Calcium bioavailability in relation to bone health

A well established stable isotope technique exists for measuring calcium absorption from single foods and meals, but the long term effects of calcium on bone health cannot be assessed from acute bioavailability studies. Bone health depends primarily on the degree of mineralization, measured as bone mineral density (BMD), and phenotypic variations depend on genetic and environmental factors including calcium supply. Since almost all retained calcium is used for bone mineralization and remodeling, BMD can be used as a long-term (> six months) marker of dietary calcium bioavailability. However, BMD is a very insensitive marker of calcium bioavailability, so its use in dietary intervention studies is restricted to periods of significant bone growth or loss. Biochemical markers of bone metabolism may be used to predict the overall bioavailability of dietary calcium over a shorter time period (> four weeks), but they have a high coefficient of variation, so may not be appropriate for some dietary intervention studies. A group of European laboratories is currently developing an alternative approach using a long-lived radioisotope (41Ca) to label bone calcium and to directly measure the rate of calcium loss from urinary excretion data. The efficiency of calcium absorption is inversely related to intake; whole body balance of the mineral is dependent on rates of absorption and excretion and limited by calcium-binding substances in the gut. Dietary data and indirect measures of bone health indicate that bioavailability is important when habitual intakes are low, especially during periods of bone growth or loss. Further research is required to quantify the effects of major dietary modulators of calcium balance on bone health and to understand their relationship with genetic and physiological variables.     

乳糖不耐受与钙摄取和骨健康研究进展

乳糖不耐受被认为与钙摄取和骨健康息息相关。目前普遍认为乳糖不耐受会降低钙摄入量,但对于钙吸收率的影响至今仍有较大的争议。在乳糖不耐受人群中,乳糖可能是影响钙吸收的重要因素,而早期研究设计中的不同乳糖剂量负荷也可能是导致不同结果的原因。而近十几年的研究发现乳糖酶相关基因类型是影响钙摄入与骨健康的重要因子。然而既往研究受限于知识技术的限制,研究内与研究间的异质性过大,这导致了相关研究出现相互矛盾的数据聚集。这也迫使当下进行更可靠的大样本对照研究来探讨乳糖不耐受与钙摄取和骨健康的相关性。     

Protein intake, calcium balance and health consequences

High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.     

Calcium bioavailability from calcium fortified food products.

The calcium balance of 12 presumed healthy human young adult subjects was assessed. Subjects consumed a constant laboratory-controlled diet supplemented with one of four calcium-fortified food products: orange juice (OJ), milk (M), experimental pasteurized processed cheese (T), soda (S), or a calcium carbonate plus vitamin D tablet (CC). Study length was 6 weeks with seven-day experimental periods (2-days allowed for adjustment with 5-days combined for purposes of analysis). All urine and fecal samples were collected by the subjects for the duration of the study. Blood samples were drawn at the end of each experimental period. Urine and fecal calcium contents were determined. Blood samples were analyzed for alkaline phosphatase. Results of this study indicate a higher fecal calcium content (mg/day) when subjects consumed CC and T, and when subjects consumed self-selected diets, than when given S, M, or OJ. Urinary calcium excretion was significantly lower when subjects consumed OJ than when they consumed M, T, or their self-selected diets. A significantly larger positive calcium balance was demonstrated when subjects consumed OJ as compared to T. Fecal transmit time did not vary significantly. Serum alkaline phosphatase was significantly lower when subjects consumed T than when they consumed self-selected diets.     

Protein intake and bone health

Adequate nutrition plays an important role in the development and maintenance of bone structures resistant to usual mechanical stresses. In addition to calcium in the presence of an adequate supply of vitamin D, dietary proteins represent key nutrients for bone health and thereby function in the prevention of osteoporosis. Several studies point to a positive effect of high protein intake on bone mineral density or content. This fact is associated with a significant reduction in hip fracture incidence, as recorded in a large prospective study carried out in a homogeneous cohort of postmenopausal women. Low protein intake (< 0.8 g/kg body weight/day) is often observed in patients with hip fractures and an intervention study indicates that following orthopedic management, protein supplementation attenuates post-fracture bone loss, tends to increase muscle strength, and reduces medical complications and rehabilitation hospital stay. There is no evidence that high protein intake per se would be detrimental for bone mass and strength. Nevertheless, it appears reasonable to avoid very high protein diets (i. e. more than 2.0 g/kg body weight/day) when associated with low calcium intake (i. e. less than 600 mg/day). In the elderly, taking into account the attenuated anabolic response to dietary protein with ageing, there is concern that the current dietary protein recommended allowance (RDA), as set at 0.8 g/kg body weight/day, might be too low for the primary and secondary prevention of fragility fractures.     

Flavonoid intake and bone health

Flavonoids, found in a wide diversity of plant foods from fruits and vegetables, herbs and spices, essential oils, and beverages, have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D. Recent epidemiological studies show flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption. Bioactive flavonoids are being assessed for properties beyond their chemical antioxidant capacity, including anti-inflammatory actions. Some have been reported to enhance bone formation and to inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation. Future research is needed to determine which of the flavonoids and their metabolites are most effective and at what dose, as well as the mechanism of modulating cellular events, in order to set priorities for clinical trials.     

Dietary calcium intake, vitamin D status, and bone health in postmenopausal women in rural Pakistan

The high prevalence of osteoporosis in Pakistan is of public-health concern. However, there is a paucity of information regarding nutrition and bone density in rural communities. The purpose of this study was to evaluate the dietary and lifestyle factors that impact bone health in Nahaqi. Data were collected from 140 postmenopausal women using an interviewer-administered 24-hour dietary recall questionnaire. Bone mineral density was estimated using the quantitative ultrasound index (QUI). Serum 25(OH)D was measured in fasting blood samples. The QUI scores revealed that 42% and 29% of the women had T-scores, indicative of osteopaenia and osteoporosis respectively. The mean calcium intake was 346 mg/d, which is less than 50% of the recommended daily intake. The QUI correlated with 25(OH)D after controlling for age (p=0.021, r=0.41, r2=0.168). Vitamin D deficiency and low intake of dietary calcium are two key factors contributing to poor bone health in this population.     

Calcium intake, physical activity and bone mass in pre-menopausal women

Thirty pre-menopausal women aged 35–40 years were assessed with respect to dietary calcium intake, physical activity and other factors related to bone loss (by questionnaire); bone mass in the mid and distal femur measured by computerized tomography; and leg strength and muscle size. Cortical thickness at mid-femur was negatively associated with breast-feeding (r=-0.40). Bone mass in the distal femur was negatively associated with age (r=-0.46) and positively associated with activity (r=0.44) and leg strength (r=0.42). There was no association of bone mass at either site with current dietary calcium intake (range 198–1511 mg/day), nor with body mass index (BMI), hand-grip strength, parity, oral contraceptive use, smoking, or alcohol intake. Thus, in older pre-menopausal women, activity apparently helps to maintain bone mass at the distal femur, a site of high trabecular bone content, while current dietary-calcium intake has no effect on bone mass in the femur. Activity was most strongly associated with bone mass in the distal femur when it was defined as the total number of hours spent standing or moving (i.e. other than sitting or lying down), regardless of the intensity of activity.
The strong negative association between bone mass in the distal femur and age in older pre-menopausal women is of concern in relation to long-term risk of osteoporotic related fracture, suggesting that factors relating to bone loss in this age-group should be studied longitudinally. The apparent loss of cortical bone in breast-feeders warrants further investigation.     

Calcium and protein in bone health

Dietary protein has several opposing effects on Ca balance and its net effect on bone is not well established. It has long been recognized that increasing protein intake increases urinary Ca excretion. More recently, it has been observed that increasing dietary protein raises the circulating level of insulin-like growth factor-1, a growth factor that promotes osteoblast formation and bone growth. Other effects of protein on the Ca economy have been suggested in some studies, but they are less well established. Several studies have examined associations between protein intake and bone loss and fracture rates. In the original Framingham cohort subjects with lower total and animal protein intakes had greater rates of bone loss from the femoral neck and spine than subjects consuming more protein. In another study higher total (and animal) protein intakes were associated with a reduced incidence of hip fractures in post-menopausal women. In contrast, a high animal:plant protein intake has been associated with greater bone loss from the femoral neck and a greater risk of hip fracture in older women. Higher total and higher animal protein intakes have also been associated with increased risk of forearm fracture in younger post-menopausal women. In a recent study it was found that increasing dietary protein was associated with a favourable (positive) change in bone mineral density of the femoral neck and total body in subjects taking supplemental calcium citrate malate with vitamin D, but not in those taking placebo. The possibility that Ca intake may influence the impact of dietary protein on the skeleton warrants further investigation.     

Calcium and bone health of women

The calcium content of a 2400 kcal Canadian diet patterned after the Nutrition Canada Food Consumption Patterns Report (1977) was found to be 900 mg and the phosphorus content was 1280 mg. Milk and dairy products provided 64% of the calcium and only 33% of the phosphorus. An examination of the calcium intake of females in different age groups revealed that about 25% of those 10 yr and older had less than 60% of the recommended intake. In the U.S. the results of HANES 1 (1971–74) were similar. In HANES 2 (1976–80) also, the average calcium intakes of females over 14 yr were 60 to 70% of the recommended intakes. The median daily calcium intake of 30 to 65 yr old Belgian women was reported to be 540 mg, which was two-thirds of the recommendation. Although the distribution of phosphorus intakes is not known, the average amount in the diets of Canadian females was up to 1.5 times the calcium content. The amount of calcium in the Canadian food supply did not change appreciably from 1970 to 1983. Although an excess of dietary phosphorus in relation to calcium does not adversely affect absorption of calcium, it has been reported that habitual consumption of a diet with a low Ca:P ratio is detrimental to bone density in women, especially when calcium intake is suboptimal. Recent reports indicate that a low calcium intake in suboptimal. Recent reports indicate that a low calcium intake in adolescence and early adulthood does not provide for optimal consolidation of bone and results in a relatively low bone mass in the premenopausal period. This can be an important risk factor in the development of postmenopausal osteoporosis. Vertebral bone density was reported to be higher in 24–5 yr old women who had high calcium intakes (755 mg or more/day) and high physical activity than in those who had lower calcium intakes and were less active. Since the evidence for the efficacy of calcium supplements in the treatment of postmenopausal osteoporosis is not consistent, the best approach appears to be prevention by ensuring optimal calcium and vitamin D nutrition throughout the life span, adequate physical activity; and by avoiding heavy smoking, high consumption of alcohol and caffeine.     

Calcium intake trends and health consequences from childhood through adulthood

Issues involving low calcium intake and dairy product consumption are currently the focus of much debate and discussion at both the scientific and lay community levels. In this review, we examine the following major areas of interest: (1). the role of calcium intake and dairy product consumption in chronic diseases, (2). nutritional qualities of milk and other dairy products, (3). trends in calcium intake and dairy product consumption, (4). current status of calcium intakes and dairy product consumption in children, (5). tracking of calcium intake and diary product consumption, (6). the impact of school meal participation on calcium intake and dairy product consumption, (7). concerns related to calcium-fortified foods and beverages and (8). factors influencing children's milk consumption. To date, the findings indicate that calcium intake and dairy product consumption have beneficial roles in a variety of chronic diseases; dairy products provide an abundant source of vitamins and minerals; calcium intakes of children have increased over time, yet intakes are not meeting the current adequate intake (AI) calcium recommendations; dairy consumption has decreased, and soft drink consumption and, possibly, consumption of calcium-fortified products have increased; consumption of dairy products have a positive nutritional impact on diets of children, particularly from school meals, and there are many factors which influence children's milk consumption, all of which need to be considered in our efforts to promote adequate calcium intakes by children. Based on this review, areas that need immediate attention and future research imperatives are summarized in an effort to further our understanding on what we already know and what we need to know to promote healthier eating habits early in life.     

Children's bone health and meeting calcium needs

One in two women and one in five men suffer from osteoporotic fractures after the age of 50. Enabling children and young people to develop strong bones and achieve their maximum potential bone mass will help prevent undue bone loss and osteoporosis in later life. Although 70-80% of peak bone mass is genetically determined, the remainder is determined by dietary and environmental factors. The most important dietary factor for bone health is calcium, which in the UK is obtained mainly from dairy foods (45%) and cereal-based foods (27%). In the UK one-quarter of teenage girls consume insufficient calcium to meet their minimum dietary requirements. The majority of teenage boys and girls fail to meet the UK Government's targets for calcium intakes. This is an important public health issue as 90% of peak bone mass is attained by the age of approximately 18 years in girls and 20 years in boys. Health professionals need to be aware of the importance of childhood and adolescence for building healthy bones and to work with this age group to promote the dietary and lifestyle factors that contribute to bone health and peak bone mass. They could usefully include advice on including three helpings of calcium in the diet each day, as highlighted in the current "3-a-Day" campaign.     

Calcium intake and bone mass development among Israeli adolescent girls.

OBJECTIVE: To determine the possible relationship between food and life style habits and bone health in adolescent Israeli females. METHODS: 2,000 adolescent Israeli Jewish and Arab high-school girls (mean age 14.5) completed a semi-quantitative food frequency questionnaire and a personal history questionnaire. 27 food components were calculated for each subject. Bone mineral content and density were determined for 112 subjects with calcium intake below 800 mg/day. RESULTS: Average calcium intake was found to be 1,260 mg/day, but 20% of all girls had a calcium intake below 800 mg/day. All low-energy diets were very low in calcium, as mean calcium intake per 1,000 calories was 411 128 grams. A large percentage of diets with less than 800 mg calcium were also deficient in phosphorus (95.2%), magnesium (84.8%). iron (90.5%) and zinc (100%). Due to differences in food sources. Jewish girls had more phosphorus in their diet, but less magnesium and iron compared to Arab girls. Calcium and zinc deficiencies in Jewish and Arab diets were similar. A negative correlation was found between body mass index (BMI) and age at menarche for all girls in the study. Bone mineral density (BMD) measured for girls with calcium intake below 800 mg/day distributed normally around the average when compared to age matched controls despite their low calcium intake. There was a strong positive correlation between BMD and bone mineral content (BMC) at all sites and body weights. CONCLUSIONS: Low calcium intake, other nutritional deficiencies and delayed menarche due to low-energy diet in the growing period and in adolescence may prevent the formation of healthy bones. There is no evidence of lower bone mass among the low calcium intake group in the study population at this stage. It remains to be documented if the window of opportunity for optimal bone accretion for this group will be missed in the future. possibly leading to increased risk of osteoporosis.     

Spinal bone density and calcium intake in healthy postmenopausal women

Dietary calcium intake and bone mineral density (BMD) of the lumbar spine (L2-L4) were determined in 131 healthy free-living postmenopausal women (aged 64.7 +/- 7.6 y, means +/- SD). The calcium consumption for the total population was 606 +/- 302 mg/d. Subjects consuming less than the population mean of dietary calcium had significantly lower BMDs than did subjects with intakes above the mean (P less than 0.009); these two groups did not differ in basic demographic characteristics. Additional analyses using a stepwise univariate regression model demonstrated that BMD was significantly associated with body weight (P less than 0.001) and dietary calcium intake (P less than 0.02). These data support the hypothesis that dietary calcium intake is a determinant of skeletal health in postmenopausal women.     

Lactose, calcium source and age affect calcium bioavailability in rats

Calcium bioavailability was defined as either retention of 45Ca in tibias (Experiment 1) or retention of 47Ca in carcasses (Experiment 2). In Experiment 1, rats (age 21, 40 or 100 d) were fed purified meals extrinsically labeled with 45Ca. The meals contained either 0.5% Ca (control) or 1% Ca [control supplemented with CaCO3, calcium citrate-malate (CCM), milk or cheese] and either no lactose or 20% lactose. Lactose increased Ca bioavailability (P less than 0.05) from the control and milk meals in all age groups. Increases from CCM and CaCO3 were significantly only in the 21-d-old group. Lactose did not affect bioavailability from cheese. In Experiment 2, suckling rats (age 7, 12 or 17 d) were gavaged with 47Ca-labeled milk (fluid skim or lactose-hydrolyzed fluid skim) or an aqueous CaCl2-casein mixture (containing either no sugar, glucose + galactose, or lactose). Bioavailability from milk was higher than from lactose-hydrolyzed milk in all age groups. Lactose and glucose + galactose increased bioavailability over the sugar-free CaCl2-casein mixture in all age groups. Data from these experiments show that lactose enhances Ca bioavailability at several stages of development and the effect is not markedly diminished by high Ca diets. Lactose increases Ca bioavailability from a variety of sources but the magnitude of the effect may vary among sources.     

Self-reported calcium intake and bone mineral content in children and adolescents

OBJECTIVE: We examined the relationship between self-reported calcium (Ca) intake and bone mineral content (BMC) in children and adolescents. We hypothesized that an expression of Ca adjusted for energy intake (EI), i.e., Ca density, would be a better predictor of BMC than unadjusted Ca because of underreporting of EI. METHODS: Data were obtained on dietary intakes (repeated 24-hour recalls) and BMC (by DEXA) in a cross-section of 227 children aged 8 to 17 years. Bivariate and multivariate analyses were used to examine the relationship between Ca. Ca density, and the dependent variables total body BMC and lumbar spine BMC. Covariates included were height, weight, bone area. maturity age, activity score and EI. RESULTS: Reported EI compared to estimated basal metabolic rate suggested underreporting of EI. Total body and lumbar spine BMC were significantly associated with EI, but not Ca or Ca density, in bivariate analyses. After controlling for size and maturity, multiple linear regression analysis revealed unadjusted Ca to be a predictor of BMC in males in the total body (p = 0.08) and lumbar spine (p = 0.01)). Unadjusted Ca was not a predictor of BMC at either site in females. Ca density was not a better predictor of BMC at either site in males or females. CONCLUSIONS: The relationship observed in male adolescents in this study between Ca intake and BMC is similar to that seen in clinical trials. Ca density did not enable us to see a relationship between Ca intake and BMC in females, which may reflect systematic reporting errors or that diet is not a limiting factor in this group of healthy adolescents.     

Calcium intake and adiposity

Limited epidemiologic and experimental data support the possibility that dietary calcium intake plays a role in human body weight regulation. The aim of this review was to present the data from human studies that link calcium and dairy intake to body weight, describe the existing evidence for an effect of calcium intake on body weight from animal models of obesity, present evidence of a role for intracellular calcium in the regulation of lipogenesis and lipolysis, elucidate the potential suggested relation between dietary calcium intake and intracellular calcium concentrations, and outline the effects of calcium supplementation on dietary fat absorption. We suggest that these data support the need for large, population based clinical trials to assess the effects of supplemental calcium and other components of dairy products on human body weight.