Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial

BACKGROUND: Short-term studies established that calcium influences bone accretion during growth. Whether long-term supplementation influences bone accretion in young adults is not known. OBJECTIVE: This study evaluated the long-term effects of calcium supplementation on bone accretion among females from childhood to young adulthood. DESIGN: A 4-y randomized clinical trial recruited 354 females in pubertal stage 2 and optionally was extended for an additional 3 y. The mean dietary calcium intake of the participants over 7 y was approximately 830 mg/d; calcium-supplemented persons received an additional approximately 670 mg/d. Primary outcome variables were distal and proximal radius bone mineral density (BMD), total-body BMD (TBBMD), and metacarpal cortical indexes. RESULTS: Multivariate analyses of the primary outcomes indicated that calcium-supplementation effects vary over time. Follow-up univariate analyses indicated that all primary outcomes were significantly larger in the supplemented group than in the placebo group at the year 4 endpoint. However, at the year 7 endpoint, this effect vanished for TBBMD and distal radius BMD. Longitudinal models for TBBMD and proximal radius BMD, according to the time since menarche, showed a highly significant effect of supplementation during the pubertal growth spurt and a diminishing effect thereafter. Post hoc stratifications by compliance-adjusted total calcium intake and by final stature or metacarpal total cross-sectional area showed that calcium effects depend on compliance and body frame. CONCLUSIONS: Calcium supplementation significantly influenced bone accretion in young females during the pubertal growth spurt. By young adulthood, significant effects remained at metacarpals and at the forearm of tall persons, which indicated that the calcium requirement for growth is associated with skeletal size. These results may be important for both primary prevention of osteoporosis and prevention of bone fragility fractures during growth.     

A randomized controlled trial of phytoestrogen supplementation,growth and bone turnover in adolescent males

OBJECTIVE: To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Single school in northwest Tasmania. PARTICIPANTS: Adolescent boys (treatment n=69, placebo n=59, mean age 16.8 y). INTERVENTIONS: Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up. RESULTS: Despite marked increases in urinary genistein and daidzein in the treatment arm (both P<0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR. CONCLUSIONS: Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.     

Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: a 2-y randomized controlled trial

BACKGROUND: In recent prospective studies, higher homocysteine concentrations were shown to be a risk factor for osteoporotic fractures in older persons. Supplements containing folate and vitamins B-12 and B-6 lower homocysteine concentrations. OBJECTIVE: The objective of the study was to determine in healthy older persons whether lowering homocysteine with B vitamins affects plasma biomarkers of bone turnover. DESIGN: Healthy older persons (n = 276; aged >or=65 y) were randomly assigned to receive either a daily supplement containing folate (1 mg), vitamin B-12 (500 microg), and vitamin B-6 (10 mg) or a placebo for 2 y. Of these participants, we selected 135 with baseline homocysteine concentrations >15.0 micromol/L, and we measured serum bone-specific alkaline phosphatase, a marker of bone formation, and bone-derived collagen fragments, a marker of bone resorption, at baseline and 2 y later. RESULTS: At 2 y, plasma homocysteine concentrations were 5.2 mumol/L (95% CI: 3.9, 6.6 micromol/L; P < 0.001) lower in the vitamin than in the placebo group. No significant differences were found in either serum bone-specific alkaline phosphatase (-0.3 microg/L; 95% CI: -2.8, 2.1 microg/L; P = 0.79) or bone-derived collagen fragments (-0.0 microg/L; 95% CI: -0.1, 0.1 microg/L; P = 0.76) between the vitamin and placebo groups, respectively, with 2 y of supplementation. CONCLUSION: Supplementation with folate and vitamins B-6 and B-12 lowered plasma homocysteine but had no beneficial effect on bone turnover at the end of 2 y, as assessed by biomarkers of bone formation and resorption.     

School-milk intervention trial enhances growth and bone mineral accretion in Chinese girls aged 10-12 years in Beijing

A 2-year milk intervention trial was carried out with 757 girls, aged 10 years, from nine primary schools in Beijing (April 1999 - March 2001). Schools were randomised into three groups: group 1, 238 girls consumed a carton of 330 ml milk fortified with Ca on school days over the study period; group 2, 260 girls received the same quantity of milk additionally fortified with 5 or 8 microg cholecalciferol; group 3, 259 control girls. Anthropometric and bone mineralisation measurements, as well as dietary, health and physical-activity data, were collected at baseline and after 12 and 24 months of the trial. Over the 2-year period the consumption of this milk, with or without added cholecalciferol, led to significant increases in the changes in height (> or =0.6 %), sitting height (> or =0.8 %), body weight (> or 2.9 %), and (size-adjusted) total-body bone mineral content (> or =1.2 %) and bone mineral density (> or =3.2 %). Those subjects receiving additional cholecalciferol compared with those receiving the milk without added 25-hydoxycholecalciferol had significantly greater increases in the change in (size-adjusted) total-body bone mineral content (2.4 v. 1.2 %) and bone mineral density (5.5 v. 3.2 %). The milk fortified with cholecalciferol significantly improved vitamin D status at the end of the trial compared with the milk alone or control groups. It is concluded that an increase in milk consumption, e.g. by means of school milk programmes, would improve bone growth during adolescence, particularly when Ca intake and vitamin D status are low.     

Improving follow-up after an abnormal pap smear: A randomized controlled trial

Less than 60% of women diagnosed with cervical abnormalities on Pap smears return for proper surveillance and timely treatment. Previous tactics used to motivate these women to return have mainly relied on costly intensive recall efforts. Using a framework based on psychological value expectancy theory, a pamphlet was designed to motivate women with abnormal Pap smears to return for a repeat Pap smear. The effect of this pamphlet was tested in a randomized controlled trial. A total of 161 women with abnormal Pap smears were randomized and received either the pamphlet plus a notification letter or the letter only. The compliance rate was 64.2% in the intervention group and 51.3% in the comparison group (P = 0.10; two-tailed). In addition, subgroups of women who do not practice health-related behaviors were identified as groups where more intensive interventions may be needed. These results have implications for future strategies used to recall women with abnormal Pap smears.     

Vitamin D supplementation and bone mass accrual in underprivileged adolescent Indian girls

Vitamin D deficiency is common among children and adolescents in India, in spite of abundant sunshine. We conducted a pilot; double blind randomised controlled trial to investigate the effect of vitamin D supplementation on bone mineral content in underprivileged adolescent girls, in Pune, India. Fifty post-menarcheal girls aged 14 to 15 years were randomised to receive 300,000 IU (7.5 mg) of ergocalciferol or placebo orally, 4 times/year. All participants received 250 mg elemental calcium (calcium carbonate) daily. Outcome measures included change in serum 25-hydroxyvitamin D, size adjusted bone area and bone mineral content at total body and lumbar spine. Post supplementation, the median serum concentration of 25-hydroxyvitamin D was 75.2 (64.2-85.5) nmol/L in the intervention group and 28.1 (16.7-34.0) nmol/L in the placebo group. Increment in bone outcome measures was not different in the two groups. However, there was a positive effect of intervention in the size adjusted total body bone area (p<0.05), total body bone mineral content (p<0.05) and lumbar spine bone mineral content (p<0.05), and positive trend in lumbar spine bone area (p=0.07) in girls who were within 2 years of menarche. We conclude that vitamin D supplementation did not have a beneficial effect on skeletal mineralization in girls who were more than 2 years post menarcheal. However, there was a significant positive effect of the intervention on size adjusted total body and lumbar spine bone mineral content and a positive trend in lumbar spine bone area, in girls who were <= 2 years of menarche.     

An 18-mo randomized trial of a low-glycemic-index diet and weight change in Brazilian women

BACKGROUND: Despite interest in the glycemic index diets as an approach to weight control, few long-term evaluations are available. OBJECTIVE: The objective was to investigate the long-term effect of a low-glycemic-index (LGI) diet compared with that of a high-glycemic-index (HGI) diet; all other dietary components were equal. DESIGN: After a 6-wk run-in, we randomly assigned 203 healthy women [body mass index (in kg/m2): 23-30] aged 25-45 y to an LGI or an HGI diet with a small energy restriction. The primary outcome measure was weight change at 18 mo. Secondary outcomes included hunger and fasting insulin and lipids. RESULTS: Despite requiring a run-in and the use of multiple incentives, only 60% of the subjects completed the study. The difference in glycemic index between the diets was approximately 35-40 units (40 compared with 79) during all 18 mo of follow-up, and the carbohydrate intake from energy remained at approximately 60% in both groups. The LGI group had a slightly greater weight loss in the first 2 mo of follow-up (-0.72 compared with -0.31 kg), but after 12 mo of follow-up both groups began to regain weight. After 18 mo, the weight change was not significantly different (P = 0.93) between groups (LGI: -0.41 kg; HGI: -0.26 kg). A greater reduction was observed in the LGI diet group for triacylglycerol (difference = -16.4 mg/dL; P = 0.11) and VLDL cholesterol (difference = -3.7 mg/dL; P = 0.03). CONCLUSIONS: Long-term weight changes were not significantly different between the HGI and LGI diet groups; therefore, this study does not support a benefit of an LGI diet for weight control. Favorable changes in lipids confirmed previous results.     

A controlled 2-mo dietary fat reduction and soy food supplementation study in postmenopausal women

BACKGROUND: Low intake of dietary fat and high intake of soy foods have been suggested to partly explain the lower breast cancer rates in Asia, perhaps because of lower endogenous estrogens. OBJECTIVE: The objective was to assess the hormonal and nonhormonal effects of diets resembling an Asian diet in terms of total fat and soy food contents. DESIGN: Fifty-seven postmenopausal women participated in a randomized, controlled, dietary intervention study. The subjects consumed a very-low-fat diet (VLFD; 11% of energy as fat), a Step I diet (25% of energy as fat) supplemented with soy food (SFD; 50 mg isoflavones/d), or a control Step I diet (CD; 27% of energy as fat) with no soy food. All diets were prepared at the General Clinical Research Center of the University of Southern California. Serum hormones and other markers were measured at baseline and every 2 wk during the 8 wk of intervention. RESULTS: There were no significant differences in total estradiol and sex hormone binding globulin at the completion of the intervention between women in the SFD and VLFD groups and those in the CD group. Serum insulin decreased significantly in the SFD group, and leptin decreased significantly in the SFD and VLFD groups; however, these changes did not differ significantly from the changes in the CD group. CONCLUSIONS: This study does not provide evidence that ingestion of soy food or a VLFD significantly reduces estrogen concentrations in postmenopausal women. However, short-term changes in diet may have significant and beneficial effects on blood insulin and leptin concentrations.     

Effect of a calcium and exercise intervention on the bone mineral status of 16-18-y-old adolescent girls

BACKGROUND: Osteoporosis may be prevented or delayed by maximizing peak bone mass through diet modification and physical activity during adolescence. OBJECTIVE: We studied whether increases in calcium intake and physical activity effectively increase the bone mineral status of adolescent girls aged 16-18 y. DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.     

Calcium supplements and bone resorption in pregnancy: a randomized crossover trial

BACKGROUND: Pregnancy is a time of increased need for calcium. The role of calcium supplements in altering maternal responses to fetal demand for calcium is not fully understood. This article describes the results of a randomized, crossover trial of calcium supplementation on bone resorption among pregnant women. DESIGN/SETTING PARTICIPANTS: Thirty-one Mexican women at 25-35 weeks gestation participated in the study for 20 days. Each woman received a 1200 mg calcium supplement on 10 consecutive days and a multivitamin without calcium for 10 days. Urine samples were collected daily. Two pooled specimens from each subject (representing urine from multivitamin days and from calcium days) were preserved, and levels of cross-linked, N-telopeptides of type I collagen (NTX), a biomarker of bone resorption, were measured. Dietary calcium intake was assessed using a food-frequency questionnaire. RESULTS: Of the 31 participants, 27 (87.1%) showed reductions in urinary NTX levels while ingesting calcium supplements. When not ingesting calcium, NTX levels for the 31 subjects had a mean of 96.8 nM BCE/mM creatinine; this was significantly higher (p<0.001) than the mean urinary NTX levels of 83.2 nM BCE/mM creatinine during ingestion of the calcium supplements. Neither age nor dietary calcium intake was a significant predictor of treatment effect. CONCLUSION: A bedtime, 1200-mg calcium supplement during the third trimester of pregnancy reduces maternal bone resorption by an average of 13.6 nM BCE/mM creatinine (14%), as reflected by urinary NTX levels. These results suggest that calcium supplements reduce maternal skeletal-bone turnover during the third trimester of pregnancy.     

Effect of calcium supplementation on forearm bone mineral content in postmenopausal women: a prospective, sequential controlled trial

Three hundred ten normal postmenopausal volunteers were invited to enter a controlled trial of the effects of calcium supplementation on forearm mineral content (FMC); 269 entered the study and 210 completed it. Of those who completed the study, 158 were allocated to one of three calcium-supplemented treatment regimes and 52 were allocated to a control group. Twenty-two of the subjects allocated to the treatment group were unable to take supplementary calcium but agreed to remain in the study as additional controls. There were therefore 136 treated subjects, 52 strict controls and 74 controls altogether. During the initial observation period of 9 mo, there was a highly significant loss of bone in all groups (P less than 0.001). During the 9-mo period of treatment, there was a highly significant reduction in the rate of bone loss in the treated subjects (P less than 0.001), a just significant reduction in the strict controls (P less than 0.05) and a nonsignificant reduction in the rate of loss in all controls. The difference between the treated and strict controls in the second period was not significant but the difference between the treated and all controls in the second period was significant (P less than 0.025). When the analysis was applied only to women within 10 yr of menopause, the difference between the treated and strict control groups in period 2 was significant (P less than 0.025) and the difference between the treated and all controls was highly significant (P less than 0.001).     

The skeletal benefits of calcium- and vitamin D3-fortified milk are sustained in older men after withdrawal of supplementation: an 18-mo follow-up study

BACKGROUND: In a previous 2-y randomized controlled trial, we showed that calcium- and vitamin D3-fortified milk stopped or slowed bone loss at several clinically relevant skeletal sites in older men. OBJECTIVE: The present study aimed to determine whether the skeletal benefits of the fortified milk were sustained after withdrawal of the supplementation. DESIGN: One hundred nine men >50 y old who had completed a 2-y fortified milk trial were followed for an additional 18 mo, during which no fortified milk was provided. Bone mineral density (BMD) of the total hip, femoral neck, lumbar spine, and forearm was measured by using dual-energy X-ray absorptiometry. RESULTS: Comparison of the mean changes from baseline between the groups (adjusted for baseline age, BMD, total calcium intake, and change in weight) showed that the net beneficial effects of fortified milk on femoral neck and ultradistal radius BMD at the end of the intervention (1.8% and 1.5%, respectively; P < 0.01 for both) were sustained at 18-mo follow-up (P < 0.05 for both). The nonsignificant between-group differences at the total hip (0.8%; P = 0.17) also persisted at follow-up (0.7%; P = 0.10), but there were no lasting benefits at the lumbar spine. The average total dietary calcium intake in the milk supplementation group at follow-up approximated recommended amounts for Australian men >50 y old (1000 mg/d) but did not differ significantly from that in the control subjects (1021 versus 890 mg/d). CONCLUSION: Supplementation with calcium- and vitamin D3-fortified milk for 2 y may provide some sustained benefits for BMD in older men after withdrawal of supplementation.     

Sustained effect of short-term calcium supplementation on bone mass in adolescent girls with low calcium intake

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: 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%.     

Effect of protein and methionine intakes on plasma homocysteine concentrations: a 6-mo randomized controlled trial in overweight subjects

BACKGROUND: A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease. Homocysteine concentrations are thought to be raised by high protein and methionine intakes. OBJECTIVE: Our goal was to investigate the effects of high and low protein and methionine intakes on homocysteine in overweight subjects. DESIGN: Sixty-five overweight subjects were randomly assigned to a 6-mo intervention with a low-protein, low-methionine diet (LP: 12% of total energy, 1.4 g methionine/d; n = 25); a high-protein, high-methionine diet (HP: 22% of total energy, 2.7 g methionine/d; n = 25), both of which had similar fat contents (30% of total energy); or a control diet with an intermediate protein content (n = 15). All food was self-selected at a shop at the department. Protein intake was increased in the HP group mainly through lean meat and low-fat dairy products. Dietary compliance was evaluated by urinary nitrogen excretion. RESULTS: Homocysteine concentrations did not change significantly in the LP or control groups but were 25% lower in the HP group (NS). Homocysteine concentrations after the 3-mo intervention were inversely associated with vitamin B-12 intake and with weight change (by multivariate analysis performed for all subjects), but not with methionine or protein intake. Sixty-nine percent of the variation could be explained by baseline homocysteine (P < 0.001), 2% by vitamin B-12 (P = 0.02), and another 2% by weight change (P = 0.06). The plasma homocysteine concentration after 6 mo was associated only with baseline homocysteine (P < 0.001). CONCLUSION: A high-protein, high-methionine diet does not raise homocysteine concentrations compared with a low-protein, low-methionine diet in overweight subjects.     

Effects of an exercise program and a calcium supplementation on bone in children: a randomized control trial

We investigated the effects of calcium supplementation and physical practice on the bone ultrasound properties and trabecular microarchitecture in children. 160 children aged 8-11 were randomly allocated to active or nonactive groups and to receive either a calcium-phosphate or a placebo powder for 6 months. Skeletal status was assessed using an ultrasound technique, which measures the speed of sound (Ad-SoS, m/s) at the phalanx. Bone microarchitecture was characterized by fractal analysis measured on calcaneus radiographs and the result expressed as the Hmean parameter, that has been shown to a good reliability of the bone texture quality. After 6 months, the calcium group had significantly gained Ad-SoS compared to the placebo group (P = 0.01) and Hmean increase was greater in the active than the nonactive group (P < 0.05). Exercise and calcium supplementation had a differential effect on the bone tissue, calcium being rather linked to a systemic effect whereas exercise has acted better onto the skeletal stressed site.     

Antioxidant supplementation with or without B-group vitamins after acute ischemic stroke: a randomized controlled trial

BACKGROUND: Evidence shows that there is a rapid increase in the production of markers of oxidative damage immediately after acute ischemic stroke and that endogenous antioxidant defenses are rapidly depleted, thus permitting further tissue damage. Several studies point to an antioxidant effect of B-group vitamins and a pro-oxidant effect of elevated total plasma homocysteine (tHcy). METHODS: To test whether supplementary antioxidants with or without B-group vitamins during this critical period enhance antioxidant capacity or mitigate oxidative damage, ninety-six acute ischemic stroke patients within 12 hours of symptom onset were randomly assigned to receive either daily oral 800 IU (727 mg) vitamin E and 500 mg vitamin C (n = 24), or B-group vitamins (5 mg folic acid, 5 mg vitamin B(2), 50 mg vitamin B(6), and 0.4 mg of vitamin B(12); n = 24), both vitamins together (n = 24), or no supplementation (n = 24) for 14 days. Treatment groups and controls were matched for stroke subtype and age. Blood was obtained before treatment, at day 7, and day 14 for measurements of plasma or blood vitamin status, plasma total antioxidant capacity (TAOC), malondialdehyde (MDA), tHcy and C-reactive protein (CRP). RESULTS: Supplementation with antioxidant vitamins and B-group vitamins separately or together significantly increased the plasma concentration of vitamin C, E, pyridoxal phosphate (B(6) status), red blood cell folate, and improved a measure of B(2) status (red cell glutathione reductase activation coefficient [EGRAC]), compared with the control group. Plasma TAOC increased significantly in the antioxidant treatment groups compared with the nonsignificant decline seen in the control group. tHcy concentrations decreased in subjects who received B-group vitamins and the control group compared with the rise seen in those who received antioxidants alone. There was a significant reduction in plasma MDA concentration in the 3 treatment groups, in contrast to the increase seen in the control group; however, the changes were most evident in antioxidant groups. CRP concentrations (a marker of tissue inflammation) were significantly lower in the 3 treatment groups compared with the control group. There were no additive or synergistic effects of antioxidants and B-group vitamins together on any outcome measure. CONCLUSIONS: Antioxidants supplementation with or without B-group vitamins enhances antioxidant capacity, mitigates oxidative damage, and may have an anti-inflammatory effect immediately postinfarct in stroke disease.