Incidence rate of type 2 diabetes is >50% lower in GrassrootsHealth cohort with median serum 25-hydroxyvitamin D of 41 ng/ml than in NHANES cohort with median of 22 ng/ml.

Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged ≥20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the GrassrootsHealth (GRH) cohort was 41 ng/ml (N=4933) while in the 2005-6 National Health and Nutrition Examination Survey (NHANES) it was 22 ng/ml (N=4078) (P<0.0001). The adjusted annual incidence rate of type 2 diabetes was 3.7 per 1000 population (95% confidence interval=1.9, 6.6) in the GRH cohort, compared to 9.3 per 1000 population (95% confidence interval=6.7, 12.6) in NHANES. In the NHANES cohort, the lowest 25(OH)D tertiles (<17, 17-24 ng/ml) had higher odds of developing diabetes than the highest tertile (OR: 4.9, P=0.02 and 4.8, P=0.01 respectively), adjusting for covariates. Differences in demographics and methods may have limited comparability. Raising serum 25(OH)D may be a useful tool for reducing risk of diabetes in the population.

Chronic dietary fiber supplementation with wheat dextrin does not inhibit calcium and magnesium absorption in premenopausal and postmenopausal women.

This placebo-controlled, randomized, crossover clinical study examined the effect of chronic wheat dextrin intake on calcium and magnesium absorption. Forty premenopausal and post menopausal women (mean ± SD age 49.9 ± 9.8 years) consumed wheat dextrin or placebo (15 g/day) for 2 weeks prior to (45)calcium ((45)Ca) and (26)magnesium ((26)Mg) absorption testing. After a standardized breakfast, serial blood and urine samples were obtained. The mean ± SD area under the curve from 0 to 9 h for (45)Ca specific activity was 0.81 ± 0.21 for wheat dextrin and 0.82 ± 0.22 for placebo, showing that wheat dextrin had no effect on calcium absorption. The mean ± SD percentage excess of (26)Mg/(24)Mg was 7.8% ± 2.1% for wheat dextrin and 7.9% ± 2.6% for placebo, showing that wheat dextrin had no effect on magnesium absorption. In conclusion, chronic wheat dextrin consumption did not inhibit calcium or magnesium absorption from the gastrointestinal tract in women.

Variability in the measured response of bone to teriparatide.

UNLABELLED: Apparent failures of bone mineral density (BMD) response to teriparatide at spine or hip occur even in a high compliance context (15% spine and 55% hip). Apparent non-responders nevertheless show good biomarker response, suggesting that apparent BMD non-response is due to measurement imprecision. Calcium intake may be an important determinant of hip response. INTRODUCTION: Individuals vary in response to bone active agents, but that variability is poorly quantified and its basis is not well understood. The study included 203 postmenopausal women with moderately severe osteoporosis, all treated with teriparatide, calcium, and vitamin D. The study was performed at the Creighton University Medical Center, a single site. METHODS: This is a prospective study of change in bone mineral density and resorption biomarkers over a 12-month treatment period. BMD response at spine and total hip was quantified by computing slopes for each participant's values, and biomarker change by the difference in values across the 12-month study period. RESULTS: Of the total number of participants, 85.2% exhibited a significant spine BMD response, while only 44.8% had a significant change at the hip. However, mean biomarker response was marginally larger for the BMD non-responders at either site than for the responders, indicating biological, if not measurable densitometric, activity of teriparatide in essentially all participants. CONCLUSIONS: Occasional apparent failures of BMD response in patients receiving teriparatide are probably not due to failure of response at the level of the bone remodeling apparatus, but instead reflect a combination of measurement imprecision and variable bone remodeling balance. The reason for the latter remains unclear.

Diagnosis and treatment of vitamin D deficiency.

The recent discovery--in a randomised, controlled trial--that daily ingestion of 1100 IU of colecalciferol (vitamin D) over a 4-year period dramatically reduced the incidence of non-skin cancers makes it difficult to overstate the potential medical, social and economic implications of treating vitamin D deficiency. Not only are such deficiencies common, probably the rule, vitamin D deficiency stands implicated in a host of diseases other than cancer. The metabolic product of vitamin D is a potent, pleiotropic, repair and maintenance, secosteroid hormone that targets > 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. A common misconception is that government agencies designed present intake recommendations to prevent or treat vitamin D deficiency. They did not. Instead, they are guidelines to prevent particular metabolic bone diseases. Official recommendations were never designed and are not effective in preventing or treating vitamin D deficiency and in no way limit the freedom of the physician--or responsibility--to do so. At this time, assessing serum 25-hydroxy-vitamin D is the only way to make the diagnosis and to assure that treatment is adequate and safe. The authors believe that treatment should be sufficient to maintain levels found in humans living naturally in a sun-rich environment, that is, > 40 ng/ml, year around. Three treatment modalities exist: sunlight, artificial ultraviolet B radiation or supplementation. All treatment modalities have their potential risks and benefits. Benefits of all treatment modalities outweigh potential risks and greatly outweigh the risk of no treatment. As a prolonged 'vitamin D winter', centred on the winter solstice, occurs at many temperate latitudes, < or = 5000 IU (125 microg) of vitamin D/day may be required in obese, aged and/or dark-skinned patients to maintain adequate levels during the winter, a dose that makes many physicians uncomfortable.

Calcium fortificants: overview and strategies for improving calcium nutriture of the U.S. population.

Despite more than 20 y of awareness of the importance of calcium to health, U.S. calcium intakes remain suboptimal. Fortification of foods with shortfall nutrients is probably the optimal strategy for dealing with widespread nutrient deficiencies, as it has the best chance of reaching the population segments most at risk, as contrasted with attempts at changing individuals' food choices or relying on voluntary supplement taking. Given the wide array of potential calcium fortificants and fortification levels, there is not much to guide manufacturers interested in improving the nutritional value of their products. In this review, we assemble the calcium salts/complexes that have been used or proposed for use as fortificants and describe certain of their measured characteristics that relate to incorporation into foods, particularly what is known of their absorbability. The calcium salts most commonly used as supplements or fortificants exhibit similar absorbability when tested in pure chemical form. Choice of salt will depend mainly upon cost, compatability with the manufacturing process, and consumer acceptability. However, interaction with food, tablet, or beverage matrices can degrade intrinsic absorbability substantially. As a consequence, each product must be explicitly tested to establish the degree to which its calcium is available to consumers.

Vitamin D inadequacy among post-menopausal women: a systematic review.

BACKGROUND: Vitamin D inadequacy has been studied extensively, due to concerns about ageing populations, associations with osteoporosis and other disorders (including non-musculoskeletal), and high prevalence. AIM: To review recent reports on the prevalence of vitamin D inadequacy among post-menopausal women with and without osteoporosis and/or other musculoskeletal diseases. DESIGN: Systematic review. METHODS: We reviewed publications in the past 10 years reporting prevalence estimates for vitamin D inadequacy, reported as serum 25(OH)D values below various levels. Thirty published studies in the English language were identified, from January 1994 through April 2004. RESULTS: In osteoporotic populations, the prevalence of 25(OH) vitamin D concentration <12 ng/ml ranged from 12.5% to 76%, while prevalence rates reached 50% to 70% of patients with a history of fracture(s) using a cut-off of 15 ng/ml. In post-menopausal women, the prevalence of 25(OH) vitamin D concentrations

Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake.

Calcium malabsorption, hypocalcemia and skeletal demineralization are well-recognized features of untreated celiac disease. This study investigates calcium absorption and bone mineral density (BMD) after a prolonged, over 4 years, treatment with a gluten-free diet. Twenty-four adult females with treated celiac disease and twenty age- and sex-matched control subjects were studied. Mean body mass index (MBI), energy intake, serum calcium, and serum 25(OH)D concentrations in treated celiacs did not differ from controls. However, while both dietary calcium and protein intake were significantly higher in celiacs (P<0.012), fractional calcium absorption was lower (mean percentage+/-SD; treated 39.8+/-12 versus controls 52.3+/-10, P<0.001). Thus, after adjusting for calcium intake, the estimated amount of calcium absorbed daily was similar in both groups. Whole body, spine and trochanter BMD were significantly lower in treated celiac patients compared with controls (P<0.05). There were significant inverse correlations between: serum parathyroid hormone (PTH) and femoral neck or total body BMD (P<0.01), PTH and duration of gluten-free diet (P=0.05), and fractional calcium absorption and alkaline phosphatase (P=0.022). Increased calcium intake could potentially compensate for the reduced fractional calcium absorption in treated adult celiac patients, but may not normalize the BMD. In addition, the inverse correlation between PTH and time following treatment is suggestive of a continuing long-term benefit of gluten withdrawal on bone metabolism in celiac patients.

Co-dependence of calcium and phosphorus for growth and bone development under conditions of varying deficiency.

The purpose of this study was to quantify the effect of variation in calcium intake, with and without supplemental phosphorus, on growth and bone development in growing animals under conditions of varying calcium and phosphorus deficiency. Nine groups of weanling male rats were fed a diet nutritionally complete, except for calcium and phosphorus, for 28 days. This diet provided nine levels of varying calcium and phosphorus repletion, using either calcium carbonate, dicalcium phosphate, or tricalcium phosphate. Body weights and diet consumption were measured throughout the test period. At term, the femurs from each animal were weighed, measured for tensile strength, bone mineral content (BMC), and bone density, and analyzed for ash, calcium, phosphorus, and histology. As expected, at equivalent levels of calcium supplementation, the two phosphorus-containing salts promoted significantly greater improvement in all the bone variables measured, as well as greater body weight gain and diet and calcium utilization, compared to animals supplemented with calcium only. Histomorphometric analysis confirmed the results of the mineral analysis and showed the structural impact of the inadequate mineral intake. The mean values for ash weight, BMC, and tensile strength in the nine diet groups were well fit (R(2) values ranging from 0.93 to 0.99) by multivariate models incorporating only the diet content values for calcium and phosphorus. In these models, the value for the phosphorus coefficient was three to sixfold larger than that for the calcium term, indicating a substantially greater effect of varying phosphorus intake than of varying calcium. These results demonstrate both the co-dependence of calcium and phosphorus in bone development and the importance of providing both minerals to support soft tissue and bone growth.

Effects of caffeine on bone and the calcium economy.

Caffeine-containing beverage consumption has been reported to be associated with reduced bone mass and increased fracture risk in some, but not most, observational studies. Human physiological studies and controlled balance studies show a clear but only a very small depressant effect of caffeine itself on intestinal calcium absorption, and no effect on total 24-h urinary calcium excretion. The epidemiologic studies showing a negative effect may be explained in part by an inverse relationship between consumption of milk and caffeine-containing beverages. Low calcium intake is clearly linked to skeletal fragility, and it is likely that a high caffeine intake is often a marker for a low calcium intake. The negative effect of caffeine on calcium absorption is small enough to be fully offset by as little as 1-2 tablespoons of milk. All of the observations implicating caffeine-containing beverages as a risk factor for osteoporosis have been made in populations consuming substantially less than optimal calcium intakes. There is no evidence that caffeine has any harmful effect on bone status or on the calcium economy in individuals who ingest the currently recommended daily allowances of calcium.

Risedronate reduces the risk of first vertebral fracture in osteoporotic women.

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score = -3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg ( n = 328) or placebo ( n = 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P = 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P = 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P = 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause.