Research Articles - Bone Nutrition
Effect of Folate and Mecobalamin on Hip Fractures in Patients with Stroke:
A Randomized Controlled Trial
Elevated levels of homocysteine are a risk factor for ischemic stroke and osteoporotic fractures in older men and women. A recent epidemiological study found that high blood levels of homocysteine were associated with an increased risk of nonvertebral fractures in older people independent of bone mineral density or recent falls. These researchers theorized that supplementation with folate (as folic acid) and vitamin B12 may reduce blood homocysteine levels and thus the incidence of hip fractures in patients with hemiplegia (paralysis of one side of the body) following stroke. In a double-blind, randomized controlled study, 628 elderly Japanese, aged 65 years or older, with residual hemiplegia for at least 1 year received either 5 mg of folate and 1,500 μg of vitamin B12, or a placebo for 2 years. Both groups had high baseline levels of plasma homocysteine and low serum levels of cobalamin and folate. After 2 years, homocysteine levels decreased 38 percent in the treatment group and increased 31 percent in the placebo group. The number of hip fractures per 1,000 patient-years was 10 and 43 for the treatment and placebo groups, respectively. The adjusted relative risk, absolute risk reduction, and number needed to treat for hip fractures in the treatment vs. placebo groups were 0.20 percent, 7.1 percent, and 14 respectively. No adverse effects were reported in the paper. In elderly individuals with a high baseline fracture risk, combined treatment with folate and vitamin B12 was safe and effective in reducing the risk of a hip fracture following stroke. It has been theorized that vitamin B12 improves bone quality by increasing osteocalcin concentration (a major protein in bone that binds with calcium) and by promoting collagen cross-linking. Additional research is needed to validate these findings in other population groups.
Funding: Source not identified.
Y Sato, Y Honda, J Iwamoto, T Kanoko, and K Satoh. Journal of the American Medical Association (JAMA) 2005 293:1082-1088.
Fracture Prevention with Vitamin Randomized Controlled Trials
Calcium together with vitamin D is thought to be effective in the prevention of hip and nonvertebral fractures among the aged. This study estimated the effectiveness of vitamin D in preventing such fractures in older persons through a systematic evaluation of published studies. Randomized controlled trials of supplemental vitamin D with or without calcium, calcium alone, or placebo in participants 60 years and over, with at least one fracture, and follow-up of at least one year were pooled and analyzed using meta-analysis techniques. Individual studies were assessed for adequacy of the randomization procedure, treatment concealment and blinding,
and withdrawals. Five trials for hip fracture (n=9,294) and 7 trials for nonvertebral fracture risk (n=9,820) met the inclusion criteria. Vitamin D supplementation ranged from 400 to 800 IU/day of cholecalciferol, the active form of vitamin D3. Calcium intake, from a variety of calcium salts, ranged from 500 to 1,200 mg/day. The higher- dose vitamin D (700-800 IU/day) combined with calcium (500 to 1,200 mg/day) reduced the risk for hip fractures by 26 percent and all nonvertebral fractures by
23 percent. The lower-dose vitamin D (400 IU/day) was not sufficient to prevent fractures. The additional effect of calcium and independent effect of higher-dose vitamin D could not be examined, as the higher-dose vitamin D studies (except for one) provided calcium supplements and the lower-dose studies did not. Future studies should focus on independent and interactive effects of higher doses of vitamin D and calcium in the prevention of primary and secondary fractures.
Funding: Medial Foundation and the James Knox Memorial Foundation.
HA Bischoff-Ferrari, WC Willett, JB Wong, E Giovannucci, T Dietrich, and B Dawson-Hughes. Journal of the American Medical Association (JAMA) 2005 293:2257- 2264.
Oral Vitamin D3 and Calcium for Secondary Prevention of Low-trauma Fractures in Elderly People:
A Randomised Placebo-controlled Trial
Vitamin D and calcium are often recommended for prevention of fractures. Elderly people who have experienced a fracture are at higher risk of another. In this study, the effect of supplemental vitamin D3 and calcium, taken alone or together on the prevention of secondary fractures, was examined. In a factorial-design trial, 5,292 people aged 70 years or older (85 percent female) who had suffered a low-trauma osteoporotic fracture within the past 10 years were randomly assigned to receive either 800 IU vitamin D3, 1,000 mg calcium (given as calcium carbonate), vitamin D3 combined with calcium, or a placebo. The individuals were followed up for between 24 and 62 months. The primary outcome was the development of new low-trauma fractures, confirmed by radiography. Thirteen percent of the participants had a new low-trauma fracture, 26 percent of which were of the hip. The groups did not differ in the incidence of all-new fractures, hip fractures, deaths, number of falls, or quality of life. By 24 months, 54·5 percent of the individuals in the study were still taking the supplements and 35·8 percent had stopped taking the supplements but were still providing data for the main outcomes of the study. Of the remaining participants, 8·5 percent had died and 1·1 percent withdrew from the study. This study failed to support previous observations of a benefit of calcium or vitamin D supplementation for the prevention of fractures. The poor compliance rates raise questions about the generalizability of the findings. More studies in elderly people are needed to confirm any benefits from supplemental vitamin D on falls and fracture endpoints.
Funding: Scottish Executive Health Department.
The RECORD Trial Group. Lancet (Lancet) 2005 365:1621-1628.
Long-term Calcium Supplementation Does not Affect the Iron Status of 12-14 year-old Girls
Nutrient requirements for iron and calcium are higher in adolescent girls around the time of menarche. Calcium supplementation can compromise long-term iron status, but few data are available for adolescent girls. The aim of this randomized, double- blind, placebo controlled study was to evaluate whether calcium supplementation affected iron status in 113 Dutch girls aged 12-14 years. Subjects took 500 mg calcium (as calcium carbonate) a day or a placebo with the main daily meal for 1 year. Measures of iron status (concentrations of hemoglobin, serum ferritin, and serum transferrin receptors) were collected at baseline and one year along with dietary calcium intake through a food frequency questionnaire. The mean hemoglobin
level at baseline was 134 grams/liter. Two groups were selected according to their dietary calcium intake: a medium intake group (1,000-1,304 mg/day; n=60) and a low intake group (<713 mg/day; n=53). Calcium supplementation had no effect on iron status in either group. This study shows that calcium supplementation does not alter iron status in iron-sufficient adolescent girls. Additional research is necessary to understand the effect of long-term calcium supplementation on iron status in iron- deficient adolescents.
Funding: Danish government Food and Technology Research Program and Danish Dairy Research Foundation.
Picking a Bone with Vitamin A: High Levels, Weak Bones Linked
A study published in January 2003 in the New England Journal of Medicine linked high levels of vitamin A to bone fractures, echoing findings of two other studies published in the last year.
While this study is not considered conclusive in linking high intake of vitamin A to increased risk of osteoporosis, the developing body of research is leading some experts to advise consumers to be more vigilant about abiding by federal intake guidelines for vitamin A and the degree to which foods fortified with it can increase risk of poor bone health.
In an editorial published with the study, Paul Lips of Vrije Universiteit in Amsterdam wrote that "vitamin A supplementation and fortification of food with vitamin A may be harmful" in well- fed populations where osteoporosis is growing. Note: The problem appears to be vitamin A oxidation that occurs during manufacture, storage, or processing rather than native vitamin A since only oxidized vitamin A has been linked to problems when carefully examined in other studies. This is supported by the fact that beta carotene is not associated with any risk. The body converts beta carotene to active vitamin A (retinol) in the liver as needed.
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