did not reduce the rate of hospital readmissions but it did reduce the rate of falls by 25% overall and by 36% among those who did PT at home at least once per week compared to those who did not do PT at home once per week or were randomized to standard PT.

“To date, we have no guidelines how to treat senior patients with hip fractures,” Dr. Bischoff-Ferrari told Reuters Health. The current study, the researcher said, suggests that home physiotherapy plus higher-dose vitamin D “should be used together as they have a significant but differential benefit on complications after hip fracture.”

These two interventions, the study team notes, are “practical, well tolerated in elderly patients with hip fractures and multiple comorbidities, and relatively low in cost.” Moreover, the effect sizes demonstrated on falls and hospital readmission are “clinically meaningful.”

At baseline, a little more than half of participants had severe vitamin D deficiency (25-hydroxyvitamin D level < 12 ng/mL); 97.7% had 25(OH)D level < 30 ng/mL. Both dosages eradicated the severe deficiencies. In addition, by 12 months 70% of participants in the 800-IU/day arm and 93% in the 2000-IU/day arm reached desirable levels of at least 30 ng/mL. Commenting on the results of the JAMA study, which failed to show a benefit and suggested harm of a single annual 500,000 IU cholecalciferol dose in healthy elderly, Dr. Bischoff-Ferrari said: “One concern may be that the once-per year high-dose application of vitamin D does not provide a stable vitamin D level during all months of the year.” Reference:
JAMA 2010;303:1815-1822,1861-1826.
Arch Intern Med 2010;170:813-820.