The risk of sustaining a hip fracture is two to four times higher among patients who have suffered a stroke than among age-matched, healthy controls because of frequent falls and osteoporosis. A new study appearing in the March 2nd issue of the Journal of the American Medical Association (JAMA) shows, however, that daily supplementation with 5 mg of folic acid and 1500 µg of vitamin B12 (mecobalamin) may reduce the risk of hip fractures among stroke patients by as much as five-fold.1
The study also demonstrated that the use of B-vitamins suppresses levels of homocysteine, an amino acid thought to interfere with the development of bone microarchitecture and increase the risk of hip fracture. The authors suggest that this effect accounts for the reduced incidence of hip fracture. "Folate and vitamin B12 may be of benefit to all stroke patients," author Yoshihiro Sato, MD, PhD, a neurologist at the Mitate Hospital in Tagawa, Japan, tells CIAOMed.
Other scientists agree that the treatment shows considerable promise. "The study shows a clear difference in fracture incidence between patients who receive folate/mecobalamin treatment and placebo," says Joyce B.J. van Meurs, PhD, of the department of internal medicine at Erasmus Medical Center in Rotterdam, the Netherlands, and co-author of an editorial accompanying the new study.2
"There are more studies needed to confirm this finding, but, if these results hold, this would add an effective, safe, and cheap treatment for fracture prevention without adverse side effects," Dr. van Meurs tells CIAOMed, adding that "since these supplements are thought be beneficial without any adverse effect, I would suggest giving them to [stroke] patients."
In the single-site, double-blind, randomized controlled study of Japanese patients at high risk for fracture, 314 patients received daily B-vitamins and 314 received a placebo. Patients were aged 65 or older with residual hemiplegia at least 1 year following their first ischemic stroke. Because the rate of falling between the groups was a potential confounding factor, study participants kept track of falls on a daily calendar, and reported this information in monthly doctor visits.
Although there was a similar number of falls in each group, during the 2-year study period there were six hip and eight total fractures in patients who used folate and vitamin B12, and 27 hip and 32 total fractures in patients who received the placebo. When adjusted for the presence of dementia, cardiovascular events, and subsequent strokes, the relative risk in the treatment versus placebo group was 0.20 (95% CI, 0.08-0.5), with a number needed to treat to prevent one event of 14.
The authors also tracked several factors known to be associated with fracture risk. Despite evidence that vitamin B12 is thought to be important in maintenance of bone mineral density (BMD), there appeared to be no difference in BMD between the treatment and control groups in this study. There was, however, a 38% drop in plasma homocysteine levels among patients taking folate and vitamin B12, compared with an increase of 31% in the placebo group. It is to this effect which the authors attribute the dramatic reduction in the incidence of hip fractures observed in the treatment group.
More evidence required
The authors of the study warn against generalizing their results to other patient populations, however. They note that the power of the study was compromised due to the small number of recorded fractures, and that, since it was conducted at a single site, the effect of folate and vitamin B12 may not be as dramatic in non-Japanese or among those with different diets or baseline vitamin intake.
Dr. van Meurs notes that exactly how homocysteine affects bone remains unclear. "Homocysteine could make bone more fragile by interfering with collagen cross-linking, a process that is necessary to produce strong bone," adding that "lowering homocysteine could also prevent fractures indirectly by preventing other diseases that are correlated with risk of falling and fractures."
High homocysteine has also been associated with cardiovascular disease and dementia, so any correlation with hip fracture could be complicated by the presence of these diseases, Dr. van Meurs points out. "However, the authors have adjusted for these potential confounders, and this did not affect the outcome of the study, making it a less likely explanation for the relationship between homocysteine and the risk of fracture."
References
- Sato, Y, Honda Y, Iwamoto J et al. Effect of folate and mecobalamin on hip fractures in patients with stroke. A randomized controlled trial. JAMA. 2005;293:1082-1088.
- Van Meurs JBJ, Uitterlinden A. Homocysteine and fracture prevention. JAMA. 2005; 293:1121-1122.