From American Society for Bone and Mineral Research (ASBMR) 30th Annual Meeting

September 15, 2008 (Montreal) — Total and supplemental use of vitamin C — but not dietary vitamin C intake — are associated with a reduced risk for hip and nonvertebral fracture, according to research presented here on September 14 at the American Society for Bone and Mineral Research 30th Annual Meeting.

"We want to look at modifiable risk factors [for osteoporosis], and diet is so modifiable," coauthor and presenter Marian T. Hannan, DSc, MPH, told Medscape Diabetes & Endocrinology. "Vitamin C [intake] is highly modifiable. It's a water-soluble vitamin that's easily digested and easily absorbed.... [In addition,] there's a pathway for antioxidants inhibiting bone resorption.... There's [also] a collagen effect that's directly related to vitamin C." Dr. Hannan is a senior scientist and codirector of musculoskeletal research at the Institute for Aging Research at Hebrew Senior Life, Boston, Massachusetts. She is also an associate professor of medicine at Harvard Medical School in Boston.

Lead author Shivani Sahni, PhD, and colleagues evaluated the correlation between vitamin C intake — total, dietary, and supplemental — and incident hip and nonvertebral fracture among 958 individuals participating in the Framingham Osteoporosis Study, for which participants began completing food frequency questionnaires in 1988 to 1989. The participants were followed up for hip fracture until 2005 and for nonvertebral fracture until 2003. Dr. Sahni is a postdoctoral fellow in aging at Hebrew Senior Life. She conducted the study while a doctoral student at Tufts University in Boston.

Overall, 100 participants experienced a hip fracture and 180 participants a nonvertebral fracture during the study period. Those in the lowest tertile (tertile 1) for total and supplemental vitamin C intake experienced significantly more hip and nonvertebral fractures than those in the highest tertile (tertile 3). This remained the case after controlling for sex, age, body mass index, height, smoking, physical activity, total energy intake, and bone mineral density, as well as intake of estrogen (for women), multivitamins, and potassium.

Total vitamin C intake was an average of 97 mg/day among those in the lowest tertile and 305 mg/day for those in the highest. The P for trend across the 3 tertiles for both hip and nonvertebral fractures was .04 (hip fracture, tertile 2, hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.45 – 1.20; hip fracture, tertile 3, HR, 0.56; 95% CI, 0.31 – 0.98; nonvertebral fracture, tertile 2, HR, 0.98; 95% CI, 0.68 – 1.40; nonvertebral fracture, tertile 3, 0.64; 95% CI, 0.42 – 0.99). For supplemental vitamin intake, which ranged from an average of 0 mg/day to 260 mg/day across the 3 tertiles, the P for trend was .02 for hip fracture (tertile 2, HR, 0.50; 95% CI, 0.20 – 1.24; tertile 3, HR, 0.31; 95% CI 0.13 – 0.73) and .06 for nonvertebral fracture (tertile 2, HR, 0.81; 95% CI, 0.38 – 1.73; tertile 3, 0.58; 95% CI, 0.30 – 1.11).

"Basically, people who had higher levels of vitamin C intake had half the rate of hip fractures as people who had the lowest vitamin C [levels]," said Dr. Hannan. "Similarly, people who took supplemental vitamin C again had roughly half the amount of hip fractures as people who did not take any supplemental vitamin C."

The association was not seen when dietary vitamin C intake alone was evaluated. Dr. Hannan says this is not surprising. "It mimics what we see when we look at vitamin D, and we know that vitamin D is associated with bone health," she said. "The vitamin C levels that elderly men and women consume in the United States, they're okay, but they're not great, and they're not optimal."

Mary S. Anthony, PhD, an adjunct professor of medicine at Wake Forest University in Winston-Salem, North Carolina, and director of global epidemiology for Amgen in Thousand Oaks, California, moderated the session. She was also not surprised that dietary vitamin C intake did not predict fractures. "The values of dietary vitamin C may be too low," she told Medscape Diabetes & Endocrinology. "[In addition,] dietary intake varies a lot during the year,...but you get a constant amount from supplements." The results might also reflect the limitations of food frequency questionnaires, she said.

These findings suggest the need to take vitamin C intake into account in the clinical setting. "All the data that we have thus far is on observational cohorts," said Dr. Hannan. "I wouldn't recommend to physicians yet...to check patients' vitamin C [or] give them something that increases their vitamin C. On the other hand,...there's a wealth of evidence that supports it. It's not just shooting in the dark. It's pretty well-based that one should pay attention to it."

Dr. Anthony would go a little further, "given that vitamin C seems relatively safe and beneficial for other things as well, then I think that advising people to eat more fruits and vegetables and maybe take a multivitamin or [vitamin C] supplements [is a good idea].... While I wouldn't recommend that people stop taking a physician-prescribed medication for bone loss and instead take vitamin C, as a first line of defense we should always be looking toward nutritional ways to promote health before moving toward medicines."

The study did not receive commercial support. Dr. Sahni and Dr. Hannan have disclosed no relevant financial relationships.

American Society for Bone and Mineral Research 30th Annual Meeting: Abstract 1186. Presented September 14, 2008.

Pearls for Practice

• Intake of total and of supplemental — but not dietary — vitamin C in tertile 2 in older patients is associated with 27% and 50% reduction, respectively, in the rate of hip fractures, whereas in tertile 3, the rate was 54% and 69%, respectively.
• Daily intake of total vitamin C in the lowest and highest tertiles is 97 and 305 mg/day, respectively, and daily intake of supplemental vitamin C ranges from 0 to 260 mg/day.

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