Associations of vitamin D receptor, calcium-sensing receptor and parathyroid hormone gene polymorphisms with calcium homeostasis and peripheral bone density in adult Finns.

BACKGROUND: Thus far the search for osteoporosis candidate genes has focused less attention on the regulation of calcium homeostasis. Associations of vitamin D receptor (VDR) FokI, calcium-sensing receptor (CaSR) A986S and parathyroid hormone (PTH) BstBI polymorphisms with calcium homeostasis and peripheral bone density were investigated in adult Finns. METHODS: The subgroup of the population-based FINRISK survey consists of 339 healthy adults aged 31-43 years. Lifestyle data were assessed with questionnaires and food diaries. DNA was isolated from blood, and biochemical determinants of calcium metabolism were measured from blood and 24-hour urine samples. Bone mineral density (BMD) was measured using the DXA method at the distal forearm and by quantitative ultrasound (broadband ultrasound attenuation and speed of sound) at the calcaneus. Subjects were genotyped for VDR FokI, CaSR A986S and PTH BstBI polymorphisms. RESULTS: The CaSR 986S allele was associated with higher serum ionized calcium (p = 0.014). Forearm BMD was lowest for the PTH BstBI genotype bb in males (p = 0.023). VDR FokI and PTH BstBI polymorphisms showed a significant interaction on serum PTH (p = 0.010). The other gene-gene or diet-gene interactions studied showed no significant results. CONCLUSIONS: VDR, CaSR and PTH contribute to the genetic regulation of calcium homeostasis and peripheral bone density.

Acute effects of different phosphorus sources on calcium and bone metabolism in young women: a whole-foods approach.

The recommended dietary phosphorus intake is exceeded in the typical Western diet. However, few studies have been conducted on the bioavailability and metabolic consequences of dietary phosphorus from different food sources. In this study, acute effects of dietary phosphorus from three different food sources and a phosphate supplement on calcium and bone metabolism were investigated. Sixteen healthy women aged 20-30 years were randomized to five controlled 24-hour study sessions, each subject serving as her own control. At the control session, calcium intake was ca. 250 mg and phosphorus intake ca. 500 mg. During the other four sessions, phosphorus intake was about 1,500 mg, 1,000 mg of which was obtained from meat, cheese, whole grains, or a phosphate supplement, respectively. The foods served were exactly the same during the phosphorus sessions and the control session; only phosphorus sources varied. Markers of calcium and bone metabolism were followed. Analysis of variance with repeated measures was used to compare the study sessions. Only the phosphate supplement increased serum parathyroid hormone (S-PTH) concentration compared with the control session (P = 0.031). Relative to the control session, meat increased markers of both bone formation (P = 0.045) and bone resorption (P = 0.049). Cheese decreased S-PTH (P = 0.0001) and bone resorption (P = 0.008). These data suggest that the metabolic response was different for different foods.

A 7-week reduction in salt intake does not contribute to markers of bone metabolism in young healthy subjects.

BACKGROUND: Sodium intake increases urinary calcium excretion and may thus lead to negative calcium balance and bone loss. OBJECTIVE: We hypothesised that reducing sodium intake would reduce urinary calcium excretion and have a beneficial influence in bone metabolism. DESIGN: A total of 29 subjects, 14 males and 15 females, were divided into two study groups. One group (low-sodium group (LS)) reduced sodium intake for 7 weeks by substituting low-salt alternatives for the most important dietary sources of sodium. The other group, serving as a control group (C), was given the same food items in the form of normally salted alternatives. Fasting serum samples as well as 24-h urine samples were obtained in the beginning and at the end of the study. Urinary sodium, urinary calcium, urinary creatinine, serum calcium, serum phosphate, serum creatinine, serum parathyroid hormone (s-PTH), serum C-terminal telopeptides of Type-I collagen and serum bone alkaline phosphatase (s-B-ALP) were analysed. RESULTS: The LS group showed a significant decline (P = 0.001) in urinary sodium/creatinine ratio without a significant effect on urinary calcium/creatinine ratio. In the LS group, s-PTH increased (P = 0.03). The C group showed an increase in s-PTH (P = 0.05) and in s-B-ALP, but no differences were observed between the study groups in the changes of serum markers of calcium and bone metabolism. CONCLUSIONS: We have shown that reducing the sodium intake of young, healthy people with adequate calcium intake over a 7-week period does not affect the markers of bone metabolism.

Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe?

A low vitamin D status could be a concern not only in children and the elderly in Europe, but also in adults. We do not know the effect of mild vitamin D deficiency on bone in this age group. The aim of this study was to detect the prevalence of low serum 25-hydroxyvitamin D [S-25(OH)D] and elevated serum intact parathyroid hormone (S-iPTH) concentrations in healthy young adults in the winter in northern Europe and to characterize the determinants of these variables. In addition, we studied the association between vitamin D status and forearm bone mineral density (BMD) in this population group. Three hundred and twenty-eight healthy adults (202 women and 126 men, 31-43 years) from southern Finland (60 degrees N) participated in this study conducted in February through March 1998. Fasting overnight blood samples were collected in the morning. Forearm BMD was measured by dual-energy X-ray absorptiometry (DXA). The mean daily vitamin D intake met the recommendations in the men (5.6 +/- 3.2 microg) and almost met it in the women (4.7 +/- 2.5 microg). The mean S-25(OH)D concentrations did not differ between genders (women, 47 +/- 34 nM; men, 45 +/- 35 nM; mean +/- SD), but the women had significantly higher mean S-iPTH levels than the men (women, 30 +/- 13 ng/liter; men, 24 +/- 12 ng/liter; p < 0.001). Low S-25(OH)D concentrations (<25 nM) were found in 26.2% of the women (53 women) and 28.6% of the men (36 men), respectively. Based on nonlinear regression analysis between S-25(OH)D and S-iPTH concentration, the S-iPTH concentration started to increase with S-25(OH)D concentrations lower than approximately 80 nM in the women and lower than approximately 40 nM in the men. Based on this relation between S-25(OH)D and S-iPTH concentrations, 86% of the women and 56% of the men had an insufficient vitamin D status. In linear regression analysis, the main positive determinants of S-25(OH)D were dietary vitamin D intake (p < 0.02), the use of supplements (p < 0.005), alcohol intake (p < 0.05), and age (p < 0.005). Smoking associated negatively with the S-25(OH)D concentration (p < 0.03). The main determinants of S-iPTH were S-25(OH)D (p < 0.01), dietary calcium intake (p < 0.02), and body mass index (BMI; p < 0.01). In addition, female gender was associated with higher S-iPTH concentration. The mean daily dietary calcium intake was 1,037 +/- 489 mg and 962 +/- 423 mg, in the men and women, respectively. Significantly lower forearm BMD was found in the men (p = 0.01) but not in the women (p = 0.14) with higher S-iPTH concentrations. Low vitamin D status was prevalent in these young adults in northern Europe in winter, although the vitamin D intake met the recommendation. This probably is not a local problem for northern Europe, because the natural sources of vitamin D are scarce and fortification is not very common in Europe, and with the exception of the southern part of Europe, sunshine is not very abundant in this part of the world. Thus, the results of this study indicate that more attention should be focused on vitamin D status and the sources of vitamin D in these countries.

Does it make a difference how and when you take your calcium? The acute effects of calcium on calcium and bone metabolism.

BACKGROUND: Calcium supplements are widely used to prevent osteoporosis. However, little is known about the metabolic effects of different dosages and of the timing of the dosages. OBJECTIVE: The aim was to study the effects of the timing of the dose (study 1), the effects of the size of the dose (study 2), and the effects of small repetitive doses (study 3) of calcium on calcium and bone metabolism in women. DESIGN: The investigation was conducted in 3 parts, each with 10 participants. In study 1, calcium loads (0 and 25 mg/kg body wt) were taken at 0900 and 2100. In study 2, calcium loads of 0, 250, and 1000 mg were taken at 0900. In study 3, calcium loads of 0 and 200 mg were taken 4 times/d. Markers of calcium and bone metabolism were followed. RESULTS: There was no significant difference in the response of serum parathyroid hormone (PTH) to the calcium load taken at 0900 and that at 2100. There was a significant dose-response effect of the calcium load on serum ionized calcium (P = 0.00005) and serum PTH (P = 0.0003). Small calcium doses (200 mg) taken 4 times/d kept the PTH secretion at a lower level than during the control day (P = 0.016). None of the doses caused significant changes in the markers of bone formation and resorption measured. CONCLUSIONS: The calcium loads had no significant effect on the markers of bone formation and resorption measured, although even small calcium doses decreased serum PTH and increased serum ionized calcium concentrations rapidly. The effect was similar whether calcium was taken in the morning or in the evening.

Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density.

BACKGROUND: Vitamin D deficiency leads to secondary hyperparathyroidism, which has a negative effect on bone metabolism in the elderly. Puberty is an important time of bone metabolism and growth. The effect of serum 25-hydroxyvitamin D [25(OH)D] concentrations on parathyroid hormone concentrations and bone mineral density (BMD) has not been well studied cross-sectionally in adolescents. OBJECTIVE: We studied the effect of vitamin D status on serum intact parathyroid hormone (iPTH) concentrations and bone metabolism in adolescents. DESIGN: One hundred seventy-eight healthy female adolescents (aged 14-16 y) volunteered for this study, which was conducted in Finland (Helsinki, 60 degrees N) during the winter. Forearm BMD at radial and ulnar sites was measured by dual energy X-ray absorptiometry. The determinants of different variables were studied by use of regression models. RESULTS: On the basis of the relation between serum 25(OH)D and iPTH concentrations, serum 25(OH)D concentrations > approximately 40 nmol/L were needed to keep serum iPTH concentrations low. One hundred ten subjects (61.8%) had serum 25(OH)D concentrations < or =40 nmol/L. Twenty-four subjects (13.5%) were considered vitamin D deficient when the serum 25(OH)D concentration of 25 nmol/L was used as a cutoff. Subjects with serum 25(OH)D concentrations < or =40 nmol/L had low mean forearm BMD values at both the radial (P = 0.04) and ulnar (P = 0.08) sites. CONCLUSION: A large percentage of adolescent females have low vitamin D status during the winter in Finland, which seems to have negative effects on bone health.

Enhancing the capacity of food consumption surveys of short duration to estimate long-term consumer-only intakes by combination with a qualitative food frequency questionnaire.

In principle, a proper risk assessment for a food chemical requires that the time-frame for food chemical intake estimates matches the time-frame for the toxicological assessments upon which the safety statements (ADI, PTWI, etc.) are based. For food additives, the toxicological assessments are based on exposure over a lifetime. While food consumption data cannot be collected over the lifetimes of individuals, the information should reflect habitual intakes as closely as possible. This study investigated the possibility of combining a 3-day food diary with a food frequency questionnaire to estimate mean consumer-only food intakes comparable to estimates based on a 14-day diary. The study population consisted of 948 teenagers and analysis was based on 32 clearly defined foods. For 47% of the foods, the difference was < or = 1 g/day. When expressed as portion sizes, 56% of the foods showed differences representing < 5% of an average portion and no food showed a difference > 14% of an average portion. When between-method differences (portions/day) were plotted against the mean of the methods, the mean between-method difference was 0.02(+/- 0.06) portions/day with limits of agreement of -0.10 to 0.14. This preliminary investigation suggests that the combined 3-day diary and FFQ method provides comparable estimates of mean consumer only intakes to a 14-day diary. Therefore, a qualitative FFQ may be a useful adjunct to a food consumption survey of short duration if estimates of longer term food intakes are required.

Dietary intake of vitamin D in premenopausal, healthy vegans was insufficient to maintain concentrations of serum 25-hydroxyvitamin D and intact parathyroid hormone within normal ranges during the winter in Finland.

OBJECTIVE: To study vitamin D status and bone metabolism of premenopausal vegetarians and omnivores during a 1-year period. DESIGN: Longitudinal, observational study. Bone mineral density was measured, blood samples from fasting subjects were obtained, and 24-hour urinary samples were collected in February 1994, August 1994, and January 1995. Serum 25-hydroxyvitamin D [S-25(OH)D] and intact parathyroid hormone (S-iPTH) concentrations were measured and intestinal calcium absorption was estimated. Dietary intakes of vitamin D and calcium were calculated. SUBJECTS/SETTING: Six vegans, 6 lactovegetarians, and 16 omnivores living in Helsinki, Finland. STATISTICAL ANALYSES PERFORMED: Student-Newman-Keuls test; unbalanced, repeated-measures multiple analysis of variance; analysis of covariance; Pearson correlation test; and linear regression analysis. RESULTS: Dietary intake of vitamin D was significantly lower in vegans (P < .05, yearly mean +/- standard deviation = 0.09 +/- 0.06 microgram/day) and in lactovegetarians (P < .05, 0.7 +/- 0.4 microgram/day) compared with omnivores (4.0 +/- 2.1 micrograms/day). Throughout the year S-25(OH)D (P = .01) concentrations were lower and S-iPTH (P = .01) concentrations were higher in vegans than in omnivores and lactovegetarians. Bone mineral density in the lumbar region of the spine was lower in vegans (yearly mean +/- standard deviation = 1.034 +/- 0.174 g/cm2) than in omnivores (P = .05, 1.177 +/- 0.099 g/cm2) and tended to be lower than that in lactovegetarians (P = .17, 1.138 +/- 0.06 g/cm2). Bone mineral density in the neck of the femur tended to be lower in vegans (0.843 +/- 0.116 g/cm2) than in omnivores (P = .07, 0.999 +/- 0.138 g/cm2) and lactovegetarians (P = .15, 0.961 +/- 0.059 g/cm2). No seasonal variation was found in bone mineral density in the study groups. CONCLUSIONS: At northern latitudes, dietary intake of vitamin D in vegans was insufficient to maintain S-25(OH)D and S-iPTH concentrations within normal ranges in the winter, which seems to have negative effects on bone mineral density in the long run. APPLICATIONS: An increase in vitamin D intake should generally be recommended for vegans at least during winter, or selections of foodstuffs fortified with vitamin D should be broadened in northern latitudes.

Postprandial parathyroid hormone response to four calcium-rich foodstuffs.

We studied the effects of four calcium-rich foodstuffs on postprandial parathyroid hormone secretion. Four hundred milligrams calcium from either Emmental cheese, milk, sesame seeds, spinach, or calcium salt (calcium lactate gluconate + calcium carbonate) or no additional calcium (control session) were given to nine female volunteers immediately after a first blood sample (at 0900) in random order with a light standardized meal containing 37 mg Ca. Blood samples were taken at 0900 (before the calcium load), 1000, 1100, 1300, and 1500 at every study session. Urine was collected during the sessions. Serum ionized calcium, phosphate, magnesium, intact parathyroid hormone, and urinary calcium excretion were measured. The serum ionized calcium concentration increased significantly after ingesting cheese (P = 0.004, contrast analysis) or calcium salt (P = 0.05, contrast analysis) compared with the control session. Compared with the control session, the serum phosphate concentration increased after the cheese session (P = 0.004, contrast analysis) and after the milk session (P = 0.02, contrast analysis). Calcium salt (P = 0.007, contrast analysis) and cheese (P = 0.002, contrast analysis) caused a significant decline in serum intact parathyroid hormone compared with the control session. The urinary calcium excretion with cheese was 141% (P = 0.001), with milk was 107% (P = 0.004), and with calcium salt was 75% (P = 0.02) above that of the control session. Our results show that calcium from sesame seeds and spinach does not cause an acute response in calcium metabolism. Our results indicate that fermented cheese could be a better dietary source of calcium than milk when the metabolic effects of the foodstuffs are considered.