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Optimal nutrition towards osteoporosis prevention:Impact of diet and gene-nutrient interactions on calcium and bone metabolism

Project Code: N05025

30/10/2003

Institute of Food Research Enterprises Ltd
Teucher, B ; Spinks, C; Dainty, J; Majsak-Newman, G; Berry, D; Fairweather-Tait, S; Foxall, R

Background

Osteoporosis is a growing problem in the UK, thus it is important to devise public health strategies to enhance bone health. Although diet is acknowledged to play a significant role in increasing or reducing the risk of osteoporosis, an in-depth understanding of dietary factors is lacking. The level of salt (sodium chloride) intake is high in the UK and it is thought that this may contribute to the risk of osteoporosis through sodium-induced increases in obligatory urinary calcium loss (calciuria). When combined with a low calcium intake, it is likely that calcium balance will be negative, thereby leading to bone depletion.

The data from cross-sectional and longitudinal prospective studies on salt reduction in relation to BMD are inconsistent and not helped by the lack of long-term randomised controlled trials. Therefore, evidence for a detrimental effect of high salt intake on bone health is primarily limited to short-term effects of sodium on calcium metabolism. Inconsistencies in results from such studies with calcium absorption and bone turnover as endpoints do not lend support to the hypothesis that high salt intakes typically consumed by a large proportion of the UK population are associated with an increased rate of bone loss (Teucher and Fairweather-Tait, 2003).

In the past, limited attention has been paid to other dietary components such as protein, phosphorus and potassium and/or fruits and vegetables that may modulate the effect of sodium on calcium balance. Taking these dietary factors into consideration is crucial for a full characterization of salt as a risk factor for osteoporosis especially in relation to dietary pattern of specific populations and groups within populations. Considering the difficulties associated with the generation of longitudinal data in relation to salt intake and bone health, clearly, our understanding of salt as a long-term risk factor of osteoporosis will benefit from further investigation of the adaptive mechanisms determining calcium absorption excretion, and bone calcium metabolism.

Rationale and Objectives

Urinary calcium losses may be offset by adaptive changes in calcium absorption and/or the rate of bone resorption. If there is no up-regulation of absorption, and no decrease in bone resorption, prolonged habitual high salt intake will undoubtedly increase the risk of osteoporosis. To date, there are no indisputable consistent bone biomarker or longitudinal data describing changes in BMD or fracture risk as outcome measure in relation to salt intake (Teucher and Fairweather-Tait, 2003). Even less attention has been paid to the study of calcium balance. Whether up-regulation of calcium absorption may compensate partly or even fully for sodiuminduced urinary calcium losses has not been conclusively demonstrated. The present project was devised to investigate the extent to which sodium-induced calciuria can be compensated for by
changes in the efficiency of calcium absorption in postmenopausal women, and the modifying effect of calcium intake. Further objectives were the assessment of endogenous faecal calcium excretion, bone turnover and calcium kinetics in response to dietary intervention.

Approach

Twenty postmenopausal women were recruited to participate in a randomised cross-over trial consisting of four successive periods of controlled dietary intervention of four weeks each, followed by a minimum 4 week washout during which time subjects consumed their habitual diet. Eleven subjects completed all four dietary interventions, three subjects completed 2 interventions and a further two subjects completed 3 interventions. A number of exclusion criteria were applied including moderate to high blood pressure (i.e. > 140/90 mmHg), chronic disease, bone disease and hormone replacement therapy. For the safety of the subjects blood pressure was monitored throughout the dietary intervention trial.

The longitudinal nature of the trial required that subjects were supplemented with vitamin D to avoid any seasonal variation in 25(OH)D that may affect study outcome. A 7-day rotating menu was devised and the calcium and sodium content was confirmed by chemical analysis. Subjects were provided with all food consumed during each of the four dietary interventions. All four diets were identical except for the level of calcium and sodium which was adjusted via the intake of calcium carbonate and/or salt supplements. The level of calcium (500mg versus 1250mg) and salt intake (3.6g versus 9.6g) was similar to that commonly consumed by a significant percentage of UK women confirming the relevance of this investigation to the UK dietary habits of this age group.

The present study employed state-of-the-art calcium stable isotope labelling techniques to determine calcium absorption and excretion and a compartmental model was fitted to the data to predict bone calcium balance. Bone biomarkers for the assessment of bone turnover and calcitropic hormones were determined at the start and end of each of the four dietary interventions.

Key Results and Conclusions

· The mean 25(OH)D concentration of subjects was consistent over the length of the intervention, above the reference point for vitamin D insufficiency, and mostly likely representative of levels encountered during the UK summer period. In the present study, there was no effect of the high/low calcium and sodium combination diets on the regulators of the adaptive mechanisms of calcium homeostasis, i.e. serum 25(OHD), 1,25 (OH)D, and parathyroid hormone (PTH).

· The high-sodium diet resulted in a significant increase in mean urinary calcium loss and was characterised by large inter-individual variations, including non-responders.

· The intervention diet being rich in fruits and vegetables (an average of 8 portions per day) and therefore potassium and associated alkaline salts may have contributed to calcium conservation. Recent NDNS data for this age group shows that the average potassium intake is only about 10% lower than that investigated by the DASH trial which was found to be beneficial for bone turnover when calcium intake was high (Lin et al., 2003). Promoting a further increase in fruit and vegetable intake in this age group appears to be a less promising strategy for promoting bone health than a reduction in salt or increase in calcium intake. The interactions between various levels of calcium, protein, potassium, fruits and vegetables, and sodium in the diet and their respective effect on bone health should be further explored in free-living populations in relation to the range of 25(OH)D levels commonly observed in the UK population.

· The efficiency of calcium absorption from a standardized test meal following a 4-week adaptation period to each diet was not statistically significant between diets. However, due to the differences in daily Ca intake, there was an approx. 2-fold increase in total Ca absorbed between low and high Ca diets. The increase in calcium uptake during consumption of the high calcium diets will contribute towards improving calcium balance but the calciuric effect of sodium prevents the full utilisation of the extra calcium.

· A high calcium intake resulted in significantly reduced bone turnover. The bone resorption markers Dpy and Pyr increased during the consumption of low calcium diets (A and C) while NTx showed a significant reduction on the high calcium diets (B and D). This suggests that the response of different types of bone resorption markers will vary according to the dietary modulator. Further, there was an almost significant tendency towards increased levels of NTx in response to the high salt diets (C and D; p = 0.0595) but this trend was not seen for Dpy or Pyr. There was also a significant increase in % change from baseline for B-ALP on diets A and C (low calcium) compared to diets B and D (high calcium) suggesting an increase in bone formation activity and overall bone turnover following a reduction in calcium intake. Monitoring the effect of diet on bone turnover may therefore benefit from measuring a combination of bone resorption and formation markers.

· The bone calcium balance predicted by the compartmental analysis of calcium kinetics confirms the outcome of the bone biomarker analysis which demonstrated increased bone resorption in response to the low calcium diet. There was only a marginal (non-significant) effect of sodium on bone resorption at low calcium intake. The compartmental analysis of calcium kinetics agrees with the bone biomarker assessment in that most individuals will benefit from a high calcium intake to reduce bone loss. Deposition of calcium into bone (VO+) was not different between the diets but bone resorption (VO-) was significantly higher during the low calcium interventions (A and C; p < 0.0001). The inter-individual variation in the metabolism of calcium, coupled with the small number of subjects prevents predictions of calcium intake levels required to minimize bone calcium loss. However, our data, taken in conjunction with published data on calcium kinetics (O’Brien et al., 1995; Wastney et al., 1996) and bone biomarker studies (McKane et al., 1996; Elders et al., 1998), suggest that a calcium intake of 1200mg per day or more is likely to promote optimum calcium retention.

· The outcome of this study suggests that with vitamin D sufficiency, calcium rather than salt intake, at levels commonly consumed by this age group, determine bone calcium balance.

There is a need for further studies that consider the level of salt intake in relation to the complexity of typically consumed diets. Results obtained for postmenopausal women may not be easily extrapolated to other age groups because the importance of the effect of diet and/or other determinants of bone health may vary with age.

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