The elevation of parathyroid hormone (PTH) levels in response to below normal serum calcium levels has a deleterious effect on bone mineral density (BMD). In this situation, calcium is leached from bone to supplement the hypo-calcemic condition. Oral calcium can suppress this elevation, but establishing an optimal calcium dose for this purpose is still challenging.
Although the data indicate some degree of variability in potency, substantial suppression of PTH secretion with oral calcium supplementation has been achieved with single doses as low as 250 mg. (We are expressing all doses of calcium products as elemental calcium.) Greater suppression of PTH secretion occurs with higher singular calcium doses, but the ability of the GI tract to tolerate single doses as high as 1,000 to 2,000 mg might be a concern.
Another consideration with oral calcium supplementation is the timing of doses. PTH secretion and other biochemical markers of bone resorption such as collagen breakdown products have a circadian rhythm that peaks at night. Blumsohn et al. found that 1,000 mg of calcium administered at 2300 hours (11 p.m.) was superior at blunting the typical nighttime increase in PTH compared with the same dose given at 0800 (8 a.m.). However, the accompanying decrease in the 24-hour urinary recovery of bone breakdown products in the group taking calcium at 11 p.m. did not achieve statistical significance.
Karkkainen et al. did not find a significant 24-hour difference in suppression of PTH secretion between groups receiving equal amounts of calcium at 9 a.m., compared with 9 p.m., although both calcium groups were superior to placebo. This study failed to show a difference in bone resorption markers in either group compared with placebo.
In a study by Scopacasa et al., calcium carbonate 500 mg twice daily and 1,000 mg once daily, when given to early postmenopausal women, reduced 24-hour markers of bone resorption by approximately 6% to 10% over placebo. This reduction was similar between treatment groups. No PTH values were measured as part of this study.
These results loosely correlated with the work of Ginty et al. In the Ginty study, a 14% to 16% reduction in bone resorption markers over placebo was observed in women receiving 400 mg of calcium (as lactate gluconate and carbonate) twice daily in addition to diet containing 800 mg of calcium. This study also lacked data on PTH. buy viagra uk
In a study by Fardellone et al., calcium carbonate 600 mg twice daily produced decreases in markers of bone resorption markers by 16% to 18%.
On the basis of these studies and in conjunction with current National Academy of Sciences and NIH recommendations for calcium intake for men and women, although it may depend on the calcium salt, a daily regimen of 1,000 to 1,500 mg of elemental calcium, divided twice daily, seems to optimize the efficiency of calcium absorption and may provide a significant suppression of PTH and markers of bone resorption during most of the day. Daily doses that exceed these current standards probably provide marginal incremental reductions in markers for PTH and may bring with them problems of increased cost, decreased tolerance, and reduced compliance. As we discuss later, far greater advantages may be gained by optimizing concomitant vitamin D than by pushing the calcium dose to higher levels.
Effect of Isolated Calcium Supplementation on Bone Mineral Density and Fracture Reduction intake. Among a “late-menopause” subgroup explored by Dawson-Hughes et al., nearly every group studied showed slower BMD loss when the baseline calcium consumption was 400 mg/day or less. The women consuming from 400 to 650 mg/day, when given calcium supplements, showed no BMD improvement at any site when compared with placebo, a compelling finding.
In a 1996 study by Recker et al., increases in forearm BMD were significant with 1,200 mg of calcium per day in the “previous fracture” cohort but not in the cohort without prior fractures. Despite a baseline calcium intake that appeared to be uniformly poor (approximately 420 mg/day), the authors attributed this effect to a lesser baseline BMD attributable to “nutritional calcium deficiency” in the former group, compared with the latter.
In a study by Storm, a calcium intake of less than 800 mg was a criterion for inclusion; as noted previously, the effects of oral calcium supplementation on BMD were robust. This left Reid and colleagues as the only investigators who observed no difference in results among women when they were classified according to their baseline calcium intakes. Thus, even though the findings are inconclusive, it appears that the women with the poorest diet in terms of daily calcium intake stand to benefit the most from calcium supplementation. official canadian pharmacy
In contrast to studies that evaluated calcium benefits in terms of BMD, few trials have explored the rate of incident fractures. The NHANES I Epidemiologic Follow-up Study observed both men and women for a mean of 14.6 years and assessed the rate of incident fractures on the basis of quartiles (0%^25%, 26%^50%, 51%^75%, and 76«00%)of dietary calcium intake. The relative risk of hip fracture was lower in the subjects consuming the higher three quartiles of calcium, but the findings were not statistically significant and did not result in a linear trend.
In Recker’s randomized, controlled trial of patients with poor calcium intake at baseline, a statistically significant decrease in repeated vertebral fractures was noted with 1,200 mg of oral calcium supplementation daily for 4.3 years. Cheval-ley et al. showed a significant decrease in the rate of vertebral fractures in patients who had been randomly assigned to receive 800 mg of oral calcium daily.
In a randomized study of patients receiving 1,200 mg of calcium carbonate daily or placebo, Prince et al. noted that the risk of fractures at all sites decreased by an impressive rate of 34% in patients taking at least 80% of their doses. This effect was even more impressive, considering their baseline calcium intake of about 900 mg daily.
The only trial to deviate from this trend, by Peacock et al., found that 750 mg of elemental calcium daily had no statistically significant effect, when compared with placebo, on the rate of all fractures. viagra soft
Although the data on fracture prevention seem to favor the benefit of calcium supplementation, the data on BMD are equivocal. Unfortunately, the lack of consistent effect in these studies may be a result of factors beyond simple calcium availability, such as the presence of calcium-regulating hormones. A venture into the data concerning vitamin D supplementation may yield some clarity on this issue.