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Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis
Abstract
BACKGROUND: Vitamin D and related compounds have been used to prevent osteoporotic fractures in older people. OBJECTIVES: To determine the effects of vitamin D or related compounds, with or without calcium, for preventing fractures in older people. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 3), MEDLINE, EMBASE, CINAHL, and reference lists of articles. Most recent search: October 2007. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing vitamin D or related compounds, alone or with calcium, against placebo, no intervention, or calcium alone, reporting fracture outcomes in older people. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, and extracted data. Data were pooled, where admissible, using the fixed-effect model, or random-effects model if heterogeneity between studies appeared high. MAIN RESULTS: Forty-five trials were included. Vitamin D alone appears unlikely to be effective in preventing hip fracture (nine trials, 24,749 participants, RR 1.15, 95% CI 0.99 to 1.33), vertebral fracture (five trials, 9138 participants, RR 0.90, 95% CI 0.42 to 1.92) or any new fracture (10 trials, 25,016 participants, RR 1.01, 95% CI 0.93 to 1.09).Vitamin D with calcium reduces hip fractures (eight trials, 46,658 participants, RR 0.84, 95% CI 0.73 to 0.96). Although subgroup analysis by residential status showed a significant reduction in hip fractures in people in institutional care, the difference between this and the community-dwelling subgroup was not significant (P = 0.15).Overall hypercalcaemia is significantly more common in people receiving vitamin D or an analogue, with or without calcium (18 trials, 11,346 participants, RR 2.35, 95% CI 1.59 to 3.47); this is especially true of calcitriol (four trials, 988 participants, RR 4.41, 95% CI 2.14 to 9.09). There is a modest increase in gastrointestinal symptoms (11 trials, 47,042 participants, RR 1.04, 95% CI 1.00 to 1.08, P = 0.04) and a small but significant increase in renal disease (11 trials, 46,537 participants, RR 1.16, 95% CI 1.02 to 1.33). AUTHORS' CONCLUSIONS: Frail older people confined to institutions may sustain fewer hip fractures if given vitamin D with calcium. Vitamin D alone is unlikely to prevent fracture. Overall there is a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D or its analogues. Calcitriol is associated with an increased incidence of hypercalcaemia.
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“There are insufficient data for hip fracture outcomes from trials of alphacalcidiol, 26 B 12 /folate, or vitamin K by other investigators, but vitamin K is reported to have no effect on bone density 29 or vertebral fracture risk.30”
From Systematic review and statistical analysis of the integrity of 33 randomized controlled trials (2016) · cites this paper as [26]
In the citing paper
“However, in low-income settings, the pubertal growth spurt is frequently extended, thus allowing a substantial degree of catch-up in height and weight compared with the international growth reference standards.3”
From Nutrition in adolescents: physiology, metabolism, and nutritional needs (2017) · cites this paper as [3]
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“Adolescence is a time for catch-up growth; the extent to which pubertal growth can contribute to stunting recovery at this time is under much investigation, but studies of children who migrated or were adopted may offer more insight into later linear growth increases.3,82,83”
From Nutrition in adolescents: physiology, metabolism, and nutritional needs (2017) · cites this paper as [3]
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“The necessary requirements of future frailty instruments, including the important issue of clinical sensibility, have been defined (138).”
From Frailty in elderly people (2013) · cites this paper as [138]
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Metadata
- Authors
- Avenell, A., Gillespie, W. J., Gillespie, L. D., & O'Connell, D.
- Affiliations
- University of Aberdeen (GB)
- University of Hull (GB)
- University of Otago (NZ)
- ORCID
- Avenell, Alison
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- John Wiley & Sons, Ltd
- Published
- 2009-04-15
- Issue
- 2
- Pages
- CD000227-CD000227
- ISSN
- 1361-6137 (ISSN-L)
- OpenAlex
- W1564323166
- Cited by
- 667
- References
- 205
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 9 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 14 · 2018: 9 · 2017: 20 · 2016: 32 · 2015: 42 · 2014: 56 · 2013: 57 · 2012: 54
- Type
- reference entry
- Language
- en
- Update notices
- new_version (2014-04-14)
- Open access
- closed
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin K Research Studies
- Keywords
- vitamin D, vitamin D analogs, osteoporosis, postmenopausal osteoporosis, involutional osteoporosis, fracture prevention, hip fracture, vertebral fractures, calcium supplementation, hypercalcemia, 1,25-dihydroxyvitamin D3, community-dwelling older adults, fall prevention, falls in older adults
- MeSH terms
- Aged, Calcitriol, Female, Humans, Hydroxycholecalciferols, Male, Osteoporosis, Vitamin D, Vitamins, Osteoporosis, Postmenopausal, Randomized Controlled Trials as Topic, Frail Elderly, Dietary Supplements, Bone Density Conservation Agents, Fractures, Bone
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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