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Calcium and Vitamin D: Effects of Isolated Vitamin D Supplementation on Bone Mineral Density and Fracture Reduction

Vitamin D

Assessments of vitamin D supplementation on BMD have produced variable results. Ooms et al. observed that 400 IU of vitamin D for two years improved BMD of the femoral neck in a group of 80-year-old patients. However, distal radius and femoral trochanter BMD did not significantly improve. Dawson-Hughes et al. showed that 400 IU of vitamin D for 12 months was able to attenuate BMD loss in a group of older women, an effect whose significance was driven by benefit seen in the late winter months.

In the Peacock study, no overall effect of 600 IU daily of vitamin D on BMD was observed in an elderly population. Patel et al., assessing the effect of 800 IU daily for 12 months on 70 women (mean age, 47 years), found no significant benefit in any measure of BMD. These results were similar to the prior findings of Hunter et al., who found that two years of vitamin D supplementation with 800 IU produced no benefit in BMD in 58-year-old women. buy cialis soft tabs

Baseline 25-OH-D levels may play a role in determining the BMD benefit associated with vitamin D supplementation. In the Peacock study, the subgroup of patients who consumed less than 720 mg of calcium daily at baseline did exhibit a statistically significant BMD benefit when compared with controls, an effect the authors were able to correlate with increasing 25-OH-D levels. The mild benefit seen in the Ooms study probably occurred through marked improvement of an outright baseline vitamin D deficiency. The lack of a statistically significant treatment effect in the Patel and Hunter studies might be a function of baseline 25-OH-D levels that, at 27.2 and 28 ng/mL, respectively, were already near the 30-ng/mL threshold.

Compelling evidence for the correlation between 25-OH-D status and BMD comes from a non-interventional study of more than 13,000 young patients in the U.S. by Bischoff-Ferrari et al. Conducting a regression analysis of the association between these two factors, these investigators found that in patients with a mean age of 32 to 35 years, BMD increased with increasing serum 25-OH-D levels up to 36 to 40 ng/mL. Within this range, one would have expected better results from the Patel and Hunter studies, which boosted 25-OH-D levels to 37.4 and 42 ng/mL, respectively. Possible reasons for a lack of BMD effect include Patel’s short study duration and Hunter’s baseline calcium intake, which was already near the Dietary Reference Intake (DRI).

For isolated vitamin D supplementation, the lack of a robust effect on BMD has translated to predictably varied results in the most important of all outcome measures—fracture prevention. Lips et al. could not prove a significant benefit of 400 IU of vitamin D in 2,600 elderly Dutch men and women, even with an increase in 25-OH-D levels from 10.8 ng/mL at baseline to almost 25 ng/mL. The study of 438 patients by Peacock, which demonstrated no BMD benefit with 600 IU of vitamin D supplementation, predictably showed no prevention in fracture frequency, even in the low-calcium subgroup. Meyer et al. also noted no fracture reduction with 400 IU of vitamin D daily in almost 1,200 nursing-home residents (average age, 85 years).
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The only study with oral vitamin D supplementation unaccompanied by calcium to show a benefit in fracture incidence was conducted by Trivedi et al. In this study, 2,600 elderly British patients received 100,000-IU capsules of vitamin D every fourth month for five years. This average daily dose of just over 800 IU reduced the incidence of fractures at the hip, wrist, forearm, or vertebrae by an impressive one-third, compared with the rate for controls.

A possible explanation for the lack of a benefit in most of the patients studied might be related to calcium intake. In these four trials, mean calcium intakes were 870 mg, 650 mg, 450 mg, and 742 mg, respectively. The best of these values was roughly two-thirds of the DRI for calcium, a factor that might have inhibited the ability of vitamin D supplementation to enhance bone integrity.

More recently, a meta-analysis of randomized controlled trials compared the fracture-prevention capability of low doses of vitamin D at 400 IU/day with higher doses at 700 to 800
IU/day with varying degrees of calcium supplementation within the groups.86 In the 12 trials analyzed, the range of supplementation varied from nothing to 1,200 mg of calcium per day. Whereas the higher dose of vitamin D appeared to reduce the risk of hip and nonvertebral fractures in ambulatory or institutionalized elderly patients, the lower dose did not.

Despite the positive results with high-dose vitamin D in the ambulatory and institutionalized populations,86 a Cochrane review of more recent trials confirmed the vitamin’s benefit only in institutionalized patients. Once again, this review reiterated Bischoff-Ferrari’s contention that low-dose vitamin D was of no benefit in any population but that high-dose therapy benefited only institutionalized patients, lowering fracture risk by about 20°%.

Of interest is the inextricably linked but independent mechanism whereby vitamin D might be able to reduce the risk of falling by improving a person’s muscle strength and neuro-muscular function. Possibly by activating second messengers and phosphorylation, vitamin D seems to increase muscle protein synthesis. Supplemental vitamin D improves symptoms and function related to neurological manifestations of vitamin D deficiency, such as postural sway, rapid fatigue, psychomotor dysfunction, and difficulty climbing stairs or getting up from chairs.

Effect of Calcium plus Vitamin D on Bone Mineral Density and Fracture Risk participants. However, among the women who were at least 80% compliant with their treatment regimen, fracture risk was reduced in nearly 30%. This significant decrease was identical to that of patients who took no other form of calcium supplementation. Results did not vary according to baseline levels of 25-OH-D. That being said, serum levels were not reassessed after randomization to determine the effect of treatment with 400 IU of vitamin D.

From this group of studies, we can see that comprehensive supplementation with both calcium and vitamin D may have a synergistic effect in patients below benchmark intakes of either or both agents. Indeed, the results appear promising when these “deficient” individuals are able to achieve 25-OH-D levels near or above the proposed goal of 30 ng/mL. eriacta 100 mg

Safety of Calcium and Vitamin D Supplementation

A major consideration in the advocacy of calcium and vitamin D supplementation as a public health policy is the measure of potential for risks compared with benefits. To date, safety analyses have shown that both agents are remarkably safe. In the dozens of trials involving some combination of calcium with or without vitamin D discussed in our article, only the Women’s Health Initiative showed a significant difference in kidney stone formation. Constipation is the predominant adverse effect seen with calcium supplementation; this factor may impair compliance, but it is generally not life-threatening.

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