RESEARCH - Folate and B12 cut osteoporotic fracture risk

March 10, 2005

Folate and B12 cut osteoporotic fracture risk

Rheumawire

Mar 3, 2005

Janis

Tagawa, Japan - Stroke more than doubles the risk of subsequent hip

fracture, and high levels of plasma homocysteine are associated stroke and

with hip-fracture risk. Dr Yoshiro Sato (Mitate Hospital, Tagawa, Japan)

reports in the March 2, 2005 issue of the Journal of the American Medical

Association that daily folic acid and vitamin B12 (mecobalamin) supplements

dramatically reduced the incidence of hip fracture in a double-blind,

randomized, controlled study of 628 stroke patients [1].

Dr Joyce BJ van Meurs (Erasmus Medical Center, Rotterdam, the Netherlands),

who contributed an accompanying editorial [2], tells rheumawire, " The study

shows a clear difference in fracture incidence between patients who receive

folate/mecobalamin treatment and placebo. 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. "

Supplements reduce homocysteine levels, may improve bone quality

Patients in the Sato study had residual hemiplegia for at least 1 year

following a first ischemic stroke. They were randomized to daily oral

treatment with 5 mg of folic acid and 1500 g of mecobalamin or to double

placebo. Follow-up time was 2 years, and 559 patients completed the study.

There were no significant adverse effects.

The number of hip fractures per 1000 patient-years was 10 for the treatment

group vs 43 for the placebo group (p<0.001). The adjusted relative risk in

the treatment vs placebo groups was 0.20 (95% CI 0.088-0.50).

" [G]iven the relatively low power of this study, it is important to

emphasize that the true relative risk reduction may be as low as 0.5 (the

lower end of the confidence interval), " Sato writes.

The number needed to treat (NNT) to prevent a single hip fracture was 14. By

comparison, Sato points out that, in other studies, the NNT was 15 for

alendronate (Fosamax, Merck) and for raloxifene (Evista, Lilly).

The decrease in hip fractures was not due to an effect on bone-mineral

density (BMD), which decreased in both groups by about the same amount over

the 2-year period. The number of falls in the 2 groups was also similar.

Sato points out that these findings should be viewed with some caution,

because this was a particularly high-risk population. Loss of BMD in the

femoral neck was 2.9% to 3.0% in these subjects but would be expected to be

less than 1% in untreated, community-dwelling, elderly subjects who had not

had strokes. Similarly, the incidence of hip fracture in the placebo group

in this trial was 8.6% in 2 years, compared with an incidence of 1.75% to

4.65% per year in other studies of stroke patients. Sato suggests that this

might be due to the low intake of vitamin D and calcium in the traditional

Japanese diet.

Elevated homocysteine levels are a risk factor for osteoporotic fracture,

and plasma homocysteine levels dropped by 38% in the treatment group and

increased by 31% in the placebo group over the 2 years of the study

(p<0.001).

Sato suggests that the lack of association with BMD may mean that the

fracture prevention was due to the reduced homocysteine levels and

consequent reduced interference with collagen cross-linking and formation of

collagen fibrils. These structures are important for collagen network

strength, and, by impeding their formation, homocysteine might alter the

bone matrix and weaken the bone. However, Sato warns that there are

currently no data on bone turnover or on bone collagen cross-links in

patients with high plasma homocysteine.

" The fact that BMD seems not to explain the relationship between

homocysteine and fracture makes homocysteine a potentially valuable (and

modifiable) risk factor for fracture, " van Meurs says. " This suggests that

homocysteine has an effect on the quality of bone rather than its quantity

(BMD). "

Sources

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 AG. Homocysteine and fracture

prevention. JAMA 2005; 293:1121-1122.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

March 10, 2005

Very interesting . I wanted to read more about homocysteine and

found this article:

http://www.quackwatch.org/03HealthPromotion/homocysteine.html

It makes me wonder if we all should have our homocysteine levels

checked, especially if anemia is a problem.

a

On Thu, 10 Mar 2005 07:39:23 -0600, <Matsumura_Clan@...> wrote:

> Folate and B12 cut osteoporotic fracture risk

>

> Rheumawire

> Mar 3, 2005

> Janis

>

> Tagawa, Japan - Stroke more than doubles the risk of subsequent hip

> fracture, and high levels of plasma homocysteine are associated stroke and

> with hip-fracture risk. Dr Yoshiro Sato (Mitate Hospital, Tagawa, Japan)

> reports in the March 2, 2005 issue of the Journal of the American Medical

> Association that daily folic acid and vitamin B12 (mecobalamin) supplements

> dramatically reduced the incidence of hip fracture in a double-blind,

> randomized, controlled study of 628 stroke patients [1].

>

> Dr Joyce BJ van Meurs (Erasmus Medical Center, Rotterdam, the Netherlands),

> who contributed an accompanying editorial [2], tells rheumawire, " The study

> shows a clear difference in fracture incidence between patients who receive

> folate/mecobalamin treatment and placebo. 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. "

>

> Supplements reduce homocysteine levels, may improve bone quality

> Patients in the Sato study had residual hemiplegia for at least 1 year

> following a first ischemic stroke. They were randomized to daily oral

> treatment with 5 mg of folic acid and 1500 g of mecobalamin or to double

> placebo. Follow-up time was 2 years, and 559 patients completed the study.

> There were no significant adverse effects.

>

> The number of hip fractures per 1000 patient-years was 10 for the treatment

> group vs 43 for the placebo group (p<0.001). The adjusted relative risk in

> the treatment vs placebo groups was 0.20 (95% CI 0.088-0.50).

>

> " [G]iven the relatively low power of this study, it is important to

> emphasize that the true relative risk reduction may be as low as 0.5 (the

> lower end of the confidence interval), " Sato writes.

>

> The number needed to treat (NNT) to prevent a single hip fracture was 14.

> By

> comparison, Sato points out that, in other studies, the NNT was 15 for

> alendronate (Fosamax, Merck) and for raloxifene (Evista, Lilly).

>

> The decrease in hip fractures was not due to an effect on bone-mineral

> density (BMD), which decreased in both groups by about the same amount over

> the 2-year period. The number of falls in the 2 groups was also similar.

>

> Sato points out that these findings should be viewed with some caution,

> because this was a particularly high-risk population. Loss of BMD in the

> femoral neck was 2.9% to 3.0% in these subjects but would be expected to be

> less than 1% in untreated, community-dwelling, elderly subjects who had not

> had strokes. Similarly, the incidence of hip fracture in the placebo group

> in this trial was 8.6% in 2 years, compared with an incidence of 1.75% to

> 4.65% per year in other studies of stroke patients. Sato suggests that this

> might be due to the low intake of vitamin D and calcium in the traditional

> Japanese diet.

>

> Elevated homocysteine levels are a risk factor for osteoporotic fracture,

> and plasma homocysteine levels dropped by 38% in the treatment group and

> increased by 31% in the placebo group over the 2 years of the study

> (p<0.001).

>

> Sato suggests that the lack of association with BMD may mean that the

> fracture prevention was due to the reduced homocysteine levels and

> consequent reduced interference with collagen cross-linking and formation

> of

> collagen fibrils. These structures are important for collagen network

> strength, and, by impeding their formation, homocysteine might alter the

> bone matrix and weaken the bone. However, Sato warns that there are

> currently no data on bone turnover or on bone collagen cross-links in

> patients with high plasma homocysteine.

>

> " The fact that BMD seems not to explain the relationship between

> homocysteine and fracture makes homocysteine a potentially valuable (and

> modifiable) risk factor for fracture, " van Meurs says. " This suggests that

> homocysteine has an effect on the quality of bone rather than its quantity

> (BMD). "

>

> Sources

>

> 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 AG. Homocysteine and fracture

> prevention. JAMA 2005; 293:1121-1122.

>

> Not an MD

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

>

March 10, 2005