A highly polymorphic microsatellite within intron 5 of the porcine 54/56 kDa vacuolar H(+)-ATPase subunit gene (V-ATPase)

OBJECTIVE: To assess the validity of a short calcium food frequency questionnaire (FFQ) for use in young children. DESIGN: Calcium intake from an estimated 4 d diet record (4DDR) was compared with the calcium intake from a 35 item FFQ specifically designed to assess habitual calcium intake and previously validated for adult women. SUBJECTS: Forty-one girls and 26 boys aged 3-6 y recruited by advertisement for studies of nutrition and bone health. RESULTS: Mean (s.d.) calcium intakes were 798 mg (271) and 942 mg (419) for the 4DDR and FFQ respectively, (r = 0.52). Mean difference (s.d. of difference) in calcium intake between the two methods was 144 mg (355), showing that the FFQ may estimate calcium intakes 565 mg below to 854 mg above diet record values. 84% of subjects when classified by the 4DDR fell into the same or adjacent quartiles when classified by the FFQ. Only two subjects were classified in extreme quartiles for the two methods. The FFQ correctly identified 68% of children with recorded intakes less than 800 mg. CONCLUSIONS: The short calcium FFQ tended to overestimate actual calcium intakes in young children, and would not be appropriate for determining calcium intake of individuals. However, the FFQ demonstrated good ability to classify subjects into extremes of calcium intake. Moreover, the predictive value of the FFQ in identifying children with intakes below the current recommended intake of 800 mg was reasonably high (79%).     

Biochemical effects of calcium supplementation in postmenopausal women: influence of dietary calcium intake

We studied the biochemical effects of calcium supplementation during a 2-mo course in postmenopausal women (x +/- SD: 64 +/- 5 y of age and 14.5 +/- 6.7 y since menopause). The effects on calcium homeostasis and bone remodeling were assessed after 1 and 2 mo of daily administration of either calcium carbonate (1200 mg elemental Ca/d, n = 60) or a placebo (n = 56). The daily dietary calcium intake assessed before the beginning of calcium supplementation was 786 mg/d. We found a significant inverse relation between baseline intact parathyroid hormone (iPTH) and dietary calcium intake before supplementation (r = -0.48, P = 0.0002). A significant increase in urinary excretion of pyridinoline was observed when the dietary calcium intake was lower than the median value. Calcium supplementation resulted in a significant increase in 24-h urinary calcium (39%, P < 0.02) and a significant reduction of bone alkaline phosphatase at 2 mo and of all bone-resorption markers (hydroxyproline, pyridinoline, and deoxypyridinoline) at I and 2 mo without significant changes in 44-68 PTH fragments or iPTH concentrations. When the dietary calcium intake was low (mean +/- SD: 576 +/- 142 mg/d), calcium supplementation was responsible for a greater increase in urinary calcium excretion and a greater decrease in markers of bone turnover. The greatest variations were observed for deoxypyridinoline at 1 and 2 mo (-18.5%, P < 0.05) and for pyridinoline at 1 mo (-16.3%, P < 0.01). Two months of calcium supplementation in postmenopausal women was efficient in reducing markers of bone turnover, with a greater effect in women with a low dietary calcium intake.     

Urinary calcium, sodium, and bone mass of young females

Calcium is an important determinant of peak bone mass in young adults because of its influence on skeletal development during growth. Attainment of maximum peak bone mass requires optimal positive balance between calcium intake and obligatory losses of calcium, primarily in urine and feces. Urinary excretion is an important determinant of calcium retention in the body. Accordingly, the purpose of this study was to evaluate the influence of various nutrients on urinary calcium excretion, and to assess their impact on bone mass of young females, aged 8-13 y, during early puberty. The study was conducted in 381 healthy white females in pubertal stage 2. From each participant we collected basic anthropometric measurements, a 3-d food record, blood, a 24-h urine sample, and bone mass measurements of the total body and forearm by dual X-ray absorptiometry. Urinary sodium was found to be one of the most important determinants of urinary calcium excretion: [urinary calcium (mmol/d) = 0.01154 x urinary sodium (mmol/d) + 0.823], whereas calcium intake had relatively little impact: [urinary calcium (mmol/d) = 0.02252 x calcium intake (mmol/d) + 1.5261]. Urinary calcium was much higher at a calcium intake of approximately 37.5 mmol/d (1500 mg/d), supporting the notion that calcium is a threshold nutrient. Calcium intake had a significant positive influence on the bone mineral content and density of the whole body and radius shaft whereas urinary calcium had a negative influence, presumably by reducing calcium accretion into the skeleton.(ABSTRACT TRUNCATED AT 250 WORDS)     

Twenty-four-hour L-[1-(13)C]tyrosine and L-[3,3-(2)H2]phenylalanine oral tracer studies at generous, intermediate, and low phenylalanine intakes to estimate aromatic amino acid requirements in adults

Daily pattern and rates of whole-body tyrosine oxidation and phenylalanine hydroxylation were determined in young adults (15 men, 1 woman) receiving [13C]tyrosine and [(2)H2]phenylalanine via primed, constant oral infusion and [(2)H4]tyrosine by vein (five subjects also received [(2)H3]leucine simultaneously by vein) continuously for 24 h (12 h fast then 12 h fed). Subjects were given a diet supplying 96.6 (n = 5), 35.6 (the proposed requirement; n = 5), and 18.5 mg phenylalanine x kg(-1) x d(-1) (n = 6) based on an otherwise adequate L-amino acid mixture for 6 d before the 24-h tracer study began. [Each diet was low in tyrosine: 6.79 mg x kg(-1) x d(-1).] Our hypothesis was that subjects would be in tyrosine equilibrium, positive balance, or both, at the 96.6- and 35.6-mg intakes and in distinctly negative balance at the 18.5-mg intake. The diurnal pattern in phenylalanine and tyrosine kinetics was dependent on the intake and, presumably, on the adequacy of dietary phenylalanine. Wholebody tyrosine balances, determined from rates of phenylalanine hydroxylation and tyrosine input and oxidation were negative (0.05 < P < 0.1 from zero balance) with the low (18.5 mg) phenylalanine intake [total aromatic amino acid (AAA) intake: 25.3 mg x kg(-1) x d(-1)] but at equilibrium (P > 0.05 from zero balance) with the two higher phenylalanine intakes. Whole-body AAA balance (AAA intake - tyrosine oxidation) was negative (P < 0.05 from zero balance) with the low intake, at equilibrium with the intermediate intake, and apparently distinctly positive (P < 0.05) with the generous intake. Despite model limitations, as discussed, these findings lend further support for a proposed, tentative value for a total mean requirement of 39 mg AAA x kg(-1) x d(-1).     

Calcium and magnesium balance in 9-14-y-old children

Few data are available regarding calcium and magnesium absorption and endogenous fecal excretion in children. We used a multitracer stable isotope technique to assess calcium and magnesium balance in 12 boys and 13 girls aged 9-14 y (mean weight: 42 kg) maintained on relatively high calcium intakes (mean: 1310 +/- 82 mg/d). There were no significant differences in absorption of calcium or magnesium from milk between boys and girls. Calcium retention (balance) correlated positively with calcidiol (25-hydroxyvitamin D) concentration (r = 0.48, P = 0.02) and serum alkaline phosphatase activity (r = 0.44, P = 0.03). There was no significant relation between magnesium balance and concentration. When data from this study were combined with our previously reported data, an increase in total calcium absorption was seen for pubertal (Tanner stages 2-4) but not prepubertal (Tanner stage 1) white children over the range of intakes from approximately 750 to 1350 mg/d. Despite intakes similar to the 1989 recommended dietary allowance for magnesium (mean intake: 6.4 +/- 1.2 mg.kg-1.d-1), 11 of the 25 subjects (6 girls and 5 boys) were in negative magnesium balance. We conclude that benefits from higher calcium intakes, < or = 1350 mg/d, were most apparent in pubertal children. In addiction, higher magnesium intakes should be considered for children.     

Evidence that increased calcium intake does not prevent early postmenopausal bone loss

Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose baseline calcium intake was <500 mg/d were advised to increase their calcium intake. Mean (+/- SE) BMD decreased by 1.9% +/- 0.16% at the lumbar spine and 1.6% +/- 0.14% at the hip over the 24-month period. Despite wide variations in baseline calcium intake and changes in calcium intake, these measures were not significantly associated with changes in BMD or bone turnover. Even women whose total calcium intake was >1333 mg/d (the highest tertile of total calcium intake) showed a decline in BMD of almost 2%, similar to declines in the lower two tertiles of total calcium intake (<869 and 869-1333 mg/d, respectively). Increased calcium intake resulted in modest mean increases of approximately 200 mg/d. We were unable to demonstrate that increases of this magnitude or much greater (1 g/d) were protective against declines in BMD at any site, even in women who had the lowest calcium intake at baseline. In addition to adequate calcium intake, more effective therapy appears to be required when the therapeutic goal is to increase or maintain BMD.     

Iron status, menarche, and calcium supplementation in adolescent girls

The effects of growth, menstrual status, and calcium supplementation on iron status were studied over 4 y in 354 girls in pubertal stage 2 who were premenarcheal at baseline (x+/-SD age: 10.8+/-0.8 y). Girls were randomly assigned to placebo or treatment with 1000 mg Ca/d as calcium citrate malate. Anthropometric characteristics, bone mass, and nutritional status were measured biannually; ferritin was measured annually; and red blood cell indexes were determined at 4 y. The simultaneous effects of iron intake and menstrual status on serum ferritin, after change in lean body mass (LBM) was controlled for, were evaluated in subjects in the upper and lower quartiles of cumulative iron intake. The average maximal accumulation of LBM (386 g/mo; 95% CI: 372, 399) occurred 0.5 y before the onset of menarche. Change in LBM was a significant predictor of serum ferritin (P < 0.0001), with a negative influence on iron status (t ratio=-4.12). The 2 fitted mathematical models representing ferritin concentrations of subjects in the upper and lower quartiles of cumulative iron intake were significantly different (P < 0.018). The regression line of the ferritin concentration in menstruating girls with high iron intakes had a less negative slope than the line fit to serum ferritin concentrations in girls with low iron intakes (NS). Serum ferritin concentrations at 0, 1, 2, 3, and 4 y were not significantly different between groups. In addition, there was no significant difference between groups in any of the red blood cell indexes. In summary, growth spurt and menstrual status had adverse effects on iron stores in adolescent girls with low iron intakes (<9 mg/d), whereas long-term supplementation with calcium (total intake: approximately 1500 mg/d) did not affect iron status.     

Use of peripheral quantitative computed tomography for densitometry of the femoral neck and spine in cynomolgus monkeys (Macaca fascicularis)

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.     

Calcium supplementation and bone mineral density in adolescent girls

OBJECTIVE: To evaluate the effect of calcium supplementation on bone acquisition in adolescent white girls. DESIGN: A randomized, double-blind, placebo-controlled trial of the effect of 18 months of calcium supplementation on bone density and bone mass. SUBJECTS: Ninety-four girls with a mean age of 11.9 + 0.5 years at study entry. SETTING: University hospital in a small town. INTERVENTIONS: Calcium supplementation, 500 mg/d calcium as calcium citrate malate; controls received placebo pills. MAIN OUTCOME MEASURES: Bone mineral density and bone mineral content of the lumbar spine and total body were measured by dual-energy x-ray absorptiometry and calcium excretion from 24-hour urine specimens. RESULTS: Calcium intake from dietary sources averaged 960 mg/d for the entire study group. The supplemented group received, on average, an additional 354 mg/d of calcium. The supplemented group compared with the placebo group had greater increases of lumbar spine bone density (18.7% vs 15.8%; P = .03), lumbar spine bone mineral content (39.4% vs 34.7%; P = .06), total body bone mineral density (9.6% vs 8.3%; P = .05), and 24-hour urinary calcium excretion (90.4 vs 72.9 mg/d; P = .02), respectively. CONCLUSIONS: Increasing daily calcium intake from 80% of the recommended daily allowance to 110% via supplementation with calcium citrate malate resulted in significant increases in total body and spinal bone density in adolescent girls. The increase of 24 g of bone gain per year among the supplemented group translates to an additional 1.3% skeletal mass per year during adolescent growth, which may provide protection against future osteoporotic fracture.     

Zinc balance in adolescent females consuming a low- or high-calcium diet

There is increasing evidence that calcium intake up to the threshold amount (1480 mg/d) increases bone mass during growth. However, there is concern that such a high calcium intake may interfere with the utilization of other nutrients such as zinc, which is also important for skeletal development. The purpose of our study was to investigate the effect of long-term calcium supplementation on zinc utilization in 26 adolescent females (mean +/- SD age 11.3 +/- 0.5 y) during a 14-d period. Each day subjects consumed a metabolic diet containing 722 mg Ca and 6.3 mg Zn. Participants were randomly assigned to receive either a placebo or a calcium supplement containing 1000 mg supplemental Ca/d as calcium citrate malate. Supplementation began 15 wk before the balance period to allow for adaptation to the greater calcium intake. Mean (+/-SD) zinc balance (0.8 +/- 0.8 compared with 0.3 +/- 1.1 mg/d, P = 0.23), fecal zinc (4.3 +/- 0.6 compared with 4.7 +/- 1.4 mg/d, P = 0.27), urinary zinc (0.4 +/- 0.2 compared with 0.5 +/- 0.1 mg/d, P = 0.55), and net zinc absorption (21% compared with 15%, P = 0.33) were not significantly different between the high- and low-calcium groups. Our results suggest that increasing the recommended dietary allowance of calcium to 1500 mg/d as recommended by the National Institutes of Health consensus panel will not have adverse effects on zinc utilization in adolescent females.     

Effect of measuring bone mineral density on calcium intake

The diet in Japan has improved, but calcium intake has not increased for the past ten years, and it remains insufficient. To prevent osteoporosis, instruction in nutrition is directed at increasing calcium intake. We studied the effect of measuring bone mineral density on calcium intake in people receiving nutrition education. Intake of other nutrients was also measured. The subjects were 87 healthy women living in an agricultural region (Yamanashi Prefecture). They were members of a group formed to improve the diet of people in their area. For three days in October 1992 and in August 1994 food-weight records were obtained. A total of 76 of the 87 women chose to have their bone mineral density measured. The measurements before the first nutrition assessment in 1992. The intake of almost all nutrients tended to be greater in 1994 than in 1992. Calcium intake exceeded the minimum daily requirement (600mg). Calcium intake increased between 1992 and 1994 only in the subjects whose bone mineral density had been measured. Calcium intake decreased in the other subjects. Therefore, nutrition education programs aimed at preventing osteoporosis may be more effective if bone mineral density is measured. In addition, an appropriate balance of other nutrients can be maintained as the intake of calcium is increased.     

The (-)-enantiomer of gossypol inhibits proliferation of stromal cells derived from human breast adipose tissues by enhancing transforming growth factor beta1 production

BACKGROUND: Age-related osteoporosis may be associated with inefficient intestinal calcium absorption and bone remodeling. OBJECTIVE: We investigated the pathogenesis of age-related osteoporosis in Chinese women with habitual low calcium intakes. DESIGN: We studied the response of intestinal calcium absorption, calcitropic hormones, and biochemical bone markers to graded dietary calcium deprivation. RESULTS: The osteoporotic subjects (n = 25) had higher urinary calcium excretion (P < 0.05) and lower plasma 1,25-dihydroxyvitamin D concentrations (P < 0.02) than did age-matched control women (n = 25). Parathyroid hormone was not significantly different from that in age-matched control women but was significantly higher than in young women (n = 15, P < 0.05). Fractional 45Ca absorption was approximately 61% in all 3 groups when the diet was unmodified and increased to 71%, 69%, and 68% in the osteoporotic subjects, age-matched control women, and young women, respectively, when dietary calcium was reduced to 300 mg/d. When the osteoporotic women were calcium deprived, serum 1,25-dihydroxyvitamin D failed to increase but urinary calcium excretion persisted. In contrast, supplementation with 1200 mg Ca resulted in a lowering of parathyroid hormone (P < 0.005 compared with the unmodified diet) and 1,25-dihydroxyvitamin D (P < 0.01) and decreased fractional 45Ca absorption (P < 0.01), suggesting that the increased calcium intake was associated with a potent compensatory ability of the intestine and calcitropic hormones to adapt. Calcium supplementation lowered osteocalcin (P < 0.05) but not alkaline phosphatase, which remained elevated in the osteoporotic subjects at all stages. CONCLUSIONS: Elderly osteoporotic women had reduced 1,25-dihydroxyvitamin D production, excessive urinary calcium loss, and high bone turnover. The Chinese women had exceptionally potent intestinal calcium absorption.     

Determinants of bone mass in Chinese women aged 21-40 years. II. Pattern of dietary calcium intake and association with bone mineral density

A study on the determinants of bone mass in young women is being carried out among 287 young Chinese women aged 21-40 years. The baseline cross-sectional data show that the mean dietary calcium intake, estimated from the quantitative food frequency method, was 448 mg/day (standard deviation = 219). About 50% of the calcium source was from vegetables and 22% from dairy products. Among women aged 21-30 years, those with a dietary calcium intake of at least 600 mg/day had a 4%-7% higher mean bone mineral density at the spine and femur when compared with those with a mean intake below 300 mg/day. In women aged 31-40 years, subjects belonging to the highest quartile of calcium density (> or = 35 mg/420 kJ) had a 3%-8% higher mean bone mineral density at the spine and femur when compared with those in the lowest quartile (< 20.8 mg/420 kJ). Favorable calcium intake is beneficial in this population of young women with habitual low dietary calcium intake.     

Dietary practices and lipid intake in relation to plasma lipid profile in Hong Kong Chinese

OBJECTIVE: To study dietary lipid intake and plasma lipid profile of the Hong Kong Chinese population as part of a territory wide survey on cardiovascular risk factors. DESIGN: Randomised age and sex stratified survey. SUBJECTS: 1010 subjects aged 25-74 y (500 men, 510 women). MEASUREMENTS: A food frequency method with food tables compiled for Hong Kong was used for nutrient quantitation, while a separate questionnaire was used to examine dietary practices. Plasma lipid profile was estimated using standard laboratory methods. RESULTS: Total calorie, fat, saturated fatty acid (SFA), poly- and mono-unsaturated fatty acid (PUFA and MUFA), and cholesterol intake were higher in men; however when adjusted for caloric intake no difference was observed. Men had lower intake of PUFA as percentage of total energy had a higher Hegsted Score compared with women. Subjects consuming beans twice or more per week had lower total cholesterol and LDL-cholesterol concentrations. Overall, the population dietary intake was close to the ideal for cardiovascular health: percentage fat not greater than 30% of the total calorie intake, saturated fat intake not greater than 10% of calories, and cholesterol less than 180 mg/1000 Kcal. CONCLUSION: The dietary pattern for Hong Kong Chinese appear to be satisfactory with respect to cardiovascular health.     

A randomized, placebo-controlled trial of calcium supplementation for decreased bone density in corticosteroid-using patients with inflammatory bowel disease: a pilot study

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high prevalence of osteoporosis. A number of studies have found that corticosteroid use is associated with the development of osteoporosis in these patients. Calcium supplementation may be of benefit in corticosteroid-induced osteoporosis and calcium may be a nutrient that patients with IBD lack. AIM: To test the benefit of calcium supplementation on bone density in a pilot study over a 1-year period, in a group of corticosteroid-using patients with IBD, in a randomized, double-blind, placebo-controlled treatment study. METHODS: Corticosteroid-using patients with IBD including males over the age of 18 years and premenopausal females, were randomized to receive either calcium carbonate 1000 mg plus vitamin D 250 IU (Oscal) or an identically matched placebo. Dual energy X-ray absorptiometry measurements of bone density were obtained at entry and at 1 year. At entry, and every 3 months thereafter, serum was collected for the measurement of haemoglobin, biochemistry and bone hormones. Simultaneously a 24-h urine collection was analysed for calcium excretion and creatinine clearance, and a 4-day food record was collected to document dietary calcium and vitamin D ingestion. RESULTS: We found a high prevalence of moderately severe decreased bone density in corticosteroid-using patients with IBD. The dose of prednisone in the year prior to study entry was inversely correlated with bone density at the hip (R = -0.67, P = 0.004). At study entry serum osteocalcin was inversely correlated with corticosteroid dose in the year prior to the study (R = -0.64, P = 0.02) and at study end, directly correlated with the percentage change in spine bone density (R = 0.59, P = 0.01). The dietary calcium intake of these patients was close to the current RDA (recommended daily intake) for premenopausal, post-adolescent adults. Calcium supplementation with small extra doses of vitamin D conferred no obvious benefit to bone density at the end of 1 year. There was no correlation between oral calcium ingestion and bone mass measurements. Both the treatment and placebo groups' bone density remained relatively stable at 1 year, suggesting that bone loss in corticosteroid-using patients may peak early into the use of the corticosteroids. CONCLUSIONS: Calcium supplementation (1000 mg/day) conferred no significant benefit to bone density at 1 year in patients with corticosteroid-using IBD patients with osteoporosis. Future investigations should explore other therapeutic avenues that may have greater effects on increasing bone density in patients who already have considerable osteoporosis.     

Age-related decreases in insulin-like growth factor-I and transforming growth factor-beta in femoral cortical bone from both men and women: implications for bone loss with aging

We determined the skeletal content of insulin-like growth factor-I (IGF-I) and transforming growth factor-beta (TGF beta) in human bone as a function of age, using 66 samples of femoral cortical bone obtained from 46 men and 20 women between the ages of 20-64 yr. We found a linear decline in the skeletal content of IGF-I (nanograms per mg protein) with donor age (r = -0.43; P < 0.001) in the total population. The skeletal content of TGF beta also decreased with age (i.e. 1/TGF beta vs. age; r = 0.28; P < 0.02) for the total population. We did not observe any difference in the skeletal growth factor content between male and female donors. IGF-I content, when analyzed by decade divisions of age, showed a reduction between the 20- to 29-yr-old and the 50- to 59-yr-old subjects (P < 0.02). The loss rate of IGF-I was 1.56 ng/mg protein.yr, corresponding to a net loss of 60% of skeletal IGF-I between the ages of 20-60 yr. The loss rate of TGF beta was 0.03 ng/mg protein.yr, corresponding to a net loss of 25% of the skeletal TGF beta between the ages of 20-60 yr.     

Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized placebo-controlled trial

Elderly women are at increased risk for bone loss and fractures. In previous cross-sectional and longitudinal studies of women residing in northern latitudes, bone loss was most pronounced during winter months and in those consuming less than 1 g calcium per day. In this study we sought to test the hypothesis that calcium supplementation by either calcium carbonate or dietary means would prevent seasonal bone loss and preserve bone mass. Sixty older postmenopausal women without osteoporosis were randomized to one of three treatment arms: Dietary milk supplementation (D-4 glasses of milk/day), Calcium carbonate (CaCO3-1000 mg/day in two divided doses), or placebo (P). After 2 yr, placebo-treated women consumed a mean of 683 mg/day of calcium and lost 3.0% of their greater trochanteric (GT) bone mineral density (BMD) (P < 0.03 vs. baseline); Dietary supplemented women averaged a calcium intake of 1028 mg/day and sustained minimal loss from the GT (-1.5%; P = 0.30), whereas CaCO3-treated women (total Ca intake, 1633 mg/day) suffered no bone loss from the GT and showed a significant increase in spinal and femoral neck BMD (P < 0.05). Femoral bone loss occurred exclusively during the two winters of the study (i.e. total loss, -3.2%; P < 0.02 in placebo-treated women) with virtually no change in GT BMD during summer. Serum 25-OH vitamin D declined by more than 20% (P < 0.001) in all groups during the winter months but returned to baseline in summer; PTH levels rose approximately 20% (P < 0.001) during winter but did not return to baseline during the summers. Urine N-telopeptide and osteocalcin levels increased significantly but only in the P-treated women and only during winter. Serum insulin growth factor binding protein 4, an inhibitory insulin growth factor binding protein, rose 15% (P < 0.03) from summer to winter, but this increase was significant only in those women consuming <1000 mg/day of calcium. By multivariate analysis, total calcium intake was the strongest predictor of bone loss from the hip. Urinary N-telopeptide also closely correlated with GT BMD but only during winter (P = 0.003). We conclude that calcium supplementation prevents bone loss in elderly women by suppressing bone turnover during the winter when serum 25-OH vitamin D declines and serum PTH increases. The precise amount of calcium necessary to preserve BMD in elderly women requires further studies, although in this study, at least 1000 mg/day of supplemental calcium was adequate prophylaxis against femoral bone loss.     

A randomized trial of sevelamer hydrochloride (RenaGel) with and without supplemental calcium. Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients

OBJECTIVE: We have previously shown sevelamer hydrochloride (RenaGel) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients. PATIENTS AND METHODS: We performed a randomized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium, using the serum phosphorus concentration and intact parathyroid hormone (PTH) as the principal outcomes of interest. Calcium (900 mg elemental) was provided as a once-nightly dose on an empty stomach. 71 patients were randomized and included in the intent-to-treat population; 55 completed the 16-week study period (2 weeks washout, 12 weeks treatment, 2 weeks washout). 49% of subjects were taking vitamin D metabolites. RESULTS: Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods. RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus (mean change -2.4 mg/dL vs. -2.3 mg/dL). RenaGel with calcium was associated with a small increase in serum calcium (mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group, P = 0.09) that was not statistically significant. During the treatment phase, the reduction in PTH tended to be greater in the RenaGel with calcium group (median change -67.0 vs. -22.5 pg/mL in RenaGel group, P = 0.07). Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH (median change -114.5 vs. -22 pg/mL in RenaGel group, P = 0.006). Adverse events were seen with equal frequency in both groups, being generally mild in intensity, and rarely attributable to the drugs. CONCLUSION: We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD-related hyperphosphatemia. Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism.     

Health care coverage and access for children in an urban state: the New York perspective

To clarify the role of the intestine, kidney, and bone in maintaining calcium homeostasis during pregnancy and lactation and after the resumption of menses, a longitudinal comparison was undertaken of 14 well-nourished women consuming approximately 1200 mg Ca/d. Measurements were made before conception (prepregnancy), once during each trimester of pregnancy (T1, T2, and T3), early in lactation at 2 mo postpartum (EL), and 5 mo after resumption of menses. Intestinal calcium absorption was determined from the enrichment of the first 24-h urine sample collected after administration of stable calcium isotopes. Bone mineral of the total body and lumbar spine was measured by dual-energy X-ray absorptiometry and quantitative computerized tomography, respectively. Twenty-four-hour urine and fasting serum samples were analyzed for calcium, calcitropic hormones, and biochemical markers of bone turnover. Despite an increase in calcium intake during pregnancy, true percentage absorption of calcium increased from 32.9+/-9.1% at prepregnancy to 49.9+/-10.2% at T2 and 53.8+/-11.3% at T3 (P < 0.001). Urinary calcium increased from 4.32+/-2.20 mmol/d at prepregnancy to 6.21+/-3.72 mmol/d at T3 (P < 0.001), but only minor changes in maternal bone mineral were detected. At EL, dietary calcium and calcium absorption were not significantly different from that at prepregnancy, but urinary calcium decreased to 1.87+/-1.22 mmol/d (P < 0.001) and trabecular bone mineral density of the spine decreased to 147.7+/-21.2 mg/cm3 from 162.9+/-25.0 mg/cm3 at prepregnancy (P < 0.001). Calcium absorption postmenses increased nonsignificantly to 36.0+/-8.1% whereas urinary calcium decreased to 2.72+/-1.52 mmol/d (P < 0.001). We concluded that fetal calcium demand was met by increased maternal intestinal absorption; early breast-milk calcium was provided by maternal renal calcium conservation and loss of spinal trabecular bone, a loss that was recovered postmenses.     

Bone density and cyclic ovarian function in trained runners and active controls

This study was conducted to determine whether rigorous exercise training adversely affects ovarian hormone levels and bone health in cyclically menstruating trained runners. Ovarian hormones, bone mineral density (BMD), body composition, 3-d diet records, 3-d estimated energy expenditure, and menstrual histories were evaluated in 10 trained collegiate runners and 10 moderately active controls. The trained runners had lower total body calcium per kg of soft lean tissue measured by DEXA (P = 0.045). Half of the trained runners had experienced stress fractures compared with only one of the moderately active controls. The trained runners' lumbar (L2-L4) BMD (1.178 g.cm-2) was not significantly different from that of the active controls (1.283 g.cm-2) (P = 0.074) but, for all subjects combined, there wasa significant inverse relation between L2-L4 BMD and distance run per week (P = 0.036). Further, adding age, body weight, percent body fat, daily energy intake, and daily calcium intake to a stepwise multiple regression analysis did not significantly improve predictive precision. The trained runners consumed nearly twice the amount of calcium (1089 mg.d-1 vs 641 mg.d-1, respectively; P = 0.036), while intake of other nutrients did not differ significantly between groups. Urinary estrone conjugates (E1C) were lower in the trained runners during the early follicular phase (P = 0.028), while pregnanediol-3-glucuronide (PdG) was not significantly different between groups during the luteal phase (P = 0.213). Thus, it appears that lower estrogen production, especially during the early follicular phase, and not progesterone, is associated with lower whole body calcium per kg of soft lean tissue and, probably, L2-L4 BMD. Results of this study also suggest that regular menstrual cycles do not imply normal ovarian hormone function in young women who are engaged in either recreational or competitive running.