Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis

Reid, Ian R.; Bolland, Mark J; Grey, Andrew

doi:10.1016/s0140-6736(13)61647-5

Cited by 551 publications

(383 citation statements)

References 51 publications

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“…13,14 More recently, Reid et al have published a systematic review which provides very little evidence of an overall benefit of vitamin D supplementation on bone density 15 and Balland et al confirmed that vitamin D supplementation with or without calcium does not reduce skeletal or non-skeletal outcomes in unselected communitydwelling individuals by more than 15%. 16 To date, the evidence is not yet sufficient to recommend vitamin D3 supplementation for subjects with vitamin D insufficiency (defined as 30-50 nmol/L 25(OH)D) however it helps to understand that subjects with vitamin D deficiency (<30 nmol/L 25(OH)D) could profit from vitamin D3 supplementation by maintaining bone health and reduction in fracture risk.…”

Section: Vitamin D and Bone Fracturesmentioning

confidence: 99%

“…It is known that vitamin D has a wide range of biological actions (Table 2), [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] and that vitamin D receptor is present in most tissues and cells in the body. 26 As a result, it is not unexpected that multiple studies 27 have associated vitamin D deficiency with cardiovascular diseases, type 2 diabetes, hypertension, many types of cancer, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, and infectious diseases.…”

Section: Vitamin D and Extraskeletal Diseasesmentioning

confidence: 99%

“…28 An important prospective study with a large sample of patients revealed that 25(OH)D <15 ng/mL compared to 25(OH)D >30 ng/mL was associated with highly significant increases in the prevalence Bone Conflicting data about vitamin D supplementation effects on bone fracture risk [11][12][13][14] Vitamin D supplementation has little effect on BMD 15,16 Cardiometabolic Low vitamin D is associated with hypertension, hyperlipidemia, peripheral vascular disease, coronary artery disease, heart failure, and stroke 17 Vitamin D supplementation reduces the incidence of diabetes 18 Central nervous system Hypovitaminosis D is predictor for dementia 19 No significant associations between lower levels of 25(OH)D and lower cognitive test scores…”

Section: Cardiovascular Effectsmentioning

confidence: 99%

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Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

Montagnani

Nardi²,

Cercignani

et al. 2015

Ital J Med

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Vitamin D and calcium are essential for bone health. An adequate calcium-phosphorus product determines a high quality mineralization long lifetime. In older people, both calcium and vitamin D levels may be lower causing osteomalacia and/or osteoporosis with a higher risk of fracture. Epidemiological data have clearly associated serum vitamin D lower levels (deficiency) with bone fracture in older people, however, not univocal data exist in regard to a beneficial effect of vitamin D supplementation in general population. Although not systematic, the present review aims to make a narrative synthesis of the most recent published data on vitamin D effect not only on bone, classical target associated with vitamin D studies, but namely on extraskeletal diseases. In fact, recently, there has been an increasing interest on this latter issue with surprising findings. Vitamin D, and in particular its deficiency, seems to have a role in pathophysiological pathways in several diseases involving cardiovascular, central nervous system and neoplastic process. On the other hand, vitamin D supplementation may modify the outcome of a wide range of illnesses. Up to date the data are conflicting mainly because of difficulty to establish a consensus on the threshold of vitamin D deficit. The US Institute of Medicine recommends to distinguish a level of insufficiency [defined as 30-50 nmol/L or 16-25 ng/mL of 25(OH)D] and another of deficiency identified by 25(OH)D levels lower than 30 nmol/L (or <16 ng/mL). This latter level is considered a minimum level necessary in older adults to minimize the risk of falls, fracture and probably to have some effects of vitamin D supplementation in extraskeletal diseases. Although there are no absolute certainties in such issue, the most recent data suggest that vitamin D deficiency, and its supplementation, may play an important role in a wide range of diseases other than in bone metabolic diseases in older but not in general population. For such reason a widespread measurement of vitamin D levels in general population, and not only in older, seems to be inappropriate and it could induce an overuse of vitamin D supplementation in situations in which its efficacy and cost-effectiveness have not been proven.

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Section: Vitamin D and Bone Fracturesmentioning

confidence: 99%

Section: Vitamin D and Extraskeletal Diseasesmentioning

confidence: 99%

Section: Cardiovascular Effectsmentioning

confidence: 99%

See 1 more Smart Citation

Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

Montagnani

Nardi²,

Cercignani

et al. 2015

Ital J Med

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“…However there remains considerable controversy over the relationship between low vitamin D status and risk of hi p and other osteoporotic fractures. Hence, the clinical utility of vitamin D (25(OH)D) meas urement as a risk marker for fracture is unresolved [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…Meta-analyses indicate that vitamin D in combination with calcium may reduce fracture risk, but the number of randomized controlled trials are few and with diverging results [10][11][12][13]. Possible benefits have been seen primarily in the elderly but not in the general population [4], which may be in line with the reduced ability to activate vitamin D from skin exposure and reduced exposure and nutritional intake among the elderly and very elderly [14]. The findings are similar in a systematic re vi ew whe re, de spite lower serum 25(OH)D in hip fracture patients, neither high nor low doses of supplementation influence d hip fracture risk [15].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D insufficiency over 5 years is associated with increased fracture risk—an observational cohort study of elderly women

et al. 2014

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Link to publication Citation for published version (APA): Buchebner, D., McGuigan, F., Gerdhem, P., Malm, J., Ridderstråle, M., & Åkesson, K. (2014). Vitamin D insufficiency over 5 years is associated with increased fracture risk-an observational cohort study of elderly women. Osteoporosis International, 25(12), 2767-2775. DOI: 10.1007/s00198-014-2823 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ABSTRACTPurpose: Vitamin D insufficiency among the elderly is common, however relatively little is known about the effects of long-term hypovitaminosis D on fracture. We investigated sequential assessment of serum 25(OH)D at age 75 and 80 to determine if continuously low 25(OH)D levels are associated with incre ased 10-year fracture incidence.Methods: 1044 Swedish women from the population based OPRA cohort, all 75 years old, attended at baseline (BL); 715 attended at 5 years. S-25(OH)D was available in 987 and 640 respectively and categorized as: <50 (Low); 50-75 (Intermediate); >75 nmol/L (High). Incident fracture data was coll e cte d with maximum follow-up to 90 years of age.Results: Hip fracture incidence between age 80-85 was higher in women who had low 25(OH)D at both baseline and 5y (22.2% (Low) vs 6.6% (High); p=0.003). Between age 80-90 hip fracture incidence was more than double that of women in the high category (27.9% vs 12.3%; p=0.006). Within 5-years 50% of women in the continuously low group compared to 34% in the continuously high 25(OH)D group had an osteoporotic fracture (p=0.004) while 10-year incidence was higher compared to the intermediate (p=0.020) but not the high category (p=0.053). The 10-year relative risk of hip fracture was almost 3 times higher and osteoporotic fracture risk almost doubled for women in the lowest 25(OH)D category compared to the high category (HR 2.7 and 1.7; p=0.003 and 0.023 respectively). Conclusion:In these elderly women, 25(OH)D insufficiency over 5-years was associate d wi th i ncre ase d 10-year risk of hip and major osteoporotic fractures.

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Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength

Burt

Billington

Rose

et al. 2019

JAMA

254

291

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IMPORTANCE Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day.OBJECTIVE To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength.DESIGN, SETTING, AND PARTICIPANTS Three-year, double-blind, randomized clinical trial conducted in a single center in Calgary, Canada, from August 2013 to December 2017, including 311 community-dwelling healthy adults without osteoporosis, aged 55 to 70 years, with baseline levels of 25-hydroxyvitamin D (25[OH]D) of 30 to 125 nmol/L. INTERVENTIONS Daily doses of vitamin D 3 for 3 years at 400 IU (n = 109), 4000 IU (n = 100), or 10 000 IU (n = 102). Calcium supplementation was provided to participants with dietary intake of less than 1200 mg per day. MAIN OUTCOMES AND MEASURESCo-primary outcomes were total volumetric BMD at radius and tibia, assessed with high resolution peripheral quantitative computed tomography, and bone strength (failure load) at radius and tibia estimated by finite element analysis. RESULTSOf 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (−3.9 mg HA/cm 3 [95% CI, −6.5 to −1.3]) and 10 000 IU group (−7.5 mg HA/cm 3 [95% CI, −10.1 to −5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of −1.2% (400 IU group), −2.4% (4000 IU group), and −3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were −1.8 mg HA/cm 3 (95% CI, −3.7 to 0.1) in the 4000 IU group and −4.1 mg HA/cm 3 in the 10 000 IU group (95% CI, −6.0 to −2.2), with mean percent change values of −0.4% (400 IU), −1.0% (4000 IU), and −1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12).CONCLUSIONS AND RELEVANCE Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful.

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Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis

Cited by 551 publications

References 51 publications

Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

Vitamin D insufficiency over 5 years is associated with increased fracture risk—an observational cohort study of elderly women

Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength

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