The final step in assessing the beneficial bone effects of calcium and vitamin D supplementation is to determine outcomes when the two are administered together. Grados et al. gave 192 women with a gross vitamin D deficiency (baseline 25-OH-D level of 7 ng/mL) 800 IU of vitamin D plus 1,200 mg of calcium daily for 12 months. The daily dietary calcium intake of these subjects was 700 mg. The treated group experienced significant lumbar, femoral, and whole-body BMD increases and a three-fold increase in 25-OH-D levels to 22 ng/mL.
A pair of studies by Chapuy, conducted in the early 1990s, echoed these results. In the earlier of the two studies, 1,700 elderly women with a 25-OH-D level of 16 ng/mL and a dietary calcium intake of just over 500 mg/day received 800 IU of vitamin D3 and 1,200 mg of calcium daily for 18 months. BMD improved, and the incidence of fractures was emphatically reduced by 30% to 40%. These results were reproduced in 3,200 women over a 36-month period in the later study. Chapuy et al. then administered the same regimen to almost 600 women with baseline 25-OH-D levels of 8 to 9 ng/mL and a dietary calcium intake of 550 mg daily at the baseline evaluation. A 40% reduction in fracture risk was seen as 25-OH-D levels climbed to exceed 30 ng/mL.
Dawson-Hughes et al. conducted a study with 400 men and women with baseline 25-OH-D values of 33 ng/mL and a dietary calcium intake of 700 mg. They were given supplemental 700 IU of vitamin D and 500 mg of calcium daily for three years. Excellent BMD benefits and a significant reduction in fractures were noted.
Larsen et al. observed a 16% reduction in fracture risk with 400 IU and 1,000 mg of calcium daily in almost 5,000 patients with baseline 25-OH-D levels at about 15 ng/mL.
The findings of two trials seem to contradict this conclusion, but both have caveats. The Randomised .Evaluation of Calcium Or vitamin D3 (RECORD) trial tracked the fracture incidence in 1,300 patients who received 1,000 mg of calcium and 800 IU of vitamin D3. No benefit was observed over a period of almost four years, even in patients with poor baseline calcium intakes and despite an increase in serum 25-OH-D from 15.2 to 25 ng/mL. It is worth noting that nearly half of the original enrollees were excluded on the basis of cognitive impairment; hence, the patients with highest risk of falls were excluded from the trial.
The Women’s Health Initiative tracked BMD and fracture rates in more than 18,000 women who received 1,000 mg of calcium and 400 IU of vitamin D3 daily. No overall benefit was observed despite a mild 6% increase in BMD in the treated.
Osteoporosis increases in prevalence with advancement in age, and the average age of the population in the U.S. is indeed steadily increasing. The costs to our medical system have been substantial to date and only stand to grow in the future. For these reasons, cost-effective therapeutic options today that can prevent or ameliorate the manifestations of this disease state would impart a public health benefit of significant proportions in the future. Table 3 summarizes our recommendations.
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Table 3 Summary of “Pearls” Toward Optimal Utilization of Calcium and Vitamin D
Calcium screening and assessment may be done with baseline and serial 25-hydroxyvitamin D levels:
• Calcidiol (25-OH-D) levels are of benefit in screening for at-risk patients. Levels below 20 ng/mL imply “insufficiency” of vitamin D.
• Calcium with vitamin D therapy should be started to achieve a level of at least 30 ng/mL (but not greater than 60 ng/mL) so that calcium utilization is optimized.
Barring clinical contraindications, calcium along with vitamin D should be given to all “at-risk” individuals:
• All patients taking antiresorptive or osteoblast stimulant therapies so that a substrate is provided to optimize benefit.
• Patients unable to obtain, afford, or tolerate antiresorptive agents or osteoblast stimulants may still benefit from taking calcium with vitamin D.
• The citrate salt shows improved absorption characteristics over the carbonate salt, but the carbonate form may suffice if citrate is too costly or unavailable.
• Calcium citrate is preferred for patients taking potent acid-lowering agents (e.g., proton pump inhibitors), but carbonate may be acceptable if it is always taken with food.
• Patients with end-stage renal disease should avoid calcium citrate because of increased aluminum absorption, but carbonate and acetate salts are safe.
• Doses need not exceed 1 to 1.5 g of elemental calcium per day. If vitamin D supplementation is optimized, even lower doses benefit.
• To ensure compliance, twice-daily dosing is preferred to three times daily.
• Even though the carbonate salt is best given in amounts not exceeding 500 mg per dose because of dose-dependent absorption, citrate salt absorption may not be limited by this threshold.
Vitamin D product and dose:
• Vitamin D3 (cholecalciferol) is preferred to vitamin D2 (ergocalciferol).
• The old standard of 400 to 600 lU/day seems inadequate, especially in the elderly. At least 800 lU/day and probably 1,000 to 1,200 lU/day seem more likely to achieve the desired target 25-0H-D level above 30 ng/mL.
• A daily multivitamin infusion with 400 IU, plus a combination calcium/vitamin D product, should suffice to achieve the desired daily dose of vitamin D, but extra vitamin D tablets may be added at minimal cost.
• Vitamin D may reduce the risk of falls by improving muscle strength.
In terms of calcium supplementation, to ensure maximal absorption and utilization of an ingested dose, calcium citrate may be preferable to calcium carbonate, especially in individuals with achlorhydria or those who are taking potent acid-l owering drugs such as PPIs. Optimal timing of calcium supplementation has been studied, but results are inconclusive. erectalis
Contrary to popular belief, once-daily dosing of the entire DRI of calcium, especially in the evening, may provide benefits that are at least equal to those of divided doses, although this option has not proved definitive. For this reason, as we recognize the need to foster daily compliance for calcium intake, we recommend at least twice-daily divided doses of calcium sufficient to meet the current DRI for each age group.
As demonstrated by numerous studies showing disturbingly low levels of serum 25-OH-D in a vast array of populations, vitamin D deficiency is a public health problem. Supplementation with oral vitamin D3 can be more effective than with vitami n D2; the latter is less reliably absorbed and has a less robust effect on serum 25-OH-D levels.
As for dosage, the effect of daily supplementation with 400 IU of vitamin D on serum 25-OH-D levels, BMD, and the incidence of fractures has proved to be largely inadequate. Dosing with 600 IU of vitamin D daily seems to provide a better conducted infrequently because of concerns of toxicity, even though toxicity has been noted only rarely. In 1992, one paper reported a series of cases of hypervitaminosis D associated with milk consumption. However, the eight patients who experienced markedly elevated 25-OH-D concentrations might have been drinking milk that was erroneously fortified with more than 100,000 IU of vitamin D per glass, supplementation that is clearly excessive. Adams and Lee found that serum 25-OH-D levels in the range of 70 ng/mL caused hypercalcemia and hypercalciuria in a group of 40 people in Los Angeles, although this finding is aberrant when considered with other toxicity studies.
Heaney et al. applied aggressive dosing regimens to 67 Nebraskan men with baseline 25-OH-D levels of 26 to 28 ng/mL. The subjects were stratified to receive 1,000 IU; 2,000 IU; 5,000 IU; or 10,000 IU of vitamin D daily for 20 weeks during the winter. The men who received 1,000 IU showed an increase in 25-OH-D to only 33.6 ng/mL, the 2,000-IU group to 64.24 ng/mL, and the 10,000-IU group to 89.6 ng/mL. Serum calcium levels were carefully monitored in the two higher dosage groups, with no significant changes observed from baseline. From this trial, one could infer that the true upper level of the reference range was at least 90 ng/mL, although more trials are needed to establish safety at these chronic, elevated levels.
An apparent trend in vitamin D administration, mentioned in the Heaney study and in a study by Trang, is that serum 25-OH-D levels increase linearly with a given level of supplementation only to a certain point, at which time they achieve a plateau. This phenomenon, which may result from a relative decrease in liver hydroxylation with higher blood levels of vitamin D, should help to assuage fears of overt vitamin D intoxication, even with doses several times as large as the current Adequate Intake.
Current U.S. governmental recommendations advise against daily doses above 2,000 IU. This sentiment emerged after a study showed hypercalcemia in a handful of patients who had consumed 3,800 IU of vitamin D3 for three months. Vieth et al. sought to address the validity of this recommendation by giving 61 middle-aged men and women either 1,000 IU or 4,000 IU of vitamin D3 for two to five months, bringing serum 25-OH-D levels from 16.4 ng/mL at baseline to 27.5 ng/mL and 38.6 ng/mL in the two cohorts, respectively. The investigators noted no significant increases in serum calcium or urinary calcium excretion during the dosing period. kamagra soft tablets
In summary, calcium and vitamin D supplementation appear to be safe for most people. We recommend periodic laboratory monitoring of serum calcium and phosphorus levels in patients whose calcium supplementation, with or without vitamin D, is higher than the values recommended. Because laboratory monitoring of these values is a routine practice among primary care practitioners, it should add no appreciable cost to the health care system.