Calcium - Vitacost

Calcium

Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women [see comments]

Ann Intern Med, 115(7):505-12 1991 Oct 1

OBJECTIVES: To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss and whether rates of change in hard- and soft-tissue mass vary during the year. DESIGN: Double-blind, placebo-controlled, 1-year trial in 249 women in which equal numbers of women were randomized to either placebo or 400 IU of vitamin D daily. All women received 377 mg/d of supplemental calcium largely as calcium citrate malate. PATIENTS: Healthy, ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d. MEASUREMENTS: Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25-hydroxyvitamin D levels were highest and lowest. Period 1 was June-July to December-January and period 2 was December-January to the next June-July. Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2. MAIN RESULTS: In the placebo group, spinal bone mineral density increased in period 1, decreased in period 2, and sustained no net change. Women treated with vitamin D had a similar spinal increase in period 1 (1.46% compared with 1.40% in placebo), less loss in period 2 (-0.54% compared with -1.22%, CI for the difference, 0.05% to 1.31%, P = 0.032) and a significant overall benefit (0.85% compared with 0.15%, CI for the difference, 0.03% to 1.37%, P = 0.04). In period 2, 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group. Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall. CONCLUSIONS: At latitude 42 degrees, healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily. A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown. Observed changes in bone as well as in fat and lean tissue appear to be related to season.

The effect of calcium supplementation and Tanner stage on bone density, content and area in teenage women.

Osteoporos Int, 6(4):276-83 1996

One hundred and twelve Caucasian girls, 11.9 +/- 0.5 years of age at entry, were randomized into a 24-month, double-masked, placebo-controlled trial to determine the effect of calcium supplementation on bone mineral content, bone area and bone density. Supplementation was 500 mg calcium as calcium citrate malate (CCM) per day. Controls received placebo pills, and compliance of both groups averaged 72%. Bone mineral content, bone mineral area and bone mineral density of the lumbar spine and total body were measured by dual energy X-ray absorptiometry (DXA). Calcium intake from dietary sources averaged 983 mg/day for the entire study group. The supplemented group received, on average, an additional 360 mg calcium/day from CCM. At baseline and after 24 months, the two groups did not differ with respect to anthropometric measurements, urinary reproductive hormone levels or any measurement of pubertal progression. The supplemented group had greater increases of total body bone measures: content 39.9% versus 35.7% (p = 0.01), area 24.2% versus 22.5% (p = 0.15) and density 12.2% versus 10.1% (p = 0.005). Region-of-interest analyses showed that the supplemented group had greater gains compared with the control group for bone mineral density, content and area. In particular, in the lumbar spine and pelvis, the gains made by the supplemented group were 12%-24% greater than the increases made by the control group. Bone acquisition rates in the two study groups were further compared by subdividing the groups into those with below- or above-median values for Tanner score and dietary calcium intake. In subjects with below-median Tanner scores, bone acquisition was not affected by calcium supplementation or dietary calcium level. However, the calcium supplemented subjects with above-median Tanner had higher bone acquisition rates than the placebo group with above-median Tanner scores. Relative to the placebo group, the supplemented group had increased yearly gains of bone content, area and density which represented about 1.5% of adult female values. Such increases, if held to adult skeletal maturity, could provide protection against future risk of osteoporotic fractures.

Effect of calcium supplementation on blood pressure in children [see comments]

J Pediatr, 127(2):186-92 1995 Aug

OBJECTIVE: To evaluate the effect of calcium supplementation on blood pressure in children. DESIGN: Randomized, double-masked, placebo-controlled trial. SETTING AND PARTICIPANTS: One hundred one fifth-grade students in one inner-city school. INTERVENTION: Each child consumed 480 ml of juice beverages, containing either no calcium or 600 mg calcium (as calcium citrate malate) daily for 12 weeks. MEASUREMENTS: At baseline we obtained nutrient data from three sets of 2-day food records on each subject. We measured blood pressure four times on each of three weekly sittings at baseline and at follow-up. Using multiple linear regression analysis, we compared mean blood pressure change in the intervention group with that in the placebo group. RESULTS: There were 50 girls and 51 boys; 61 subjects were black. At baseline, mean age was 11.0 years, systolic and diastolic blood pressures were 101.7 and 57.7 mm Hg, daily total energy intake was 1966 kcal, and calcium intake was 827 mg. With control for age, height, hours of television watched, and baseline blood pressure, systolic blood pressure increased 1.0 mm Hg in the intervention group and 2.8 mm Hg in the placebo group (effect estimate = -1.8 mm Hg; 95% confidence interval -4.0, 0.3). In black subjects the intervention effect estimate was -2.0 mm Hg (95% confidence interval -4.4, 0.4). From lowest to highest quartile of baseline calcium intake (per 1000 kcal), the intervention effect estimates were -3.5, -2.8, -1.3, and 0.0 mm Hg (p for trend = 0.009). There was little effect on diastolic blood pressure. CONCLUSION: These data suggest a blood pressure-lowering effect of calcium supplementation in children, especially in subjects with low baseline calcium intake.

Dietary calcium, vitamin D, and the risk of colorectal cancer in Stockholm, Sweden.

Cancer Epidemiol Biomarkers Prev, 337(10):897-900 1996 Nov

The epidemiology of large bowel cancer suggests an etiological role for dietary factors. Although the evidence is inconsistent, several studies have suggested an inverse association between dietary vitamin D or calcium and colorectal cancer risk. We conducted a population-based case-control study to examine the relationship between dietary vitamin D and calcium and colorectal cancer among residents of Stockholm, Sweden. Between January 1986 and March 1988, 352 cases of colon cancer and 217 cases of rectal cancer diagnosed among living persons residing in Stockholm County were identified via a cancer surveillance network established among all the hospitals in Sweden and the Stockholm Regional Cancer Registry. Controls (512) were randomly selected from a computerized population registry. Dietary intake was assessed using a quantitative food frequency questionnaire focusing on average consumption during the preceding 5 years. Supplemental intake of vitamin D and calcium was not ascertained. Logistic regression was used to calculate odds ratios (ORs) as the measure of association between the exposure of interest (vitamin D or calcium) and cancer risk. Increasing levels of dietary vitamin D were inversely associated with the risk of colorectal cancer. The association was somewhat more pronounced for cancers of the rectum [OR, 0.5; 95% confidence interval (CI), 0.3-0.9 between the highest and lowest quartiles] than for cancers of the colon (OR, 0.6; 95% CI, 0.4-1.0) after adjustment for age, sex, and total caloric and protein intake. Dietary calcium was not associated with the adjusted risk of colon (OR, 1.2; 95% CI, 0.7-2.1) or rectal cancer (OR, 1.0; 95% CI, 0.5-1.9). Further adjustments for fat and dietary fiber intake, body mass index, and physical activity had little or no effect on the results. These results suggest that dietary vitamin D may reduce the risk of large bowel cancer, particularly rectal cancer. In addition, although some of the previous data suggested a protective effect for calcium against cancers of the large bowel, we could not document such an effect.

Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people.

Scand J Rheumatol Suppl, 88(19):75-8; discussion 79-80 1996

For a 50-year old caucasian woman today, the risk of a hip fracture over her remaining lifetime is about 17%. Tomorrow the situation will clearly be worse because the continual increase in life expectancy will cause a 3-fold rise in worldwide fracture incidence over the next 60 years, particularly in women, but also in men. In addition, a secular increase in the incidence of hip fractures in individuals of the same age has been noted in both sexes by several investigators, and the cost of hip fractures is expected to dramatically increase in the next decades. Consequently, preventive strategies are urgently required. A great deal has been learned in recent years about the risk factors for hip fracture, the pathophysiology of this fracture, and the prediction of fracture risk, particularly through bone mass measurements on the hip and biochemical evaluations of parathyroid and vitamin D status. The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. A substantial femoral bone loss continues throughout the old age, with a continuous and exponential increase in the risk of hip fracture, and any reduction or arrest of this loss will induce an important reduction in the incidence of hip fractures. A preventive effect on the risk of hip fracture may be partly achieved by using long term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for a late prevention in elderly people. Vitamin D insufficiency and deficit in calcium intake are very common in elderly people living either in institutions or at home, particularly in Europe where dairy products are not fortified with vitamin D. The cumulative response to this deficit in calcium intake and low vitamin D status is a negative calcium balance which stimulates parathyroid hormone secretion. In 300 residents of nursing homes, we recently found a significant negative correlation between serum 25 OHD and log serum PTH after age-adjustment. In addition, in 446 elderly women living at home in 5 French cities and selected from the voting lists, we also found an age-adjusted relationship between serum 25 OHD and PTH concentrations. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3-year controlled prospective study that the daily use of these supplements (1.2 g of calcium and 800 IU of vitamin D3) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced of 23% (intention-to-treat analysis) the number of hip fractures and other non vertebral fractures. In parallel, serum perathyroid hormone concentration was reduced of 28% and low serum 25-hydroxyvitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased 2.7% the vitamin D3-calcium group and decreased 4.6% in the placebo group (p < 0.001). This prevention is safe and can be recommended in people living in institutions. It could be also useful in other elderly subjects particularly at risk because of a low calcium intake, an absence of solar exposure and a previous history of falls. From the data of our study we assessed the economic consequences in terms of medical cost of this prevention. In case of treatment of all women living in nursing homes in France, this would saved FF 150000000 per year, the economic balance of prevention becoming positive as soon as the age of the beginning of the prevention reaches 73.5 years. It is now possible to partly stop bone loss in elderly people and it is never too late to prevent hip fractures with calcium and vitamin D supplements.

Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D.

Am J Clin Nutr, 61(5):1140-5 1995 May

We conducted a study to determine whether increasing vitamin D intake above the recommended dietary allowance (RDA) of 5.0 micrograms (200 IU)/d reduces bone loss in healthy postmenopausal women residing at latitude 42 degrees N. In this double-blind, randomized 2-y trial, we enrolled 247 healthy ambulatory postmenopausal women who consumed an average of 2.5 micrograms (100 IU) vitamin D/d in their usual diets. The women were given either 2.5 micrograms (100 IU) or 17.5 micrograms (700 IU) vitamin D/d. All women received 500 mg supplemental calcium per day as citrate malate. Duplicate hip and spine and single whole-body scans were performed by dual-energy x-ray absorptiometry at 6-mo intervals selected to flank the periods when 25-hydroxycholecalciferol (calcidiol) concentrations are highest (summer/fall) and lowest (winter/spring). Plasma calcidiol and serum osteocalcin were measured in these seasons in year 1. Both treatment groups lost bone mineral density from the femoral neck, but the 17.5-micrograms group lost less than (-1.06 +/- 0.34%; mean +/- SE) the 2.5-micrograms group (-2.54 +/- 0.37%, P = 0.003). Seventy percent of the benefit each year occurred in winter/spring and 30% in summer/fall. Changes in spinal and whole-body bone densities did not differ by treatment group and were minimal after 2 y. Serum osteocalcin and plasma calcidiol (2.5-micrograms group only) fluctuated with season. In conclusion, in healthy, calcium-supplemented, postmenopausal women residing at latitude 42 degrees N, an intake of 5.0 micrograms (200 IU) vitamin D/d is sufficient to limit bone loss from the spine and whole body but it is not adequate to minimize bone loss from the femoral neck.

Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group.

N Engl J Med, 1999 Jan, 340:2, 101-7

BACKGROUND AND METHODS: Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period. RESULTS: The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 percent confidence interval, 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31 percent) and 159 subjects in the placebo group (38 percent); the adjusted risk ratio was 0.81 (95 percent confidence interval, 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 percent confidence interval, 0.60 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake. CONCLUSIONS: Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas.

Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older [see comments]

N Engl J Med, 337(10):670-6 1997 Sep 4

BACKGROUND: Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons. METHODS: We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density, biochemical measures of bone metabolism, and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home. They received either 500 mg of calcium plus 700 IU of vitamin D3 (cholecalciferol) per day or placebo. Bone mineral density was measured by dual-energy x-ray absorptiometry, blood and urine were analyzed every six months, and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records. RESULTS: The mean (+/-SD) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows: femoral neck, +0.50+/-4.80 and -0.70+/-5.03 percent, respectively (P=0.02); spine,+2.12+/-4.06 and +1.22+/-4.25 percent (P=0.04); and total body, +0.06+/-1.83 and -1.09+/-1.71 percent (P<0.001). The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year, but it was significant only for total-body bone mineral density in the second and third years. Of 37 subjects who had nonvertebral fractures, 26 were in the placebo group and 11 were in the calcium-vitamin D group (P=0.02). CONCLUSIONS: In men and women 65 years of age or older who are living in the community, dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck, spine, and total body over the three-year study period and reduced the incidence of nonvertebral fractures.

Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial [see comments]

Ann Intern Med, 125(12):961-8 1996 Dec 15

BACKGROUND: Therapy with low-dose corticosteroids is commonly used to treat allergic and autoimmune diseases. Long-term use of corticosteroids can lead to loss of bone mineral density and higher risk for vertebral fractures. Calcium and vitamin D3 supplementation is rational therapy for minimizing bone loss, but little evidence for its effectiveness exists. OBJECTIVE: To assess 1) the effects of supplemental calcium and vitamin D3 on bone mineral density of patients with rheumatoid arthritis and 2) the relation between the effects of this supplementation and corticosteroid use. DESIGN: 2-year randomized, double-blind, placebo-controlled trial. SETTING: University outpatient-care facility. PATIENTS: 96 patients with rheumatoid arthritis, 65 of whom were receiving treatment with corticosteroids (mean dosage, 5.6 mg/d). INTERVENTION: Calcium carbonate (1000 mg/d) and vitamin D3 (500 IU/d) or placebo. MEASUREMENTS: Bone mineral densities of the lumbar spine and femur were determined annually. RESULTS: Patients receiving prednisone therapy who were given placebo lost bone mineral density in the lumbar spine and trochanter at a rate of 2.0% and 0.9% per year, respectively. Patients receiving prednisone therapy who were given calcium and vitamin D3 gained bone mineral density in the lumbar spine and trochanter at a rate of 0.72% (P = 0.005) and 0.85% (P = 0.024) per year, respectively. In patients receiving prednisone therapy, bone mineral densities of the femoral neck and the Ward triangle did not increase significantly with calcium and vitamin D3. Calcium and vitamin D3 did not improve bone mineral density at any site in patients who were not receiving corticosteroids. CONCLUSION: Calcium and vitamin D3 prevented loss of bone mineral density in the lumbar spine and trochanter in patients with rheumatoid arthritis who were treated with low-dose corticosteroids.

Calcium, vitamin D, and the occurrence of colorectal cancer among women.

J Natl Cancer Inst, 88(19):1375-82 1996 Oct 2

BACKGROUND: Despite evidence from animal studies for a protective effect of higher calcium and possibly vitamin D intake against colorectal cancer, epidemiologic studies have been inconclusive. PURPOSE: We investigated the associations between the intake of calcium and vitamin D and the occurrence of colorectal cancer. METHODS: In a prospective study, 89 448 female registered nurses who were free of cancer responded to a mailed, semiquantitative food-frequency questionnaire in 1980; dietary information was updated in 1984 and 1986. Through 1992, 501 incident cases of colorectal cancer (396 colon and 105 rectal cancers) were documented. As measures of exposure, we used nutrient intake in 1980 and also two measures of long-term intake on the basis of the three questionnaires: the average of intakes from the three questionnaires and consistent intakes, which were defined as high if women were in the upper tertile on all questionnaires and low if they were in the lower tertile on all questionnaires. To further characterize long-term intake, we conducted analyses excluding women who reported a change in their consumption of milk (primary source of calcium and vitamin D) in the 10 years prior to 1980. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the lowest quintile of intake as a reference. The Mantel extension test was used to evaluate linear trends across the categories of nutrient intake. In multivariate analyses, the trends were tested with use of the medians of the intake as a continuous variable in the logistic model. The P values for the trends were two-sided. RESULTS: On the basis of the data from the 1980 questionnaire alone, the multivariate RR for colorectal cancer for women in the upper versus the lower quintile were 0.80 (95% CI = 0.60-1.07) for dietary calcium, 0.84 (95% CI = 0.63-1.13) for dietary vitamin D (from foods only), and 0.88 (95% CI = 0.66-1.16) for total vitamin D (from foods and supplements). After the exclusion of women who reported a change in their milk intake, the RRs for colorectal cancer for the highest versus the lowest categories of average intake were 0.74 (95% CI = 0.36-1.50) for dietary calcium, 0.72 (95% CI = 0.34-1.54) for dietary vitamin D, and 0.42 (95% CI = 0.19-0.91) for total vitamin D. The corresponding RRs for the consistency analyses were 0.70 (95% CI = 0.35-1.39) for dietary calcium, 0.59 (95% CI = 0.30- 1.16) for dietary vitamin D, and 0.33 (95% CI = 0.16-0.70) for total vitamin D. CONCLUSIONS: These findings do not support a substantial inverse association between calcium intake and risk of colorectal cancer, but an inverse association between intake of total vitamin D and risk of colorectal cancer was suggested. IMPLICATIONS: Available evidence does not warrant an increase in calcium intake to prevent colon cancer, but longer-term studies of both calcium and especially vitamin D in relation to colorectal cancer risk are needed.

A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women.

N Engl J Med, 323(13):878-83 1990 Sep 27

Background. The effectiveness of calcium in retarding bone loss in older postmenopausal women is unclear. Earlier work suggested that the women who were most likely to benefit from calcium supplementation were those with low calcium intakes. Methods. We undertook a double-blind, placebo-controlled, randomized trial to determine the effect of calcium on bone loss from the spine, femoral neck, and radius in 301 healthy postmenopausal women, half of whom had a calcium intake lower than 400 mg per day and half an intake of 400 to 650 mg per day. The women received placebo or either calcium carbonate or calcium citrate malate (500 mg of calcium per day) for two years. Results. In women who had undergone menopause five or fewer years earlier, bone loss from the spine was rapid and was not affected by supplementation with calcium. Among the women who had been postmenopausal for six years or more and who were given placebo, bone loss was less rapid in the group with the higher dietary calcium intake. In those with the lower calcium intake, calcium citrate malate prevented bone loss during the two years of the study; its effect was significantly different from that of placebo (P less than 0.05) at the femoral neck (mean change in bone density [+/- SE], 0.87 +/- 1.01 percent vs. -2.11 +/- 0.93 percent), radius (1.05 +/- 0.75 percent vs. -2.33 +/- 0.72 percent), and spine (-0.38 +/- 0.82 percent vs. -2.85 +/- 0.77 percent). Calcium carbonate maintained bone density at the femoral neck (mean change in bone density, 0.08 +/- 0.98 percent) and radius (0.24 +/- 0.70 percent) but not the spine (-2.54 +/- 0.85 percent). Among the women who had been postmenopausal for six years or more and who had the higher calcium intake, those in all three treatment groups maintained bone density at the hip and radius and lost bone from the spine. Conclusions. Healthy older postmenopausal women with a daily calcium intake of less than 400 mg can significantly reduce bone loss by increasing their calcium intake to 800 mg per day. At the dose we tested, supplementation with calcium citrate malate was more effective than supplementation with calcium carbonate.

Calcium supplementation and increases in bone mineral density in children [see comments]

N Engl J Med, 93(2):82-7 1992 Jul 9

BACKGROUND. Increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. Whether the increase is due to the calcium content of milk, however, is not certain. METHODS. We conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean [+/- SD] age, 10 +/- 2 years; range, 6 to 14). In each pair, one twin served as a control for the other; 45 pairs completed the study. Bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years). RESULTS. The mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). Among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent [95 percent confidence interval, 1.5 to 8.7 percent]; distal radius, 3.8 percent [95 percent confidence interval, 1.4 to 6.2 percent]) and in the lumbar spine (increase, 2.8 percent [95 percent confidence interval, 1.1 to 4.5 percent]) after three years; the differences in the increases at two of three femoral sites approached significance (Ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). Among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit. CONCLUSIONS. In prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. If the gain persists, peak bone density should be increased and the risk of fracture reduced.

Acute biochemical variations induced by two different calcium salts in healthy perimenopausal women.

Calcif Tissue Int, 57(3):175-7 1995 Sep

Despite the potential utility of calcium supplementation and the availability of many calcium supplements in the market, there are few data concerning the absorbability of different calcium salts in different conditions. We have compared the acute metabolic responses following oral administration of calcium citrate (CC) or calcium gluconolactate and carbonate (CGC) given to 20 healthy perimenopausal women (aged 48-55 years). Ten women received two effervescent tablets of CC (each containing 500 mg of calcium) and 10 women received two effervescent tablets of CGC (each containing 500 mg of calcium). Before and on an hourly basis for 6 hours, serum total and ionized calcium, phosphate, and immunoreactive parathyroid hormone (iPTH) were measured. Urinary calcium and creatinine were also measured. Both calcium salts induced significant increase in serum total and ionized calcium and in urinary calcium excretion; they also significantly reduced circulating levels of iPTH. The analysis of ionized calcium and iPTH response curves to CC and CGC administration revealed a significantly greater bioavailability of CC compared with CGC. Our data suggest that CC could be prefered to CGC for its characteristics of absorbability and bioavailability.

Calcium absorption and achlorhydria.

N Engl J Med, 1985 Jul 11, 313:2, 70-3

Defective absorption of calcium has been thought to exist in patients with achlorhydria. I compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement.

Citrate and renal calculi: new insights and future directions.

Am J Kidney Dis, 1991 Apr, 17:4, 420-5

Citrate is pathogenetically important in stone formation, because it retards the crystallization of stone-forming calcium salts and because its level in urine is low in many patients with nephrolithiasis. Potassium citrate is useful therapeutically, because it can often restore normal urinary citrate. Hypocitraturia often results from dietary aberrations, including sodium excess, and exaggerated intake of animal proteins. Hypocitraturia is frequently accompanied by a low net gastrointestinal absorption of alkali. New drugs are under development as improvements or refinements of currently available potassium citrate. They are potassium citrate 10-mEq-tablet preparation, effervescent calcium citrate, and potassium-magnesium citrate.

Limited risk of kidney stone formation during long-term calcium citrate supplementation in nonstone forming subjects.

J Urol, 1994 Aug, 152:2 Pt 1, 324-7

The physiological and physicochemical effects of long-term calcium citrate supplementation (25 mmol. calcium per day) were assessed in 7 normal premenopausal women. Calcium citrate increased urinary calcium from 3.27 +/- 0.42 mmol. per day (standard deviation) before treatment to 5.16 +/- 0.75 mmol. per day after 1-month of treatment (p < 0.0125). After 3 months of treatment urinary calcium decreased from the 1-month value to 4.54 +/- 0.67 mmol. per day (p < 0.0125) but remained higher than the pretreatment value (p < 0.0125). Fractional intestinal calcium absorption and serum 1,25-dihydroxyvitamin D levels decreased marginally at 1 month of calcium citrate therapy, from 0.457 +/- 0.092 to 0.374 +/- 0.035 (p < 0.05) and from 103 +/- 7 to 77 +/- 14 pmol./l. (p < 0.05), respectively. After 3 months of treatment fractional intestinal calcium absorption decreased further to 0.341 +/- 0.061 (p < 0.0125 compared to pretreatment), whereas serum 1,25-dihydroxyvitamin D remained unchanged at 82 +/- 14 pmol./l. Calcium citrate treatment decreased urinary phosphorus levels significantly from 18.9 +/- 3.3 to 15.0 +/- 2.5 mmol. per day (p < 0.0125) and 14.0 +/- 2.5 mmol. per day (p < 0.05) at 1 and 3 months, respectively. Mean urinary oxalate decreased by 15 to 20% and urinary citrate increased marginally during treatment. Urinary saturation of calcium oxalate and brushite did not change during calcium citrate therapy, except at 1 month when the saturation of calcium oxalate increased marginally. The inhibitory activity of urine against spontaneous nucleation of calcium oxalate and brushite (formation product) did not change during treatment. In conclusion, long-term calcium citrate supplementation in normal subjects does not increase the propensity for crystallization of calcium salts in the urine. This protective effect is probably due to the attenuated increase in urinary calcium excretion (from a decrease in fractional intestinal calcium absorption), a decrease in urinary phosphorus and an increase in urinary citrate.

Different dietary calcium intake and relative supersaturation of calcium oxalate in the urine of patients forming renal stones.

Clin Sci (Colch), 93(3):257-63 1997 Sep

1. Dietary calcium restriction, an efficient practice in reducing urinary calcium excretion, has been reported to induce either an increase or no change in oxalate excretion, questioning its use in hypercalciuric stone-forming patients. In addition, calcium restriction has been previously demonstrated to induce other urinary changes which might influence the relative supersaturation of calcium oxalate. So the overall effect of calcium deprivation on the relative supersaturation of calcium oxalate is unpredictable. 2. The aim of the study was to evaluate the effect of dietary calcium restriction on the relative supersaturation of calcium oxalate in the urine of stone-forming patients utilizing a computer methodology which takes into account the main soluble complex species of oxalate. 3. We studied 34 stone-forming patients on both a free-choice diet, whose Ca and oxalate content (24 and 1.2 mmol respectively) was assessed by dietary inquiry, and after 30 days on a prescribed low-calcium and normal oxalate diet (11 and 1.1 mmol respectively). Under both conditions, the excretion of the main urinary parameters related to dietary composition, electrolytes, oxalate and daily citrate urinary excretion, were measured. The relative supersaturation of calcium oxalate was calculated by means of an iterative computer method which takes into account the main soluble complex species on which the solubility of calcium oxalate is dependent. In addition, intact parathyroid hormone and 1,25-dihydroxyvitamin D blood levels were also evaluated. In 13 of the patients intestinal calcium absorption was evaluated during both a free- and a low-calcium diet, utilizing kinetics methodology. 4. The low-calcium diet induced, together with an expected reduction of calcium excretion, a marked increase in oxalate urinary output. This finding was independent of the presence or otherwise of hypercalciuria and of the serum levels of parathyroid hormone and vitamin D. Intestinal calcium absorption was also stimulated by calcium deprivation and its levels were well correlated with oxalate excretion. Minor changes in magnesium and citrate excretion were also observed. The overall effect on the relative supersaturation of calcium oxalate consisted in a substantial increase in this parameter during the low-calcium diet. 5. In conclusion, our data reinforce the concept that dietary calcium restriction has potentially deleterious effects on lithogenesis, by increasing the relative supersaturation of calcium oxalate.

Combined calcium and vitamin D supplementation reduces bone loss and fracture incidence in older men and women.

Nutr Rev, 53(5 Pt 1):148-50 1998 May

A recent supplementation study of 389 men and women, over the age of 65 years was conducted to address the impact of combined calcium and vitamin D supplementation on nonvertebral fracture incidence and maintenance of bone mass. Daily supplementation with 500 mg calcium and 700 IU vitamin D for 3 years moderately reduced bone loss at several sites and significantly decreased the rate of nonvertebral fractures, compared with a placebo group. Optimal intake of both calcium and vitamin D may be an easily implemented strategy to maintain existing bone mass and reduce the risk of fracture in older men and women.

Clinical practice guidelines for the diagnosis and management of osteoporosis. Scientific Advisory Board, Osteoporosis Society of Canada.

CMAJ, 155(8):1113-33 1996 Oct 15

OBJECTIVE: To recommend clinical practice guidelines for the assessment of people at risk for osteoporosis, and for effective diagnosis and management of the condition. OPTIONS: Screening and diagnostic methods: risk-factor assessment, clinical evaluation, measurement of bone mineral density, laboratory investigations. Prophylactic and corrective therapies: calcium and vitamin D nutritional supplementation, physical activity and fall-avoidance techniques, ovarian hormone therapy, bisphosphonate drugs, other drug therapies. Pain-management medications and techniques. OUTCOMES: Prevention of loss of bone mineral density and fracture; increased bone mass; and improved quality of life. EVIDENCE: Epidemiologic and clinical studies and reports were examined, with emphasis on recent randomized controlled trials. Clinical practice in Canada and elsewhere was surveyed. Availability of treatment products and diagnostic equipment in Canada was considered. VALUES: Cost-effective methods and products that can be adopted across Canada were considered. A high value was given to accurate assessment of fracture risk and osteoporosis, and to increasing bone mineral density, reducing fractures and fracture risk and minimizing side effects of diagnosis and treatment. BENEFITS, HARMS AND COSTS: Proper diagnosis and management of osteoporosis minimize injury and disability, improve quality of life for patients and reduce costs to society. Rationally targeted methods of screening and diagnosis are safe and cost effective. Harmful side effects and costs of recommended therapies are minimal compared with the harms and costs of untreated osteoporosis. Alternative therapies provide a range of choices for physicians and patients. RECOMMENDATIONS: Population sets at high risk should be identified and then the diagnosis confirmed through bone densitometry. Dual-energy x-ray absorptiometry is the preferred measurement technique. Radiography can be adjunct when indicated. Calcium and vitamin D nutritional supplementation should be at currently recommended levels. Patients should be counselled in fall-avoidance techniques and exercises. Immobilization should be avoided. Guidelines for management of acute pain are listed. Ovarian hormone therapy is the therapy of choice for osteoporosis prevention and treatment in postmenopausal women. Bisphosphonates are an alternative therapy for women with established osteoporosis who cannot or prefer not to take ovarian hormone therapy.

A prospective cohort study of intake of calcium, vitamin D, and other micronutrients in relation to incidence of rectal cancer among postmenopausal women.

Cancer Epidemiol Biomarkers Prev, 7(3):221-5 1998 Mar

To investigate whether high intakes of calcium and other micronutrients (carotene, retinol, and vitamins C, D, and E) are related to reduced risks of rectal cancer, we analyzed data from a large cohort study of postmenopausal Iowa women who responded to a mailed survey in 1986. After 9 years of follow-up, 144 incident rectal cancer cases were ascertained among the 34,702 women at risk. Intake levels of micronutrients at baseline were derived from self-reported data on vitamin supplements and dietary intake of 127 foods included in a semiquantitative food frequency questionnaire. After adjustment for total energy intake and other potential confounding factors, a dose-response inverse association was observed between total calcium intake and the risk of rectal cancer: adjusted relative risks (RRs) were 1.00, 0.90, and 0.59 (trend test, P = 0.02) from the lowest to the highest calcium intake tertiles. High intakes of dietary and supplement calcium were both related to a slightly reduced risk of rectal cancer, but neither of the trend tests was statistically significant. Reduced risks of rectal cancer were also observed for high intake of carotene and vitamins A, C, and D, although none of the associations were statistically significant. For vitamin D, the adjusted RRs were 1.00, 0.71, and 0.76 (trend test, P = 0.20) for increasing intake tertiles. Compared with women who consumed low levels of both total calcium and vitamin D, those in the highest intake group of both nutrients were at a 45% reduced risk of rectal cancer (RR, 0.55; 95% confidence interval, 0.32-0.93). This study supports the hypothesis that high intake of calcium and possibly other micronutrients may be beneficial in the prevention of rectal cancer.

An overview of the adverse reactions to adrenal corticosteroids.

Adverse Drug React Toxicol Rev, 53(4):203-6 1996 Nov

Glucocorticoids are amongst the most potent immunosuppressant drugs available and are widely used in many inflammatory and autoimmune conditions such as asthma and systemic lupus erythematosus. These agents are, however, associated with potentially substantial systemic side effects including electrolyte disturbances, cardiovascular effects, diabetes mellitus and loss of bone density and osteoporosis with concomitant vertebral fracture. The clinical utility of these agents should be tempered by the use of a minimum effective dose and, where possible, by the administration of alternate daily or pulse steroids which may have some impact on reducing the prevalence of these adverse effects. Moreover, recent evidence suggests that calcium and vitamin D co-administration may offset the chronic effects of glucocorticoids in inducing bone loss. A greater understanding of the molecular and cellular basis of glucocorticoid action, particularly as it relates to bone loss, is necessary to optimize efficacy and safety and to utilize therapies which may minimize the long-term effects of glucocorticoids. Furthermore, there is a need to develop newer glucocorticoids which have lesser effects on bone and other sites of adverse events, whilst retaining their immunosuppressive and anti-inflammatory action.

Osteoporosis: detection, prevention, and treatment in primary care.

Geriatrics, 53(8):22-3, 27-8, 33 passim 1998 Aug

Osteoporosis is a silent disease that often remains asymptomatic and undetected until bone fracture occurs. Because of the high morbidity associated with fracture, prevention is a clinical priority. In order to identify those who would benefit from therapeutic intervention, bone density measurement is indicated in patients with risk factors for osteoporosis. Therapies include hormone replacement, calcitonin, bisphosphonates, and selective estrogen receptor modulators, as well as exercise and supplements of calcium and vitamin D. The goal of all treatments is to decrease the risk of fracture by minimizing bone loss and increasing bone mass.