Need for Additional Calcium to Reduce the Risk of Hip Fracture With Vitamin D Supplementation: Evidence From a Comparative Meta-analysis of Randomized Controlled Trials

Boonen, Steven; Lips, Paul; Bouillon, Roger; Bischoff‐Ferrari, Heike A.; Vanderschueren, Dirk; Haentjens, Patrick

doi:10.1097/01.ogx.0000275405.70428.92

Cited by 46 publications

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“…While calcium supplements may decrease phosphate absorption, (35) which may augment bone resorption, (35,36,37) milk provides both calcium and phosphate. For protein, a recent meta-analysis found a small positive effect of protein supplementation on lumbar spine bone mineral density (BMD) in randomized, placebo-controlled trials but no benefit of a higher protein intake on hip fracture risk from cohort studies, (3) although recent data from the Framingham cohort study suggested a protective effect of a higher protein intake on hip fracture risk. (39) Vitamin D fortification of milk as practiced in the United States (100 IU per glass) or greater exposure to vitamin D by residence at lower latitudes may modulate the benefit of milk on hip fracture prevention.…”

Section: Discussionmentioning

confidence: 99%

“…(2) The results show that vitamin D at a received dose greater than 400 IU per day reduces the risk of any nonvertebral fracture by 20% and those at the hip by 18% independent of age, type of dwelling (community-dwelling versus nursing home), and concomitant calcium supplementation among seniors aged 65 years and older. This important dose-dependent benefit of vitamin D in nonvertebral fracture prevention was smaller in two meta-analyses published in 2007 (3,4) and one 2010 patient-based meta-analysis of 7 large trials (5) using alternative inclusion criteria that permitted opendesign trials, (3)(4)(5) use of intramuscular vitamin D, (5) and a less comprehensive (3,4) or no (5) accounting for adherence to treatment, which may result in more conservative estimates.…”

Section: Introductionmentioning

confidence: 98%

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Milk intake and risk of hip fracture in men and women: A meta-analysis of prospective cohort studies

Bischoff‐Ferrari

Dawson‐Hughes

Baron

et al. 2010

Journal of Bone and Mineral Research

123

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Milk contains calcium, phosphorus, and protein and is fortified with vitamin D in the United States. All these ingredients may improve bone health. However, the potential benefit of milk on hip fracture prevention is not well established. The objective of this study was to assess the association of milk intake with risk of hip fracture based on a meta-analysis of cohort studies in middle-aged or older men and women. Data sources for this study were English and non-English publications via Medline (Ovid, PubMed) and EMBASE search up to June 2010, experts in the field, and reference lists. The idea was to compare prospective cohort studies on the same scale so that we could calculate the relative risk (RR) of hip fracture per glass of milk intake daily (approximately 300 mg calcium per glass of milk). Pooled analyses were based on random effects models. The data were extracted by two independent observers. The results show that in women (6 studies, 195,102 women, 3574 hip fractures), there was no overall association between total milk intake and hip fracture risk (pooled RR per glass of milk per day ¼ 0.99; 95% confidence interval [CI] 0.96-1.02; Q-test p ¼ .37). In men (3 studies, 75,149 men, 195 hip fractures), the pooled RR per daily glass of milk was 0.91 (95% CI 0.81-1.01). Our conclusion is that in our meta-analysis of cohort studies, there was no overall association between milk intake and hip fracture risk in women but that more data are needed in men. ß

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Milk intake and risk of hip fracture in men and women: A meta-analysis of prospective cohort studies

Bischoff‐Ferrari

Dawson‐Hughes

Baron

et al. 2010

Journal of Bone and Mineral Research

123

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“…20 mg vitamin D reported a 16% fracture reduction, 40 and recent meta-analyses confirm the need for additional calcium with vitamin D supplementation to prevent bone loss and possibly fractures in people aged 50 years and older. 20,41,42 In conclusion, the addition of calcium and vitamin D fortified milk to the diet of postmenopausal Chinese women significantly reduced bone resorption, lowered PTH levels and improved vitamin D status within 2-8 weeks. We therefore accept our hypothesis.…”

Section: Discussionmentioning

confidence: 99%

High-calcium, vitamin D fortified milk is effective in improving bone turnover markers and vitamin D status in healthy postmenopausal Chinese women

Kruger

Todd

et al. 2012

Eur J Clin Nutr

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BACKGROUND/OBJECTIVES: Risk for developing osteoporosis increases in Asia. The purpose of the study was to evaluate the impact of a high-calcium vitamin D fortified milk (HCM) intervention on parathyroid hormone (PTH) levels, vitamin D status and markers of bone turnover in postmenopausal Chinese women. SUBJECTS/METHODS: Sixty three women (455 years) were assigned to receive two servings of either a calcium/vitamin D fortified milk or a control drink for 12 weeks. PTH, serum 25 (OH)D levels, C-telopeptide of type I collagen (CTX) levels and procollagen type I N-terminal propeptide (PINP) were measured at baseline, 2, 8 and 12 weeks of supplementation. RESULTS: Daily calcium intake at baseline ranged between 260 and 482 mg for the HCM, and 252 and 692 mg for the control group. HCM improved serum 25 (OH)D levels significantly (33.13-39.49 nmol/l), while remaining similar in the control group (29.27-28.21 nmol/l). The difference between the groups were significant at week 2, 8 and 12. The percentage change in PTH levels in the HCM group was significant from week 2 onwards compared to the control drink (Po0.017, Po0.05 and Po0.001 at weeks 2, 8 and 12, respectively). Plasma CTX of the HCM group reduced by 25% between weeks 0 and 2, remaining significantly lower and at similar levels up to week 12. The difference between the HCM and control group for PINP reached significance at weeks 8 (P ¼ 0.011) and 12 (P ¼ 0.003). CONCLUSIONS: The HCM intervention significantly improved vitamin D status and reduced bone turnover over 12 weeks in postmenopausal Chinese women.

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“…12,15 Similarly for hip fractures, the protective benefits of vitamin D versus placebo are only observed when vitamin D is combined with calcium. 39 This synergy of calcium and vitamin D is important because it is likely that estrogen's modulation and disturbance of either calcium or vitamin D-related mechanisms may attenuate the protective effects of calcium and vitamin D supplementation against colorectal cancer.…”

Section: Potential Mechanismsmentioning

confidence: 99%

Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: Reanalysis of Women's Health Initiative randomized trial

Ding

Mehta

Fawzi

et al. 2007

Intl Journal of Cancer

106

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Although calcium and vitamin-D intake were consistently shown to be inversely associated with colorectal cancer risk in several large prospective studies and protective against adenoma and cancer in multiple randomized trials, the Women's Health Initiative (WHI) of calcium and low-dose vitamin-D supplementation trial found no overall effects on colorectal cancer. However, the previous report did not recognize an important biologic interaction with estrogen therapy. We investigated the treatment interaction of estrogen with calcium and vitamin-D on risk of colorectal cancer via a reanalysis of primary data results from the WHI calcium and vitamin-D supplementation trial (1,000 mg elemental calcium, 400 IU of vitamin-D3, or placebo), reanalyzing results from women concurrently randomized to estrogen interventions and placebo. Results indicate that concurrent estrogen therapy was a strong effect modifier of calcium and vitamin-D supplementation on colorectal cancer risk. While calcium plus vitamin-D supplementation among women concurrently assigned to estrogen therapies suggested increased risk (Hazard Ratio 5 1.50, 95% CI: 0.96-2.33), among women concurrently assigned to placebos arms of the estrogen trials, calcium plus vitamin-D indicated suggestive benefits (HR 5 0.71, 95% CI: 0.46-1.09) (p-for-estrogen-interaction 5 0.018). Consistent interaction was also found by reported estrogen use (p interaction 5 0.037). Results indicate contrasting effects of calcium and vitamin-D by concurrent estrogen therapy on colorectal cancer risk. Although further clinical and mechanistic studies are warranted, the potential clinical implications of the apparent interaction of estrogen therapy with calcium and vitamin-D supplementation should be recognized. Important biological mechanisms related to the key membrane receptor megalin and estrogen-dependent protein calbindin are discussed. ' 2007 Wiley-Liss, Inc.Key words: vitamin D; calcium; estrogen; colorectal cancer; randomized trial; epidemiology; women; calcitriol; cholecalciferol; megalin In 1980, vitamin D was first proposed to have benefit against colorectal cancer based on ecological studies of colorectal cancer incidence and low sunlight exposure. 1 Vitamin D has been documented to possess a variety of anti-cancer properties, 2 including inhibit growth and induce differentiation and apoptosis of colon tumor cells, 3 as well as shown to be associated with lower risk of colorectal cancer and adenoma in prospective studies. [4][5][6][7] In addition to a meta-analysis of observational studies supporting the relation of vitamin D and lower colorectal cancer risk, 8 a recent meta-analysis of randomized trials indicates vitamin D supplementation likely decreases risk of all-cause mortality, with benefits for cancer thought to be a major explanatory factor. 9 Consistent with a 5 year vitamin D trial that suggested benefits against colorectal cancer mortality, 10 a large randomized trial indeed demonstrated that moderate dose 1,000 IU vitamin D and calcium supplementation substan...

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Need for Additional Calcium to Reduce the Risk of Hip Fracture With Vitamin D Supplementation: Evidence From a Comparative Meta-analysis of Randomized Controlled Trials

Cited by 46 publications

References 0 publications

Milk intake and risk of hip fracture in men and women: A meta-analysis of prospective cohort studies

Milk intake and risk of hip fracture in men and women: A meta-analysis of prospective cohort studies

High-calcium, vitamin D fortified milk is effective in improving bone turnover markers and vitamin D status in healthy postmenopausal Chinese women

Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: Reanalysis of Women's Health Initiative randomized trial

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