Cumulative effects of calcium supplementation and physical activity on bone accretion in premenarchal children: a double-blind randomised placebo-controlled trial. A follow-up study on the effects of calcium-supplement withdrawal and puberty on bone acquisition of children. The effect of calcium supplementation on bone density in premenarcheal females: a co-twin approach. Regional specificity of exercise and calcium during skeletal growth in girls: a randomized controlled trial. Bone mineral contents and plasma osteocalcin concentrations of Gambian children 12 and 24 mo after the withdrawal of a calcium supplement. A co-twin study of the effect of calcium supplementation on bone density during adolescence. Randomized trial of physical activity and calcium supplementation on bone mineral content in 3- to 5-year-old children. Bone mineral acquisition in low calcium intake children following the withdrawal of calcium supplement. Effect of a calcium and exercise intervention on the bone mineral status of 16-18-y-old adolescent girls. Calcium supplementation and bone mineral density in adolescent girls. Sustained effect of short-term calcium supplementation on bone mass in adolescent girls with low calcium intake. Effect of habitual dietary calcium intake on calcium supplementation in 12-14-y-old girls. Skeletal site selectivity in the effects of calcium supplementation on areal bone mineral density gain: a randomized, double-blind, placebo-controlled trial in prepubertal boys.
High calcium intake combined with physical activity during childhood have been shown to improve bone mass accrual and bone mineral density. Our aim was to study the combined effect of calcium and exercise on bone gain in children. Two milk-powder products containing either 800 mg of calcium phosphate (calcium) or not (placebo) were randomly allocated to 113 healthy premenarchal girls on a daily basis for 1 year. The group was composed of 63 exercise (7.2 +/- 4 hours of exercise/week) and 50 sedentary (1.2 +/- 0.8 hours of exercise/week) children. The final experiment had 4 groups: exercise/calcium (n = 12), exercise/placebo (n = 42), sedentary/calcium (n = 10), and sedentary/placebo (n = 21). Bone mineral density (BMD) at 6 skeletal sites and body composition were determined by DXA. Bone age was calculated and the daily spontaneous calcium intake was assessed by a frequency questionnaire. All the tests were performed at baseline and 1 year by the same observer. BMD gains were significantly greater in the exercise/calcium group than in other groups at the total body (increase of 6.3 %, p < 0.05), lumbar spine (11 %, p < 0.05), femoral neck (8.2 %, p < 0.02), and Ward's triangle (9.3 %, p < 0.01). There was no difference between the other groups. These data suggest that calcium supplementation increases the effect of physical exercise on bone mineral acquisition in the period preceding puberty, and that calcium supplementation without physical activity does not improve the BMD acquisition during this period. Physical exercise that stimulates bone accretion needs a high calcium intake to be completely effective. Recent calcium supplementation trials in children have confirmed a positive but moderate effect of calcium intake on bone mineral accretion. However, the lasting effect of a higher bone mineral mass after calcium-supplement withdrawal is not known. This is an 18-mo follow-up study conducted after an 18-mo controlled calcium supplementation trial to study the persistent effect of higher bone mineral mass in children. Radial bone mineral mass was determined by single-photon absorptiometry; lumbar spine and femoral neck bone mineral mass were evaluated by dual-energy X-ray absorptiometry in 84 healthy Hong Kong children at age 8.5 y and these evaluations were repeated at age 10 y. Pubertal status was determined by Tanner staging. At the end of the follow-up, the differences in percentage gains in lumbar spine bone mineral content (12.1 +/- 8.2% compared with 14.9 +/- 10.05%, P = 0.24) and lumbar spine area (8.6 +/- 5.1% compared with 9.4 +/- 5.5%, P = 0.47) between the study and control groups disappeared. Dietary calcium intakes during follow-up were similar for the two groups (555 and 640 mg/d, P = 0.23). In multiple-regression analyses, pubertal status was the strongest correlate of bone acquisition and linear growth in the study period. In conclusion, higher percentage gains in bone mineral mass in childhood by calcium supplementation for 18 mo were reversible. Our study showed that the benefits of calcium supplementation disappear after treatment is withdrawn. Longer-term calcium trials are necessary to determine whether peak bone mass can be modified through sustained supplementation so that appropriate calcium intakes can be determined. The age and developmental stage at which calcium supplementation produces the greatest bone effects remain controversial. We tested the hypothesis that calcium supplementation may improve bone accrual in premenarcheal females. Fifty-one pairs of premenarcheal female twins (27 monozygotic and 24 dizygotic; mean +/- sd age, 10.3 +/- 1.5 yr) participated in a randomized, single-blind, placebo-controlled trial with one twin of each pair receiving a 1200-mg calcium carbonate (Caltrate) supplement. Areal bone mineral density (aBMD) was measured at baseline and 6, 12, 18 and 24 months. There were no within-pair differences in height, weight, or calcium intake at baseline. Calcium supplementation was associated (P < 0.05) with increased aBMD compared with placebo, adjusted for age, height, and weight at the following time points from baseline: total hip, 6 months (1.9%), 12 months (1.6%), and 18 months (2.4%); lumbar spine, 12 months (1.0%); femoral neck, 6 months (1.9%). Adjusted total body bone mineral content was higher in the calcium group at 6 months (2.0%), 12 months (2.5%), 18 months (4.6%), and 24 months (3.7%), respectively (all P < 0.001). Calcium supplementation was effective in increasing aBMD at regional sites over the first 12-18 months, but these gains were not maintained to 24 months. Combining exercise with calcium supplementation may produce additive or multiplicative effects at loaded sites; thus, we conducted a single blind, prospective, randomized controlled study in pre- and early-pubertal girls to test the following hypotheses. (1) At the loaded sites, exercise and calcium will produce greater benefits than exercise or calcium alone. (2) At non-loaded sites, exercise will have no benefit, whereas calcium with or without exercise will increase bone mass over that in exercise alone or no intervention. Sixty-six girls aged 8.8 +/- 0.1 years were randomly assigned to one of four study groups: moderate-impact exercise with or without calcium or low-impact exercise with or without calcium. All participants exercised for 20 minutes, three times a week and received Ca-fortified (434 +/- 19 mg/day) or non-fortified foods for 8.5 months. Analysis of covariance (ANCOVA) was used to determine interaction and main effects for exercise and calcium on bone mass after adjusting for baseline bone mineral content and growth in limb lengths. An exercise-calcium interaction was detected at the femur (7.1%, p < 0.05). In contrast, there was no exercise-calcium interaction detected at the tibia-fibula; however, there was a main effect of exercise: bone mineral content increased 3% more in the exercise than non-exercise groups (p < 0.05). Bone mineral content increased 2-4% more in the calcium-supplemented groups than the non-supplemented groups at the humerus (12.0% vs. 9.8%, respectively, p < 0.09) and radius-ulna (12.6% vs. 8.6%, respectively, p < 0.01). In conclusion, greater gains in bone mass at loaded sites may be achieved when short bouts of moderate exercise are combined with increased dietary calcium, the former conferring region-specific effects and the latter producing generalized effects. Our randomized, placebo-controlled supplementation study of 160 rural Gambian children aged 8.3-11.9 y showed that an increase in calcium intake of 714 mg/d for 12 mo resulted in a 5% increase in forearm bone mineral acquisition and a 22% decrease in plasma osteocalcin concentration, a bone formation marker, but had no effect on height or bone dimensions.
                We investigated whether these results were sustained after supplement withdrawal.
                All participants were followed up 12 (FU1) and 24 (FU2) mo after supplementation ended. Bone mineral content (BMC), bone mineral density (BMD), and BMC adjusted for bone width, body weight, and height (size-adjusted BMC) were measured at the midshaft and distal radius. Plasma osteocalcin concentration was measured at FU1.
                At follow-up, the calcium group had greater bone mineral status than did the placebo group at the midshaft radius (mean difference +/- SE), FU1: BMC (4.7 +/- 1.6%; P = 0.004), BMD (5.1 +/- 1.1%; P </= 0.0001), size-adjusted BMC (5.0 +/- 1.1%; P </= 0.0001); FU2: BMC (3.8 +/- 1.6%; P = 0.02), BMD (2.7 +/- 1.3%; P = 0.04), size-adjusted BMC (2.5 +/- 1.3%; P = 0.06). Similar differentials were observed at the distal radius but were not significant. No significant differences in plasma osteocalcin concentrations (FU1: -0.5 +/- 6.5%; P = 0.9) were observed between groups.
                Although some of the effects of calcium supplementation were still evident at follow-up, further studies are required to determine whether short-term increases in calcium intake have lasting benefits for Gambian children. The effect of calcium supplementation on bone mineral density (BMD) was evaluated in female twin pairs aged 10-17 years with a mean age of 14 years. Forty-two twin pairs (22 monozygotic, 20 dizygotic; (including one monozygotic pair from a set of triplets) completed at least 6 months of the intervention: 37 pairs to 12 months and 28 pairs to 18 months. BMD was measured by dual-energy X-ray absorptiometry (DXA). In a double-blind manner, one twin in each pair was randomly assigned to receive daily a 1000 mg effervescent calcium tablet (Sandocal 1000), and the other a placebo tablet similar in taste and appearance to the calcium supplement but containing no calcium. Compliance (at least 80% tablets consumed), as measured by tablet count, was 85% in the placebo group and 83% in the calcium group over the 18 months of the study, on average increasing dietary calcium to over 1600 mg/day. There was no within-pair difference in the change in height or weight. When the effect of calcium supplementation on BMD was compared with placebo at approximately 6, 12 and 18 months, it was found that there was a 0.015 +/- 0.007 g/ cm2 greater increase in BMD (1.62 +/- 0.84%) at the spine in those on calcium after 18 months. At the end of the first 6 months there was a significant within-pair difference of 1.53 +/- 0.56% at the spine and 1.27 +/- 0.50% at the hip. However, there were no significant differences in the changes in BMD after the initial effect over the first 6 months. Therefore, we found an increase in BMD at the spine with calcium supplementation in females with a mean age of 14 years. The greatest effect was seen in the first 6 months; thereafter the difference was maintained, but there was no accelerated increase in BMD associated with calcium supplementation. The continuance of the intervention until the attainment of peak bone mass and follow-up after cessation of calcium supplementation will be important in clarifying the optimal timing for increased dietary calcium and the sustained, long-term effects of this intervention. A meta-analysis of adult exercise studies and an infant activity trial show a possible interaction between physical activity and calcium intake on bone. This randomized trial of activity and calcium supplementation was conducted in 239 children aged 3-5 years (178 completed). Children were randomized to participate in either gross motor or fine motor activities for 30 minutes/day, 5 days per week for 12 months. Within each group, children received either calcium (1000 mg/day) or placebo. Total body and regional bone mineral content by DXA and 20% distal tibia measurements by peripheral quantitative computed tomography (pQCT) were obtained at 0 and 12 months. Three-day diet records and 48-h accelerometer readings were obtained at 0, 6, and 12 months. Higher activity levels were observed in gross motor versus fine motor activity groups, and calcium intake was greater in calcium versus placebo (1354 +/- 301 vs. 940 +/- 258 mg/day, p < 0.001). Main effects of activity and calcium group were not significant for total body bone mineral content or leg bone mineral content by DXA. However, the difference in leg bone mineral content gain between gross motor and fine motor was more pronounced in children receiving calcium versus placebo (interaction, p = 0.05). Children in the gross motor group had greater tibia periosteal and endosteal circumferences by pQCT compared with children in the fine motor group at study completion (p < 0.05). There was a significant interaction (both p < or = 0.02) between supplement and activity groups in both cortical thickness and cortical area: among children receiving placebo, thickness and area were smaller with gross motor activity compared with fine motor activity, but among children receiving calcium, thickness and area were larger with gross motor activity. These findings indicate that calcium intake modifies the bone response to activity in young children. Our recent 18-month calcium supplementation trial demonstrated a significant increase in radial bone mineral mass in 7-year-old children with calcium intake approximately 300 mg/day (Am J Clin Nutr 1994; 60: 744-50). The persistence of higher bone mass after cessation of calcium supplementation is unknown. This is a follow-up study to investigate the lasting effect of calcium supplementation on bone acquisition. Subjects were 159 Chinese children aged 8.7 years. Distal one-third radial bone mineral content (BMC) and bone width (BW) were measured by single-photon absorptiometry. After 12 months, the significant difference in mean +/- SD percentage radial BMC disappeared between the study and control groups (7.34 +/- 6.77% vs 8.67 +/- 6.46%, p > 0.05). Dietary calcium intakes were similar between the groups. During the supplementation phase, the study group had 17.9% greater BMC gain than that of controls. In the follow-up phase, however, the study group had 16.1% less BMC gain than that of controls. It appears that an increased acquisition rate during the supplementation phase was almost balanced by a reduced acquisition rate during follow-up phase. Moreover, throughout the entire 30-month period, the overall BMC acquisition rates of the study and control groups were 25% and 23.8%, respectively. Hence, the overall acquisition rate of the study group was only 5% higher than that of controls. Therefore, the effect of calcium supplementation on bone mineral gain appears to reflect a transient reduction in bone turnover rate. Longer-term calcium trials are necessary to confirm whether a sustainable higher calcium intake throughout childhood will enhance peak bone mass. Osteoporosis may be prevented or delayed by maximizing peak bone mass through diet modification and physical activity during adolescence.
                We studied whether increases in calcium intake and physical activity effectively increase the bone mineral status of adolescent girls aged 16-18 y.
                We conducted a 15.5-mo study of calcium supplementation (1000 mg Ca/d as carbonate) in 144 adolescent girls aged 17.3 +/- 0.3 y ( +/- SD). The subjects were randomly allocated to an exercise (three 45-min exercise-to-music classes/wk during term time) or nonexercise group. Dual-energy X-ray absorptiometry of the whole body, spine, forearm, and hip was performed before and after intervention.
                The mean (+/- SD) percentage of subjects compliant with supplement taking was 70 +/- 27% and with exercise class attendance was 36 +/- 25%. Baseline calcium intake was 938 +/- 411 mg/d. Calcium supplementation significantly increased size-adjusted bone mineral content. The effect was stronger in subjects with good compliance (percentage difference +/- SE): whole body, 0.8 +/- 0.3% (P < or = 0.01); lumbar spine, 1.9 +/- 0.5% (P < or = 0.001); ultradistal radius, 1.3 +/- 0.6% (P < or = 0.05); total hip, 2.7 +/- 0.6% (P < or = 0.001); femoral neck, 2.2 +/- 0.7% (P < or = 0.001); trochanter, 4.8 +/- 0.9% (P < or = 0.001). Attendance at > 50% of the exercise sessions was significant at the total hip (1.4 +/- 0.7%; P < or = 0.05) and trochanter (2.6 +/- 1.2%; P < or = 0.05).
                Calcium supplementation and exercise enhanced bone mineral status in adolescent girls. Whether this is a lasting benefit, leading to the optimization of peak bone mass and a reduction in fracture risk, needs to be determined. To evaluate the effect of calcium supplementation on bone acquisition in adolescent white girls.
                A randomized, double-blind, placebo-controlled trial of the effect of 18 months of calcium supplementation on bone density and bone mass.
                Ninety-four girls with a mean age of 11.9 + 0.5 years at study entry.
                University hospital in a small town.
                Calcium supplementation, 500 mg/d calcium as calcium citrate malate; controls received placebo pills.
                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.
                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.
                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. The effect of short-term calcium supplementation on peak bone mass in adolescent girls is not completely defined. In our previous double-blind, placebo-controlled, calcium-supplementation study (1000 mg calcium carbonate/d), we showed that calcium supplementation of postmenarcheal girls with low calcium intakes enhances bone mineral acquisition.
                The objective of this follow-up study, conducted 3.5 y after the end of calcium supplementation, was to investigate the sustained effect of calcium supplementation on bone mineral mass.
                Anthropometric data, nutrient intakes, and bone variables were reassessed in 96 of the 100 adolescent girls whose data had been studied at the end of the supplementation period. Bone mineral content and bone mineral density (BMD) of the total body, lumbar spine, and femoral neck were determined by dual-energy X-ray absorptiometry.
                The calcium-supplemented group tended to have a greater accretion of total-body BMD (TBBMD) than did the control group 3.5 y after the end of supplementation. The finding was statistically significant in the active-treatment cohort (n = 17 in the calcium-supplemented group and 28 in the placebo group), who had a compliance rate of > or =75% during the intervention study. In a multivariate linear-regression analysis, TBBMD accretion from the beginning of the intervention study to the follow-up study in the active-treatment cohort was attributed to calcium supplementation and to the time since inclusion in the initial study.
                Calcium supplementation for 1 y in postmenarcheal girls with low calcium intakes may provide a sustained effect on the basis of TBBMD measurements in participants with compliance rates of > or =75%. There is no agreement on how much calcium young girls need for optimal bone mineralization.
                We evaluated whether the effect of calcium supplementation on whole-body bone mineral accretion depends on habitual calcium intake.
                This was a randomized, double-blind, placebo-controlled, 1-y calcium intervention study of girls aged 12-14 y selected from a larger group according to habitual calcium intake: subgroup A (n = 60) habitually consumed 1000-1307 mg/d (40th-60th percentile), and subgroup B (n = 53) habitually consumed <713 mg/d (<20th percentile). The girls from each subgroup were randomly assigned to receive either 500 mg Ca/d or placebo. Whole-body bone mineral content (BMC), bone area (BA), bone mineral density (BMD), and BMC adjusted for BA, height, and weight (size-adjusted BMC) were measured at baseline and after 1 y.
                There was no significant effect modification of baseline habitual calcium intake on the relation between calcium supplementation and height, weight, BMC, size-adjusted BMC, BA, BMD, or alkaline phosphatase. Calcium supplementation had an effect on BMD (0.8%; P = 0.049) and tended to show signs of an effect on size-adjusted BMC (0.5%; P = 0.08).
                A modest effect of calcium supplementation on BMD was shown. However, the effect was independent of habitual calcium intake. Calcium supplementation during childhood and adolescence is considered an early means of preventing osteoporosis in adults. Prepuberty is an opportune time for detecting the benefits of calcium in girls.
                The objective was to assess whether calcium supplementation increases bone mass gain in prepubertal boys in a skeletal site-specific manner.
                In a 12-month double-blind, placebo-controlled trial with 1-yr follow-up, 235 healthy prepubertal boys aged 7.4 +/- 0.4 yr (mean +/- sd) were randomized to receive two food products providing 850 mg/d calcium (calcium supplement group, n = 116) or an isocaloric placebo (n = 119). Areal bone mineral density (aBMD) was determined by dual-energy x-ray absorptiometry at radius (two sites), hip (two sites), femoral diaphysis (FDia), and L2-L4 vertebrae.
                At 12 months, aBMD gain was greater at the FDia and at the mean of the five appendicular skeletal sites in the calcium supplement group in both intention-to-treat analysis [76 +/- 32 vs. 64 +/- 33 mg/cm(2).yr; difference, 12.0 (95% confidence interval, CI, 3.6-20.3), P = 0.006; and 33 +/- 16 vs. 28 +/- 16 mg/cm(2).yr; difference, 5.1 (95% CI, 0.9-9.2); P = 0.018, respectively] and active treatment analysis [81 +/- 32 vs. 64 +/- 31 mg/cm(2).yr; difference, 17.2 (95% CI, 7.9-26.5); n = 174, P < 0.001; and 35 +/- 16 vs. 28 +/- 14 mg/cm(2).yr; difference, 7.5 (95% CI, 2.9-12.2); P = 0.002]. There was no beneficial effect of calcium on lumbar spine. The calcium effect was still detectable by ANOVA repeated measures analysis at the FDia (P = 0.004) and at the mean of the five appendicular skeletal sites (P = 0.002) 1 yr after the end of intervention (active treatment analysis). There was no change in bone size.
                In prepubertal boys, calcium-enriched foods increased aBMD at several appendicular skeleton sites, but not at the lumbar spine, and this without any bone size change. This effect was maintained 1 yr after treatment discontinuation.
While there is a small effect of calcium supplementation in the upper limb, the increase in BMD which results is unlikely to result in a clinically significant decrease in fracture risk. The results do not support the use of calcium supplementation in healthy children as a public health intervention. These results cannot be extrapolated to children with medical conditions affecting bone metabolism.