Fracture prevention with vitamin D supplementation: Considering the inconsistent results

Department of General Internal Medicine and Geriatrics, University Medical Centre Groningen, RB Groningen, The Netherlands.
BMC Musculoskeletal Disorders (Impact Factor: 1.72). 03/2007; 8(1):26. DOI: 10.1186/1471-2474-8-26
Source: PubMed


A meta-analysis found that high dose vitamin D, different from low dose, decreased fracture risk by 23% for any nonvertebral fracture and by 26% for hip fracture. Unfortunately, however, this effect was not confirmed by recent trials. The aim of this paper is to explore if this inconsistency can be attributed to publication bias or heterogeneity of the trials.
The meta-analysis was extended with recent randomised controlled trials (RCTs) that were identified by a systematic review. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from raw data. A funnel plot was used to explore the possibility of publication bias. Forest plots were used to investigate if vitamin D dose, concurrent use of calcium and target population were sources of heterogeneity. Linear regression analysis of log RR on adherence rate and achieved vitamin D level was used to study whether these variables were associated with fracture risk.
A total of eleven trials was included: seven RCTs from the meta-analysis and four recently published. For any nonvertebral fracture, the funnel plot was asymmetrical because two small RCTs showed a large positive effect. This was not found for hip fracture. As reported in the meta-analysis, low dose vitamin D (<400 IU daily) was not effective. In contrast to the meta-analysis, however, the effect of high dose vitamin D (> or =700 IU daily) seemed to be dependent on target population. For any nonvertebral fracture, the pooled RR was 0.80 (95% CI, 0.70-0.90) in institutionalised persons, and 0.88 (95% CI, 0.75-1.04) in the general population; for hip fracture, pooled RR 0.72 (95% CI, 0.59 to 0.88) and 1.04 (95% CI, 0.72-1.50), respectively. Other sources of heterogeneity were not clearly found. In the meta-analysis, pooled RRs were mainly based on small trials that showed a large effect or trials in institutionalised persons.
It is likely that the inconsistency between the meta-analysis and the recent trials is, at least partially, due to publication bias and differences in target population. High dose vitamin D may be effective in institutionalised persons but probably is not effective in the general population.

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Available from: Gerbrand Izaks, May 06, 2014
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    • "Despite meta-analyses [34–37] suggesting benefit in treating the elderly and residential care patients with vitamin D, the evidence for this is limited to specific situations. There is heterogeneity of studies of vitamin D to treat osteoporosis, and findings from these meta-analyses may not be applicable to all the elderly [38], Positive results from trials with younger populations [39, 40] have been included in past meta-analyses, but these may not reflect the residential populations or the community groups included in this review. "
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    ABSTRACT: Introduction. Vitamin D is common treatment for osteoporosis. Both age >70 years and living in residential care are associated with increased fracture risk. Community dwelling elderly are a heterogeneous group who may have more similatiry with residential care groups than younger community dwelling counterparts. Aims. To review the evidence for cholecalciferol or ergocalciferol tretment of osteoporosis in either community dwelling patients aged ≥70 years of age, or redidential care patients. Secondly endpoints were changes in bone mineral denisty, and in bone turnover markers. Methods. We performed a literature search using search terms for osteoporosis and vitamin D. Treatment for at least one year was required. Results. Only one residential care study using cholecalciferol, showed non-vertebral and hip fracture reduction in vitamin D deficient subjects. In the community setting one quasi randomised study using ergocalciferol showed reduction in total but not hip or non-vertebral fracture, and a second randomised study showed increased hip fracture risk. Three studies reported increases in hip bone mineral denisty. Discussion. A minority of studies demonstrated a fracture benefit form vitamin D and one suggested possible harm in a community setting. Current practice should be to only offer this treatment to subjects identified as deficient.
    Full-text · Article · Aug 2013
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    • "Vitamin D deficiency does not only cause weaker bones due to osteomalacia, but also severe myopathy with loss of muscle strength, selective loss of the rapid type-2 fibres, dyscoordination and consequently increased propensity for falls [41]. It is therefore not surprising that meta-analyses indicate that correction of vitamin D deficiency results in a decreased fall and fracture risk [42, 43], but the effects depend on the dose of vitamin D and the target population [44]. It is still a matter of debate which doses of vitamin D3 or D2 supplementation are necessary/optimal, taking into account baseline vitamin D status and the desired serum levels to be achieved by supplementation [31–33]. "
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    ABSTRACT: The majority of osteoporotic fractures happen in individuals with BMD t-scores in the osteopenic range (-2,5< t-score <-1). However, widespread use of anti-osteoporotic medication in this group based on t-score alone is not advisable because: 1) the number needed to treat is much higher (NNT>100) than in patients with fractured and t-score below -2,5 (NNT 10-20); 2)while specific osteoporosis treatments have demonstrated significant reductions of the fracture risk in patients with t-score <-2, 5, the efficacy in patients in the osteopenic range is less well established. Therefore, an osteopenic t-score does not in itself constitute a treatment imperative. Generally, osteopenia has to be associated with either low energy fracture(s) or very high risk for future fracture as assessed with risk calculators like FRAX to warrant specific osteoporosis therapy. Vertebral fractures are now conveniently assessed using lateral x-rays from DXA machines. In the vast majority of cases antiresorptive treatments (mainly hormone replacement therapy and SERMS in younger and bisphosphonates or Denosumab in older women) are the treatments of choice in this group of patients,-only rarely is anabolic therapy indicated.
    Full-text · Article · Jun 2011 · Reviews in Endocrine and Metabolic Disorders
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    • "Vitamin D deficiency was found to be the main contributor to secondary osteoporosis in postmenopausal women with BMD osteoporosis [21], in women and men presenting with a clinical fracture and having BMD osteoporosis [22], and in patients presenting with a hip fracture [25]. Recent data indicate that vitamin D is an independent risk for fractures [26], and meta-analyses indicate that correction of vitamin D deficiency results in a decreased fall and fracture risk [27,28], but the effects depend on the dose of vitamin D and the target population [29]. Frail older people confined to institutions may sustain fewer hip fractures if given vitamin D with calcium. "
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    ABSTRACT: In the past decade, we have witnessed a revolution in osteoporosis diagnosis and therapeutics. This includes enhanced understanding of basic bone biology, recognizing the severe consequences of fractures in terms of morbidity and short-term re-fracture and mortality risk and case finding based on clinical risks, bone mineral density, new imaging approaches, and contributors to secondary osteoporosis. Medical interventions that reduce fracture risk include sufficient calcium and vitamin D together with a wide spectrum of drug therapies (with antiresorptive, anabolic, or mixed effects). Emerging therapeutic options that target molecules of bone metabolism indicate that the next decade should offer even greater promise for further improving our diagnostic and treatment approaches.
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