Prevention of Nonvertebral Fractures With Oral Vitamin D and Dose Dependency

Centre on Aging and Mobility, University of Zurich, University Hospital, Switzerland.
Archives of internal medicine (Impact Factor: 17.33). 04/2009; 169(6):551-61. DOI: 10.1001/archinternmed.2008.600
Source: PubMed


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 (> or =65 years). We included 12 double-blind randomized controlled trials (RCTs) for nonvertebral fractures (n = 42 279) and 8 RCTs for hip fractures (n = 40 886) comparing oral vitamin D, with or without calcium, with calcium or placebo. To incorporate adherence to treatment, we multiplied the dose by the percentage of adherence to estimate the mean received dose (dose x adherence) for each trial.
The pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77-0.96) for prevention of nonvertebral fractures and 0.91 (95% CI, 0.78-1.05) for the prevention of hip fractures, but with significant heterogeneity for both end points. Including all trials, antifracture efficacy increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels for both end points. Consistently, pooling trials with a higher received dose of more than 400 IU/d resolved heterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI, 0.72-0.89; n = 33 265 subjects from 9 trials) for nonvertebral fractures and 0.82 (95% CI, 0.69-0.97; n = 31 872 subjects from 5 trials) for hip fractures. The higher dose reduced nonvertebral fractures in community-dwelling individuals (-29%) and institutionalized older individuals (-15%), and its effect was 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.

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    • "Lower serum vitamin D levels have been shown to be associated with decreased bone mineral density of the total hip and hip trochanter, increased risk of hip fracture in older men and women, and reduced response to bisphosphonate treatment in postmenopausal women with osteoporosis [6] [7] [8] [9]. Conversely, though a recent meta-analysis suggests there is no clear association between vitamin D supplementation and bone mineral density in patients without vitamin D deficiency [10], vitamin D supplementation has been shown to reduce the risk of nonvertebral and hip fracture in a dose-dependent manner [11]. In accordance with these findings, it has been suggested that vitamin D may work through bone density-independent mechanisms to improve bone health [12]. "
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    ABSTRACT: Though vitamin D is important for bone health, little is known about the monitoring and management of vitamin D levels in patients with osteoporosis in clinical practice-a deficit this chart review initiative aimed to remedy. A total of 52 physicians completed profiles for 983 patients being treated for osteoporosis between November 2008 and April 2009. Information collected included demographics; fracture risk factors; availability and level of serum vitamin D measurements; and information on osteoporosis medications and calcium and vitamin D supplementation. Physicians also evaluated patients' current regimens and detailed proposed changes, if applicable. Nearly 85% of patients were prescribed calcium and vitamin D supplements. Serum 25-hydroxy vitamin D levels were available for 73% of patients. Of these patients, approximately 50% had levels less than 80 nmol/L, which contrasts with the 37% thought to have "unsatisfactory" vitamin D levels based on physician perceptions. Physicians felt 26% of patients would benefit from additional vitamin D supplementation. However, no changes to the osteoporosis regimen were suggested for 48% of patients perceived to have "unsatisfactory" vitamin D levels. The results underscore the importance of considering vitamin D status when looking to optimize bone health.
    Journal of Osteoporosis 01/2015; 2015:312952. DOI:10.1155/2015/312952
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    • "Also, in various double-blind RCTs, vitamin D supplementation increased bone density and reduced bone loss [22, 23]. In a meta-analysis summarizing the evidence of 12 double-blind RCTs involving 42279 individuals aged 65 and older, oral vitamin D supplementation reduced the risk of hip fracture by 18% and the risk of any non-vertebral fracture by 20% [5]. However, similarly to fall prevention, the benefit on fracture prevention depends on the dose of vitamin D. Fracture prevention required a received dose (treatment dose*adherence) of more than 482 IU vitamin D per day. "
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    ABSTRACT: Besides its well-known effect on bone metabolism, recent researches suggest that vitamin D may also play a role in the muscular, immune, endocrine, and central nervous systems. Double-blind RCTs support vitamin D supplementation at a dose of 800 IU per day for the prevention of falls and fractures in the senior population. Ecological, case-control and cohort studies have suggested that high vitamin D levels were associated with a reduced risk of autoimmune diseases, type 2 diabetes, cardio-vascular diseases and cancer but large clinical trials are lacking today to provide solid evidence of a vitamin D benefit beyond bone health. At last, the optimal dose, route of administration, dosing interval and duration of vitamin D supplementation at a specific target dose beyond the prevention of vitamin D deficiency need to be further investigated.
    09/2014; 72(1):32. DOI:10.1186/2049-3258-72-32
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    • "The strengths of this study are the inclusion of people with hip fracture who have similar characteristics to the Australian report of 16,518 patients with hip fracture [8] with a similar mean age (83.0 vs 83.9 years), hip fracture subtype (53% vs 51% with neck femur fractures), and mode of surgery (61.3% vs 60.1% internal fixation). The weaknesses of this study are in the under-recruitment of people with severe pre-existing disability compared to the usual population with hip fractures: (1) low number of participants from residential aged care facility; (2) participants with fewer total comorbidities; (3) a small number with preexisting cognitive impairment (16.0%), although one-sixth was actually documented in cognitive impairment in our cohort, suggesting either underreporting of the disease at recruitment, or first diagnosis of disease following a hip fracture. "
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    ABSTRACT: Background: Hypovitaminosis D is particularly common among older people with a proximal femoral (hip) fracture. There are currently no agreed strategies for vitamin D replenishment after hip fracture surgery. The REVITAHIP Study is a multisite, double-blinded randomized-controlled trial investigating the effects of an oral vitamin D loading dose on gait velocity after hip fracture surgery. We describe the baseline characteristics of participants, aiming to document hypovitaminosis D and its associations after hip fracture.
    BMC Geriatrics 09/2014; 14(1):101. DOI:10.1186/1471-2318-14-101 · 1.68 Impact Factor
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