Randomized trial of physical activity and calcium supplementation on bone mineral content in 3- to 5-year-old children. Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease. Randomised double blind placebo controlled trial investigating the effect of calcium and vitamin D supplementation on bone mineral density and bone metabolism in adult patients with cystic fibrosis. 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. A co-twin study of the effect of calcium supplementation on bone density during adolescence. Cumulative effects of calcium supplementation and physical activity on bone accretion in premenarchal children: a double-blind randomised placebo-controlled trial. Effect of a calcium and exercise intervention on the bone mineral status of 16-18-y-old adolescent girls. A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. Iatrogenic osteomalacia in epileptic children. A controlled therapeutic trial. Sustained effect of short-term calcium supplementation on bone mass in adolescent girls with low calcium intake. Bone mineral acquisition in low calcium intake children following the withdrawal of calcium supplement. Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1 alpha-hydroxyvitamin D3 and calcium supplementation. Bone mineral contents and plasma osteocalcin concentrations of Gambian children 12 and 24 mo after the withdrawal of a calcium supplement.
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. A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and may have osteoporosis. We previously showed deficiency of vitamins D and K1 causes reduced bone mineral density (BMD) in female AD patients. The present study was undertaken to address the possibility that treatment with vitamin K2 (menatetrenone; MK-4) may maintain BMD and reduce the incidence of nonvertebral fractures in elderly female patients with AD. In a random and prospective study of AD patients, 100 patients received 45 mg menatetrenone, 1000 IU ergocalciferol and 600 mg calcium daily for 2 years, and the remaining 100 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K1 deficiencies. They also had high serum levels of parathyroid hormone (PTH) and Glu osteocalcin (OC) and low serum ionized calcium, indicating that vitamin D deficiency stimulates compensatory PTH secretion. During the 2-year study period, BMD in the second metacarpals increased by 2.3% in the treated group and decreased by 5.2% in the untreated group (P < 0.0001). Serum levels of vitamin K2 and 25-hydroxyvitamin D increased by 284.9% and 147.9%, respectively, in the treated group. Correspondingly, a significant decrease in Glu OC and PTH were observed, in association with an increased calcium levels, in the treated group. Twenty-two patients in the untreated group sustained nonvertebral fractures (15 with hip fractures, two fractures each at the distal forearm and the proximal femur, each one fracture at the proximal humerus, ribs, and pelvis), and three fractures (2 with hip fractures, one fracture at the proximal femur) occurred among the treated patients (P = 0.0003; odds ratio = 7.5). Treatment with MK-4 and vitamin D2 with calcium supplements increases the BMD in elderly female patients with AD and leads to the prevention of nonvertebral fractures. Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis and might be related to calcium and vitamin D malabsorption from the gastrointestinal tract. The aim of this study was to investigate the effect of calcium and vitamin D supplementation on BMD and bone metabolism in these subjects.
                Patients were invited to participate if they had a BMD Z score of -1 or less in the lumbar spine, proximal femur or distal forearm. Patients were randomised to receive calcium 1 g+vitamin D 800 IU or placebo daily, in addition to their regular vitamin D supplements (900 IU/day). BMD and bone biochemical markers were measured before and after 1 year of treatment.
                After 12 months, the treatment group (n=15) showed a reduced rate of bone loss compared with the control group (n=15) in the lumbar spine (mean difference 1.9% [CI -0.9% to 4.6%]), total hip (mean difference 0.7% [CI -2.2% to 3.5%]) and distal forearm (mean difference 1.7% [CI -2.2% to 5.5%]), but these changes did not reach statistical significance. There was also a trend towards a reduction in bone turnover in the treatment group.
                Calcium and vitamin D supplementation reduced the rate of bone turnover and bone loss in adult patients with cystic fibrosis, but these changes did not reach statistical significance. These data suggest that a longer term trial of this simple intervention would be justified. 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. 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. 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. 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. The effect of vitamin D supplementation on bone mineral augmentation in 212 adolescent girls with adequate calcium intake was studied in a randomized placebo-controlled setting. Bone mineral augmentation determined by DXA increased with supplementation both in the femur and the lumbar vertebrae in a dose-responsive manner. Supplementation decreased the urinary excretion of resorption markers, but had no impact on formation markers.
                Adequate vitamin D intake protects the elderly against osteoporosis, but there exists no indisputable evidence that vitamin D supplementation would benefit bone mineral augmentation. The aim of this 1-year study was to determine in a randomized double-blinded trial the effect of 5 and 10 microg vitamin D3 supplementation on bone mineral augmentation in adolescent girls with adequate dietary calcium intake.
                Altogether, 228 girls (mean age, 11.4 +/- 0.4 years) participated. Their BMC was measured by DXA from the femur and lumbar spine. Serum 25-hydroxyvitamin D [S-25(OH)D], intact PTH (S-iPTH), osteocalcin (S-OC), and urinary pyridinoline (U-Pyr) and deoxypyridinoline (U-Dpyr) were measured. Statistical analysis was performed both with the intention-to-treat (IT) and compliance-based (CB) method.
                In the CB analysis, vitamin D supplementation increased femoral BMC augmentation by 14.3% with 5 microg and by 17.2% with 10 microg compared with the placebo group (ANCOVA, p = 0.012). A dose-response effect was observed in the vertebrae (ANCOVA, p = 0.039), although only with the highest dose. The mean concentration of S-25(OH)D increased (p < 0.001) in the 5-microg group by 5.7 +/- 15.7 nM and in the 10-microg group by 12.4 +/- 13.7 nM, whereas it decreased by 6.7 +/- 11.3 nM in the placebo group. Supplementation had no effect on S-iPTH or S-OC, but it decreased U-DPyr (p = 0.042).
                Bone mineral augmentation in the femur was 14.3% and 17.2% higher in the groups receiving 5 and 10 microg of vitamin D, respectively, compared with the placebo group, but only 10 mug increased lumbar spine BMC augmentation significantly. Vitamin D supplementation decreased the concentration of bone resorption markers, but had no impact on bone formation markers, thus explaining increased bone mineral augmentation. However, the positive effects were noted with the CB method but not with IT. Bone mineral content (BMC) ub tge forearms (related to total body calcium) was measured for a controlled therapeutic trial in 25 epileptic children on long-term treatment with phenytoin and in 22 normal children before and during treatment with vitamin D or placebo. In the epileptic children, hypocalcaemia and elevated serum alkaline phosphatase was found in 20% and 16%, respectively. The group of epileptic children treated with vitamin D2 (2000 IU daily) for 3 months showed a significant increase in bone mineral content, 5% on average. The epileptic children treated with placebo showed a significant decrease, 2% on average, while the normal children treated with vitamin D or placebo showed no change in bone mineral content. The results indicate a possible benefit of prophylactic vitamin D treatment in epileptic children. 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%. 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. It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients, which might increase their risk of hip fracture. We evaluated the efficacy of 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke.
                In a randomized study, 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 microgram 1 alpha (OH)D3 daily (treatment group, n = 30) or an inactive placebo (placebo group, n = 34) for 6 months and were observed for this duration. Both groups received 300 mg of elemental calcium daily. The bone mineral density (BMD) and metacarpal index (MCI) in the second metacarpals were determined by computed x-ray densitometry. The incidence of hip fractures in these patients was recorded.
                BMD on the hemiplegic side decreased by 2.4% in the treatment group and 8.9% in the placebo group (P = .0021), while BMD on the intact side increased by 3.5% and decreased by 6.3% in the treated and placebo groups, respectively (P = .0177). In the treatment group, the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before randomization. This difference increased in the placebo group. We observed a similar improvement in MCI in the treatment group but not in the placebo group. Four patients in the placebo group suffered a hip fracture compared with none in the treatment group (P = .0362).
                Treatment with 1 alpha (OH)D3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-standing stroke. Treatment also may improve these indices on the intact side. 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.
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.