Vitamine D tegen botbreuken*
Uit een analyse van 20 studies onder ruim 80.000 deelnemers van 65 jaar en ouder blijkt dat voldoende vitamine D belangrijk is in het voorkomen van botbreuken. De afname van het aantal botbreuken is duidelijk afhankelijk van de hoeveelheid vitamine D die per dag ingenomen wordt en hoe lang de inname al duurt en is onafhankelijk van de hoeveelheid calcium die ingenomen wordt. Dagelijkse inname van 10 mcg
vitamine D had geen enkel effect. Hogere dosering en liefst voor jaren deed de kans op een botbreuk flink verminderen.
Nonvertebral Fracture Prevention With Vitamin D May Be Dose-Dependent
Prevention of nonvertebral fractures with vitamin D is dose-dependent for individuals aged 65 years or older, according to the results of a meta-analysis of randomized controlled trials (RCTs) reported in the Archives of Internal Medicine.
"A dose-response relationship between vitamin D and fracture reduction is supported by epidemiologic data showing a significant positive trend between serum 25-hydroxyvitamin D concentrations and hip bone density and lower extremity strength," write Heike A. Bischoff-Ferrari, DrPH, from University of Zurich, University Hospital in Switzerland, and colleagues. "Antifracture efficacy with supplemental vitamin D has been questioned by recent trials. We performed a meta-analysis on the efficacy of oral supplemental vitamin D in preventing nonvertebral and hip fractures among older individuals (≥65 years)."
The reviewers identified 12 double-blind RCTs for nonvertebral fractures, enrolling a total of 42,279 subjects, and 8 RCTs for hip fractures, enrolling a total of 40,886 subjects, which compared the effects of oral vitamin D, with or without calcium, with those of calcium alone or of placebo. As a measure of treatment adherence, the reviewers calculated the mean received dose for each trial by multiplying the dose by the percentage of adherence.
There was significant heterogeneity for both end points. For prevention of nonvertebral fractures, the pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77 – 0.96), and RR was 0.91 (95% CI, 0.78 – 1.05) for the prevention of hip fractures. When all trials were included, antifracture efficacy for both endpoints increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels.
Pooling trials with a higher received dose of more than 400 U/day consistently resolved heterogeneity, with pooled RR for nonvertebral fractures being 0.80 (95% CI, 0.72 – 0.89; 9 trials enrolling 33,265 subjects), and pooled RR for hip fractures being 0.82 (95% CI, 0.69 – 0.97; 5 trials enrolling 31,872 subjects).
In community-dwelling individuals, the higher dose was associated with a 29% decrease in nonvertebral fractures vs a 15% decrease seen in institutionalized individuals. These effects were independent of additional calcium supplementation.
"Nonvertebral fracture prevention with vitamin D is dose dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.
"A higher received dose of supplemental vitamin D (482-770 IU/d) should reduce nonvertebral fractures by at least 20% and hip fractures by at least 18%," the study authors write. "Our results do not support use of low-dose vitamin D with or without calcium in the prevention of fractures among older individuals."
Limitations of this meta-analysis include those inherent in the reviewed studies and the small number of studies for 1-alpha-hydroxylated vitamin D.
"The greater fracture reduction with a higher received dose or higher achieved 25-hydroxyvitamin D levels for both any nonvertebral fractures and hip fractures suggests that higher doses of vitamin D should be explored in future research to optimize antifracture efficacy," the review authors conclude. "Also, it is possible that greater benefits may be achieved with earlier initiation of vitamin D supplementation and longer duration of use."
The Swiss National Foundation and the Robert Bosch Foundation supported this study. The authors have disclosed no relevant financial relationships.
Arch Intern Med. 2009;169:551–561.
Clinical Context
According to the current authors, the antifracture benefit of vitamin D has been questioned, and a 2007 meta-analysis concluded that vitamin D may only reduce fracture risk in combination with calcium, but recent studies have suggested a positive correlation between 25-hydroxyvitamin D concentrations and hip bone density and lower extremity strength.
This is a systematic review and meta-analysis of double-blind RCTs to examine the effect of vitamin D on fracture risk in older adults.
Study Highlights
· MEDLINE, the Cochrane Controlled Trials Register, and the EMBASE databases were searched to 2008 for RCTs that included vitamin D supplementation with cholecalciferol or ergocalciferol with a minimum follow-up of 1 year and more than a total of 1 fracture, with mean age of 65 years or higher and adherence data.
· Excluded were uncontrolled or observational studies and those taking place after organ transplantation or stroke or in patients who received corticosteroids or had unstable medical conditions.
· The primary outcome was RR for first or repeated nonvertebral or hip fracture in those receiving vitamin D supplementation with or without calcium.
· Those who had 25-hydroxyvitamin D levels measured were also analyzed.
· 12 RCTs were included, 8 of which included hip fractures.
· The 12 trials included 42,279 subjects with a mean age of 78 years, of whom 89% were women.
· In 3 trials, the received dose of vitamin D was less than 400 U/day, and in 9 RCTs the dose was 482 to 770 U/day, with 500 to 1200 mg/day of calcium supplements given.
· In the 12 high-quality studies, the pooled RR for any nonvertebral fracture was 0.86, but there was significant heterogeneity among studies.
· For the 9 trials with a higher received dose of more than 400 U/day of vitamin D (482 – 770 U/day, 33,265 individuals) the pooled RR was 0.80 for a 20% risk reduction with little heterogeneity.
· The number needed to treat (NNT) for 12 to 84 months of treatment with vitamin D to prevent a nonvertebral fracture was 93.
· The pooled RR for nonvertebral fractures was lower for ergocalciferol at 10% compared with 23% for cholecalciferol.
· The reduced risk for higher-dose vitamin D was significant among subgroups including community-dwelling subjects and younger persons.
· In the 8 high-quality trials that included hip fractures, the pooled RR for any dose of vitamin D was 0.91, with significant heterogeneity between studies.
· For the 5 trials with a received dose of more than 400 U/day (482 – 770 U/day, 31,872 individuals), the pooled RR was 0.82, with little heterogeneity.
· The higher dose of vitamin D reduced hip fracture risk by 18%, with an NNT of 168 for 12 to 84 months of use.
· The same effect was seen for those with higher 25-hydroxyvitamin D levels.
· The addition of calcium did not further improve the antifracture efficacy of vitamin D.
· In subanalysis, doses of vitamin D below 400 U daily did not reduce fracture risk.
· The higher dose reduced nonvertebral fracture risk by 29% in community-dwelling older adults and by 15% in institutionalized older adults.
· The authors concluded that vitamin D supplementation in doses above 400 U/day was associated with significantly reduced risk for nonvertebral fracture by 20% and hip fracture by 18%.
· There was a likelihood that cholecalciferol was more effective than ergocalciferol.
Pearls for Practice
· Use of vitamin D is associated with reduced risk for nonvertebral and hip fractures in older adults independent of calcium supplementation.
· The dose of vitamin D for fracture prevention should be higher than 400 U daily; this dose is effective in both community-dwelling and institutionalized older
adults. (Mei
2009)
