Robert Heaney

..What is important to note is that, in the case of vitamin D, the preponderance of the evidence indicates that there is real, preventable disease in the range of vitamin D status values now labeled "insufficient."..

..Several alternative approaches, each providing an a priori normal, are described and briefly discussed...

..Nutritionists and dietetics professionals should encourage manufacturers of fortified products to provide information on bioavailability...

..Problems with adherence to a regimen of taking supplements daily make an appropriate fortification strategy the preferred option for improving the status of both nutrients...

..The best source of calcium is dairy foods, largely because the disorders concerned depend upon multiple nutrients, not just calcium, and dairy provides a broad array of essential nutrients in addition to calcium, and at low cost...

..Given the relative difficulty of the former, and the ancillary benefits of the latter, it would seem that the optimal strategy to protect the skeleton is to ensure adequate calcium and potassium intakes...

..The age-related decline in cutaneous input, taken together with the UL, creates a substantial barrier to the deployment of public health strategies to optimize vitamin D status in the elderly...

..Higher calcium intakes not only support the skeleton in African Americans, just as they do in whites, but reduce the disease burden for other chronic diseases as well...

..There is great need for standardization and improved reproducibility and sensitivity of measurements of serum 25(OH)D3 concentrations...

..Intercurrent illness resulting in hospitalization produced a rapid bone loss across the period of illness comparable in magnitude to documented age-related loss. Risedronate in a dose of 5 mg/day effectively abolished this loss...

..Actual toxicity is not seen below serum 25OHD values of 250nmol/L, a value that would be produced only at continuing oral intakes in excess of 10,000IU (250microg)/day...

..Its efficacy in reducing fracture risk is expected to be at least as good as that of once-weekly alendronate given for the same indications...

....

..High calcium intakes in postmenopausal and older women reduce this homeostatic remodeling to approximately pre-menopausal values and improve bone strength immediately, well prior to any appreciable change in bone mass...

..Hence a strong case can be made for immediate improvement in vitamin D status of the general population...

..Recent data indicate that cholecalciferol (vitamin D(3)) is substantially more potent than ergocalciferol (vitamin D(2)) and that the safe upper intake level for vitamin D(3) is 10,000 IU/d...

..To characterize methods evaluating and to summarize studies linking various serum 25-hydroxyvitamin D [25(OH)D] concentrations with health status...

..Moreover, by failing to use a physiological referent, the IOM approach constitutes precisely the wrong model for development of nutritional policy...

..Current unitage for the calciferols suggests that equimolar quantities of vitamins D(2) (D2) and D(3) (D3) are biologically equivalent. Published studies yield mixed results...

..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...

..The relative effectiveness of various calcium salts for this purpose is uncertain. Many older women with osteoporosis have phosphorus intakes of <70% of the Recommended Dietary Allowance...

..To estimate the amount, type, and tissue distribution of vitamin D in the adult body under typical inputs...

..Given modern food sources, it is difficult to devise a diet that is "bone healthy" without including three servings of dairy per day, not just because of dairy calcium, but dairy protein and potassium as well...

..In this review, one way of doing so is proposed and the recently emergent literature concerning calcium intake and body composition is used as an illustration of how such an approach might be used...

..A report of a small increase in kidney stone risk in the calcium treatment arm of the Women's Health Initiative (WHI) led to a reduction in U.S. calcium supplement sales...

..Toxicity is associated only with excessive supplemental intake (usually well above 20,000 IU/day)...

..To a considerable extent, both vitamin D status and the benefits associated therewith appear to be dependent on, or at least augmented by, calcium intakes at or above currently recommended levels...

..Neither the efficiency of the 25-hydroxylation of vitamin D nor the steady state relation between vitamin D(3) and 25-hydroxyvitamin D [25(OH)D] has been studied in humans...

..The partition described facilitated derivation of a formula to calculate TIC for any paired values of EFC and AbsFx, i.e. TIC = EFC/[0.223 + 0.777 (1 - AbsFx)]...

..A calcium phosphate supplement may be preferable to the usual carbonate or citrate salts because its phosphate serves to spare food phosphorus...

....

..The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known, particularly within ranges comparable to the probable physiologic supply of the vitamin...

..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...

..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...

..Milk, mainly because of constructive interactions among its several key nutrients, is probably the most nutritionally and cost effective way of meeting the calcium requirement in the elderly...

..To evaluate the effect of calcium intake on absorption of dietary phosphorus, with special reference to typical calcium intakes and to those likely to be encountered in prevention and treatment of osteoporosis...

..5-3.0 kg lower body weight in adults. Taken together these data suggest that increasing calcium intake by the equivalent of two dairy servings per day could reduce the risk of overweight substantially, perhaps by as much as 70 percent...

..Phosphorus intake, less extensively studied, may be more important than currently recognized, particularly in elderly individuals living alone, eating little meat, and receiving anti-osteoporosis treatment agents...

..Intake of carbonated beverages has been associated with increased fracture risk in observational studies. The usual explanation given is that one or more of the beverage constituents increase urinary calcium...

..Published cost-benefit analyses assume equal bioavailability for all calcium sources. Some published studies have suggested that there are differences in both the bioavailability and cost of the major calcium supplements...

..Hence direct measurement of absorbability is essential to assure regulators and the general public that the source delivers what it promises...

..Several investigators have suggested that the relatively high phosphorus and protein intakes of the diets of industrialized nations reduce calcium absorption and thereby aggravate the problem of calcium deficiency...

..Additionally, the validity of isotopic labeling methods for fortified liquid products had not been established...

....

..Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency, but the vitamin D status that fully normalizes absorption is not known for humans...

..Prudent nutritional support for osteoporosis prevention and treatment consists of 30 to 40 mmol Ca/d together with sufficient vitamin D to maintain serum 25(OH)D levels above 80 nmol/L (i.e., approximately 25 microg vitamin D/d)...

....

..For net absorbed calcium (mmol) the relationship was given by 4.358 x AUC(9) +/- 0.820. The empirical regression coefficient was significant and the error of the estimate (0.820 mmol) acceptably small...

..Within this context, reduced bone mass, rather than the primary cause of fracture, is seen as a factor that predisposes individuals to the harmful effects of excessive remodeling...

..One consequence is that if BMC-based T-scores are used to classify patients, substantially fewer individuals would have been judged osteoporotic in this cohort (two-thirds fewer for spine and three-fourths fewer for hip)...

..At the hip, 98.0% of BMD variation is due to BMC and 1.1% due to bone areal size. The current study may be important in understanding the relationship among BMD, BMC, and bone size as risk determinants of osteoporotic fractures...

..CONCLUSION: As a first approximation, the amount of endogenous calcium entering the digestive stream rises with body size and with the amount of phosphorus-rich food consumed...

..There is much interest in dosing vitamin D intermittently for patient convenience and long-term adherence...

..Our study is the largest longitudinal study reported to date and provides, perhaps, a more secure basis for estimating muscle mass change with age than has been available heretofore...

..QUS predicted stress fracture in female recruits as well as it predicts hip fracture in elderly women. Recruits with low QUS values and a history of smoking and not exercising had an extremely high risk of stress fracture...

..Dietary potassium intake (K) lowers urinary calcium (Ca) excretion and, in short-term studies, may improve Ca balance...

..We found that DHA-induced melanoidins in skin act as a topical sunscreen attenuating the formation of 25(OH)D...

..Inadequate vitamin D nutritional status is increasingly recognized as common in North American and European populations, but the extent of the shortfall and the parameters of the distribution for populations of interest remain uncertain...

..This study compared intestinal Ca absorption in hemodialysis patients treated with calcitriol versus paricalcitol (dose ratio 1:3)...

..5:1.Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3)...

..The issue for public health professionals is whether recommended protein intakes should be increased, given the prevalence of osteoporosis and sarcopenia...

..Vitamin D(3) inputs from all sources required to sustain such a level amount to 3600-4200 IU/d. Daily oral intakes as high as 10,000 IU are safe...

....

..Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking...

..Despite this input, at the late winter visit, 25(OH)D was less than 50 nmol/liter in 3 subjects and less than 75 nmol/liter in 15 subjects...

..Calcium intake in North America remains substantially below recommended amounts. Bottled waters high in calcium could help close that gap...

....

..Ultraviolet (UV)-B light increases vitamin D levels, but the dose response and the effect of skin pigmentation have not been well characterized...

..Moreover, bone resorption responds rapidly and sensitively to improvements in calcium intake that are readily achievable by an older female population...

..Mean 24-h urinary potassium averaged 92% of dietary intake. According to nationwide food consumption surveys, milk is the number 1 single food source of potassium in all age groups in the United States...

..48 (0.09), 0.64 (0.08), and 0.60 (0.09) for bone size at the hip, spine, and wrist...

..Ac.f nearly doubled 1 year after menopause, tripled 13 years after menopause, and remained elevated in women with osteoporosis...

..CONCLUSION: The magnitude of the effect is such that a woman 1.8 m in height would absorb 30+% more calcium from a given intake than a woman 1.4 m tall...

..Few community-based studies allow estimation of the dose-response relationship between oral intake of vitamin D and corresponding serum 25(OH)D in the range above 1,000 IU/d...

..We suggest a full scientific review of cereal-grain enrichment with calcium and vitamin D...

..Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture...

..0675 +/- 0.016). Calcium sulfate is a bioavailable fortificant for white bread that compares favorably with milk and two other salts...

..This paper describes the dilemmas faced by the DSMB and the considerations it made over the course of its existence. The paper concludes with some recommendations for other DSMBs...

....

..abstract_text> ..