Calcium intake and bone mass

The deficiency of calcium intake during childhood blocks the attainment of normal peak bone mass. On the other hand, oral calcium supplement is effective for suppressing bone loss in postmenopausal women. This effect is prominent especially in older women as well as women with lower calcium intake, and in cortical bone, compared with cancellous bone. Thus, the deficiency of calcium intake is considered to be one of major risk factors for osteoporosis, but no clear evidence have been available in Japan.     

Effect of calcium intake vs. other life-style factors on bone mass.

Several life-style factors are known to or have been suggested to interact with calcium metabolism and bone turnover. Immobilization or a sedentary life-style may result in substantial bone loss, and physical exercise may increase bone mass, to different extents in different parts of the skeleton. Excessive training and/or slimming may lead to amenorrhoea, which is in turn complicated by rapid bone loss. While calcium supplementation probably cannot override the negative calcium balance induced by immobilization or amenorrhoea, the calcium requirement may be enhanced during recovery from these states. A high body mass index may to some extent protect against bone loss, particularly in post-menopausal women. Tobacco smoking and high alcohol consumption are probably detrimental to bone mass. Insufficient exposure to daylight and/or insufficient vitamin D intake occur mainly in infants and elderly people, and may impair calcium balance and cause rickets, osteomalacia or osteoporosis. Whether high intake of caffeine, protein, phosphate or fibre is detrimental to the bone mass has not yet been clarified. In many populations smoking and consumption of alcohol or caffeine are negatively correlated with calcium intake, and this exemplifies a source of confounding factors. Increased attention would be paid to important life-style factors during investigations of calcium requirements in different sex and age categories.     

Changes in calcium kinetics in adolescent girls induced by high calcium intake

To identify the mechanism/s whereby calcium retention is increased by calcium intake in adolescent girls, kinetic studies were performed using stable calcium isotope tracers. Girls (n = 10; 12 +/- 1 yr old, mean +/- SD) were studied while on a controlled diet containing a low (21.2 mmol/day) and a high (47.4 mmol/day) calcium intake, in randomized order, using a cross-over design. Studies were separated by 1 month. Calcium tracers were administered after 1 week on the study diet, orally and iv; and serum, urine, and feces were collected for the following 14 days. Tracers were measured using fast atom bombardment mass spectrometry, and kinetic data were analyzed by compartmental modeling. Biochemical markers of bone turnover were measured in serum and urine samples. On high (compared with low) calcium intake, fractional absorption did not differ, absorbed calcium increased (19.6 +/- 7.5 vs. 8.0 +/- 2.5 mmol/day, mean +/- SD, P: < 0.001), calcium excreted in urine increased (2.8 +/- 1.7 vs. 2.1 +/- 1.1 mmol/day, P: < 0.01), calcium retained in bone increased (14.5 +/- 8.9 vs. 3.2 +/- 3.6 mmol/day, P: < 0.001), bone formation did not change, and bone resorption decreased by 32%. These changes, measured by kinetics, were corroborated by changes in markers of bone turnover. We conclude that increased bone retention of calcium, with high calcium intake in adolescent girls, is attributable to an increase in absorption and a decrease in bone resorption.     

Controlled trial of low calcium versus high calcium intake in mild hypertension

A controlled trial of the effect of low versus high calcium intake on blood pressure was performed in 15 patients with mild essential hypertension (supine blood pressure after a 1-month run-in period: 145.7 +/- 2.6/97.8 +/- 0.9 mmHg, mean +/- s.e.m.). After a 1-week baseline period on a standard calcium intake (900 mg/day, obtained by giving a 500-mg calcium tablet daily, in addition to a 400-mg calcium diet), the patients were randomly entered into a double-blind crossover study of 4-week low calcium intake (400 mg calcium diet plus two placebo tablets/day) and 4-week high calcium intake (1400 mg/day: 400-mg calcium diet plus two 500-mg calcium tablets/day). Compliance with the diets appeared to be satisfactory, based on the results of food record analysis. No significant blood pressure change was observed at the end of the low-compared to the high-calcium regimen. Serum ionized calcium was slightly, but not significantly lower, while 24-h urinary calcium excretion was significantly reduced during the low-calcium diet. No difference was found in urinary sodium and potassium excretion between the two study periods. We conclude that moderate modifications of oral calcium intake are not associated with changes in blood pressure within the time span of this study.     

Bone metabolism markers predict increase in bone mass, height and sitting height during puberty depending on the VDR Fok1 genotype

Objectives Longitudinal growth and bone mass accumulation are two important phenomena during puberty, resulting in attainment of peak bone mass (PBM) and final height. They are thought to be under strong genetic control, with the vitamin D receptor (VDR) gene being among the candidate genes. Bone metabolism markers are reported to be good predictors of longitudinal growth and bone mass increase. The purpose of this longitudinal study was to evaluate whether bone metabolism markers predict bone mass and height increase differently according to Fok1 VDR genotype throughout puberty in healthy adolescents. Patients and measurements At the start of the study 130 girls were aged 10·8 (range 8·5–12·8) years and 125 boys were aged 11·8 (range 9·4–14·6) years at the first visit. Markers of bone formation and bone resorption were measured at the first visit, as well as height and sitting height (SH), and bone mineral content (BMC) of the lumbar spine, femur, arm and total body. All measurements were repeated after 2 years. Results A higher BMC of the femur, distal arm and total body was found in ff boys at the first visit, which was not related to higher levels of bone metabolism markers in this group. In girls, no differences between genotypes were seen in BMC (increase). However, concentrations of markers of bone formation [alkaline phosphatase (AP), bone‐specific alkaline phosphatase (BAP), procollagen aminoterminal propeptide (PINP)] and bone resorption [type I carboxyterminal telopeptide (ICTP)] were higher in ff girls. Regression coefficients between bone metabolism markers and bone mass increase differed according to genotype and sex. A similar pattern was found for height and SH (increase), the latter as a representative of growth of the axial skeleton, mainly consisting of cancellous bone. Conclusions Our data suggest that the predicting capacities of bone metabolism markers on bone mass (increase), height and SH (increase) are genotype dependent. Their use as predictors of final height or PBM therefore remains questionable without knowing the genotype.     

Quantitative ultrasound of bone and calcium intake in suburban males in Sri Lanka

Background: While only 30% of all hip fractures occurred in Asia in 1990, more than 50% will occur by the year 2050. We investigated the relationship between the Stiffness Index (SI), assessed with quantitative ultrasound, and calcium intake in a cross‐sectional survey of suburban males of different ages. Methods: From 496 people who were invited, 274 participated (55%). A single operator performed quantitative ultrasound measurements at the right calcaneus using Lunar Achilles. We derived the Sri Lankan T‐score values for SI. Calcium intake was measured using semiquantitative food frequency questionnaire to measure the previous 7 days intake. Results: There was gradual decrease in mean SI from the age of 30 years. Eighty percent of the men between 21–40 years had normal T‐scores. This percentage value fell to high 60s in men between 41–70 years. After 71 years, 35% had normal T‐scores and 30% had T‐scores less than –2.5. The mean calcium intake was 197 mg/day (95% CI 187–287 mg). Conclusions: This is the first population‐based study done in Sri Lanka regarding calcium intake and SI in males. Although few men had low T‐scores according to SI after 40 years, bone health of elderly (after 71 years) is at risk levels. The overall prevalence of low SI was negligible (4%) even with low calcium intake. Age is the only factor that influenced SI.     

Interaction between calcium intake and menarcheal age on bone mass gain: an eight-year follow-up study from prepuberty to postmenarche

Both late menarcheal age and low calcium intake (Ca intake) during growth are risk factors for osteoporosis, probably by impairing peak bone mass. We investigated whether lasting gain in areal bone mineral density (aBMD) in response to increased Ca intake varies according to menarcheal age and, conversely, whether Ca intake could influence menarcheal age. In an initial study, 144 prepubertal girls were randomized in a double-blind controlled trial to receive either a Ca supplement (Ca-suppl.) of 850 mg/d or placebo from age 7.9-8.9 yr. Mean aBMD gain determined by dual energy x-ray absorptiometry at six sites (radius metaphysis, radius diaphysis, femoral neck, trochanter, femoral diaphysis, and L2-L4) was significantly (P = 0.004) greater in the Ca-suppl. than in the placebo group (27 vs. 21 mg/cm(2)). In 122 girls followed up, menarcheal age was recorded, and aBMD was determined at 16.4 yr of age. Menarcheal age was lower in the Ca-suppl. than in the placebo group (P = 0.048). Menarcheal age and Ca intake were negatively correlated (r = -0.35; P < 0.001), as were aBMD gains from age 7.9-16.4 yr and menarcheal age at all skeletal sites (range: r = -0.41 to r = -0.22; P < 0.001 to P = 0.016). The positive effect of Ca-suppl. on the mean aBMD gain from baseline remained significantly greater in girls below, but not in those above, the median of menarcheal age (13.0 yr). Early menarcheal age (12.1 +/- 0.5 yr): placebo, 286 +/- 36 mg/cm(2); Ca-suppl., 317 +/- 46 (P = 0.009); late menarcheal age (13.9 +/- 0.5 yr): placebo, 284 +/- 58; Ca-suppl., 276 +/- 50 (P > 0.05). The level of Ca intake during prepuberty may influence the timing of menarche, which, in turn, could influence long-term bone mass gain in response to Ca supplementation. Thus, both determinants of early menarcheal age and high Ca intake may positively interact on bone mineral mass accrual.     

Hormonal determinants of bone turnover before and after attainment of peak bone mass

Introduction Bone turnover decreases from adolescence into adulthood, but does not reach a nadir until the fourth decade. Biochemical markers of bone turnover reflect different processes before and after peak bone mass, so hormonal influences on bone turnover may differ before and after peak bone mass. Objectives To describe the changes in bone turnover and hormones relevant to bone metabolism from adolescence into adulthood, and to identify which hormones correlate with bone turnover before and after peak bone mass. Design/participants Two measurements of bone turnover markers and hormones were obtained 5–9 years apart in 116 healthy males and females recruited from secondary schools and general practices. Correlations were examined cross‐sectionally and longitudinally. Results Dehydroepiandrosterone sulphate (DHEAS) correlated negatively with bone turnover cross‐sectionally and longitudinally (r?0·59 to ?0·69) in males and females under the age of 25 years. IGF‐1 correlated positively with aminoterminal propeptide of type I procollagen (PINP) cross‐sectionally and longitudinally (r 0·35) in women over the age of 25 years. After correction for change in BMI, there were significant longitudinal correlations between DHEAS and bone turnover in women under 25 years (r?0·62, ?0·66) and IGF‐1 and PINP in women over 25 years (r 0·56). Conclusions We have described changes in bone turnover and hormones from adolescence into adulthood. Dehydroepiandrosterone sulphate correlates with bone turnover before peak bone mass which may represent a direct effect on bone metabolism or the role of dehydroepiandrosterone sulphate as a substrate for conversion to other sex steroids. IGF‐1 is correlated with aminoterminal propeptide of type I procollagen in women after peak bone mass, which may reflect an influence on cortical modelling.     

Prevention of bone demineralization by calcium supplementation in precocious puberty during gonadotropin-releasing hormone agonist treatment.

We have previously demonstrated a negative impact on peak bone mass in girls with precocious puberty treated with GnRH agonist (GnRHa). Several studies have shown that a high calcium intake positively influences bone mass in prepubertal girls and leads to a higher peak bone mass. The aim of this study was to evaluate the effect of calcium supplementation in girls with precocious puberty during GnRHa treatment. Forty girls affected by true central precocious puberty and treated with the GnRHa triptorelin were studied for 2 yr. After diagnosis, the patients were randomly assigned to three groups: group A, treated only with GnRHa; group B, treated for 12 months solely with GnRHa and then supplemented with calcium gluconolactate/carbonate (1 g calcium/day in two doses) for 12 months; and group C, treated from the beginning with combined GnRHa and calcium. Bone mineral density (BMD) at the lumbar spine was measured by dual energy x-ray absorptiometry at the beginning of the study and after 12 and 24 months and was expressed as the calculated true volumetric density (BMDv) in milligrams per cm3. Group A showed a decrease in absolute BMDv levels, in SD score for chronological age (CA), and even more in SD score for bone age (BA). Group B showed the same behavior during the first year, but this trend was reversed in the second year, when calcium supplementation was added to GnRHa treatment. Group C showed an increase in absolute BMDv levels and in SD score for CA and BA. BMDv variations (expressed as absolute values, SD score for CA, and SD score for BA) became statistically significant at 24 months between groups C and A (P = 0.036, P = 0.032, and P = 0.025, respectively). The behavior of the lumbar spine BMDv in the three groups is consistent with a positive effect of calcium supplementation during GnRHa treatment. In calcium-supplemented patients, the normal process of bone mass accretion at puberty is preserved despite GnRHa treatment. Therefore, the reduction in BMD during GnRHa treatment in girls with precocious puberty is at least completely reversible and preventable if calcium supplementation is associated from the beginning.     

Bone mass at final height in precocious puberty after gonadotropin-releasing hormone agonist with and without calcium supplementation

The aim of our longitudinal study was to evaluate bone mass in girls affected by central precocious puberty (CPP) that have reached final height, treated with GnRH agonist triptorelin (GnRHa), with or without calcium supplementation. We studied 48 Caucasian females affected by CPP (age at diagnosis, 7.19 +/- 0.96 yr), randomly assigned to two groups: group A (n = 21) treated with GnRHa and group B (n = 27) treated with GnRHa plus calcium gluconolactate and carbonate (1 g calcium/day in two doses) for at least 2 yr. Auxological parameters (standing height, weight, body mass index) and bone mineral density (BMD) at the lumbar spine [L2-L4, anteroposterior (AP)-BMD; lateral BMD; volumetric (v)BMD)] by dual-energy x-ray absorptiometry were evaluated at the beginning [chronological age (CA), 7.29 +/- 0.91 yr; bone age (BA), 8.80 +/- 1.24 yr] and end of treatment (CA, 11.27 +/- 0.97 yr; BA, 12.35 +/- 0.43 yr) and at final height (CA, 16.17 +/- 1.9 yr; BA, 16.93 +/- 0.98 yr, in each case >15 yr). Total bone mineral content, total BMD, and fat percentage were evaluated at the end of the study period using dual-energy x-ray absorptiometry. Final height was significantly higher than predicted height at diagnosis (159.9 +/- 6.3 cm vs. 152.9 +/- 9.6 cm; P < 0.05). Body mass index and fat percentage were not statistically different from control values. Densitometric values at final evaluation in groups A and B together were lower than in controls, but the differences were not statistically significant. The vBMD was significantly higher in group B than in group A at the end of treatment period (0.213 +/- 0.022 g/cm(3) vs. 0.192 +/- 0.021 g/cm(3); P < 0.01) and at final evaluation (0.246 +/- 0.023 g/cm(3) vs. 0.227 +/- 0.024 g/cm(3); P < 0.05). The percentage change (Delta%) between the start and end of treatment period in AP-BMD and vBMD was significantly higher in group B than in group A (Delta% AP-BMD: 20.36% +/- 1.10% vs. 16.16% +/- 1.90%, P < 0.01; Delta% vBMD: 19.08% +/- 3.52% vs. 9.26% +/- 5.15%; P < 0.01) and also between the start of treatment and final evaluation (Delta% AP-BMD: 61.23% +/- 1.61% vs. 56.97% +/- 1.45%, P < 0.01; Delta% vBMD: 36.69% +/- 5.01% vs. 28.01% +/- 5.76%, P < 0.01). In all our females with CPP treated with GnRHa, bone densitometric parameters were in the normal range for age and sex. However, bone mass achievement seemed to be better preserved in the group of patients supplemented with calcium.     

Long-term potassium citrate therapy and bone mineral density in idiopathic calcium stone formers

Several authors have described an association between idiopathic calcium (Ca) stone disease and bone mass reduction. Hypocitraturia is a frequent feature of urolithiasis, and alkaline citrate has been recommended as one of the choice treatments in this disease. Some evidence exists as to the positive effect of potassium (K) citrate therapy on bone mass. The aim of this work was the longitudinal evaluation of bone mineral density (BMD) changes in a group of Ca oxalate stone formers treated with K citrate for two years. Enrolled patients were 120; 109 subjects completed the study (51 males and 58 females). A metabolic study and distal radius BMD measurements were conducted both at baseline (BAS) and at the end of the study (END). BMD (0.451 +/- 0.081 vs 0.490 +/- 0.080 g/cm2), T-score (-1.43 +/- 1.02 vs -0.90 +/- 1.04), net gastrointestinal alkali absorption (40.37 +/- 50.57 vs 61.26 +/- 42.26 mEq/day), urinary citrate (2.53 +/- 1.15 vs 3.10 +/- 1.44 mmol/day) and K (58.93 +/- 22.28 vs 65.45 +/- 23.97 mmol/day) excretion significantly increased from BAS to END. Urinary Ca excretion remained unchanged from BAS to END (5.16 +/- 2.74 vs 5.57 +/- 2.85 mmol/ day). Our results indicate that long-term treatment with K citrate increases forearm BMD in idiopathic Ca stone formers. It seems probable that the alkali load provided by this drug reduces bone resorption by a buffering of the endogenous acid production. K citrate appears to be a further therapeutic opportunity for the management of osteoporosis in Ca stone formers.     

Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence

Maximizing peak bone mass is advocated as a way to prevent osteoporosis. As a prerequisite to the elaboration of any preventive program aimed at maximizing peak bone mass, it is important to determine how the rate of skeletal growth at clinically relevant sites, such as lumbar spine and femoral neck, proceeds in relation to age and pubertal stages in both sexes. Bone mass was assessed in 207 healthy caucasian boys and girls, aged 9-18 yr. Bone mineral density (BMD; grams per cm2) and content (BMC; grams) were determined in lumbar spine (L2-L4), femoral neck (FN), and midfemoral shaft (FS), using dual energy x-ray absorptiometry. Bone variables were correlated with both chronological age and pubertal stage, and compared with young adult (20-35 yr) reference values. The main results are: 1) in males, compared to females, there was a marked age-related delay in L2-L4 BMD or BMC increase, but no delay was observed in relation to pubertal stages; 2) at the end of the rapid growth spurt, trends for higher mean values in males were observed for L2-L4 BMC, FN BMD, and particularly FS BMD, but no sex difference was observed for L2-L4 BMD; 3) in females, but not in males, a dramatic reduction in bone mass growth was observed after 15 yr of age, particularly for L2-L4 BMD/BMC and FN BMD. This sharp reduction occurred between the second and fourth years after menarche. In the 14- to 15-yr-old female group, BMD in L2-L4, FN, and FS corresponded to 99.2%, 105.1%, and 94.1%, respectively, and BMC in L2-L4 to 97.6% of the mean values recorded in 20- to 35-yr-old women. In conclusion, this cross-sectional study indicates that during pubertal development, major differences are observed in bone mass growth according to sex and skeletal site. Whereas in males bone mass at different skeletal sites continues to increase substantially between 15-18 yr, skeletal mass growth appears to dramatically slow down at the levels of both lumbar spine and FN at 15-16 yr of age in female adolescents. This suggests that the generally accepted notion that in both males and females bone mass continues to substantially accumulate at all skeletal sites until the fourth decade may not be a constant in human physiology.     

Isoflavone consumption does not increase the bone mass in osteopenic obese female zucker rats

Some controversy exists in the literature concerning the effects of leptin on bone metabolism. Thus we have compared femoral bone density and biochemical markers of bone metabolism in male and female fatty (leptin-resistant) Zucker rats and their lean homozygous controls at 3 and 6 months of age. At 3 months, no differences concerning total, diaphyseal (cortical bone), and distal metaphyseal (trabecular bone) femoral bone densities, plasma osteocalcin concentrations, and urinary deoxypyridinoline excretion were observed between fatty and lean rats. On the opposite, at 6 months of age, in both males and females, total, diaphyseal, and distal metaphyseal femoral bone densities and plasma osteocalcin concentrations were lower in Zucker than in lean rats. Soybean isoflavone consumption (40 microg/g body weight/day for 90 days, a dose which prevents osteopenia following ovariectomy both in lean Zucker homozygous controls and in Wistar rats) by obese female Zucker rats had no significant effect upon their bone mass.     

Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass

Little is known about the effects on the skeleton of laparoscopic Roux-en-Y gastric bypass (LRGB) surgery for morbid obesity and subsequent weight loss. We compared 25 patients who had undergone LRGB 11 +/- 3 months previously with 30 obese controls matched for age, gender, and menopausal status. Compared with obese controls, patients post LRGB had significantly lower weight (92 +/- 16 vs. 133 +/- 20 kg; P < 0.001) and body mass index (31 +/- 5 vs. 48 +/- 7 kg/m(2); P < 0.001). Markers of bone turnover were significantly elevated in patients post LRGB compared with controls (urinary N-telopeptide cross-linked collagen type 1, 93 +/- 38 vs. 24 +/- 11 nmol bone collagen equivalents per mmol creatinine; and osteocalcin, 11.6 +/- 3.4 vs. 7.6 +/- 3.6 ng/ml; both P < 0.001). Fifteen patients were studied prospectively for an average of 9 months after LRGB. They lost 37 +/- 9 kg and had a 29 +/- 8% fall in body mass index (both P < 0.001). Urinary N-telopeptide cross-linked collagen type 1 increased by 174 +/- 168% at 3 months (P < 0.01) and 319 +/- 187% at 9 months (P < 0.01). Bone mineral density decreased significantly at the total hip (7.8 +/- 4.8%; P < 0.001), trochanter (9.3 +/- 5.7%; P < 0.001), and total body (1.6 +/- 2.0%; P < 0.05), with significant decreases in bone mineral content at these sites. In summary, within 3 to 9 months after LRGB, morbidly obese patients have an increase in bone resorption associated with a decrease in bone mass. Additional studies are needed to examine these findings over the longer term.