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Biomedical subjects

R P Heaney

Publications and source records attributed to R P Heaney.

At least 19 recordsLinked to original sources

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 <or=20 ng/ml ranged from 1.6% to 86% for community-living and institutionalized women, respectively. The most common factors associated with inadequate vitamin D levels included limited sun exposure, lack of dietary vitamin D intake, nursing home environment, wintertime, and increasing age (over 70 years). DISCUSSION: The prevalence of inadequate vitamin D levels appears to be high in post-menopausal women, especially in those with osteoporosis and history of fracture. Vitamin D supplementation in this group might offer scope for prevention of falls and fracture, especially in elderly and osteoporotic populations.

Aged↗

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.

Absorption↗

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.

Animals↗

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.

Aged↗

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.

Animals↗

Hormones, weight change and menopause.

OBJECTIVE: To determine total body weight change occurring in women at mid-life, specifically with respect to occurrence of menopause and use of estrogen. DESIGN: Retrospective analysis of body weight measurements accumulated in two cohorts of healthy women participating in studies of skeletal metabolism. SUBJECTS: Cohort 1: 191 healthy nuns enrolled in a prospective study of osteoporosis risk, aged 35-45 in 1967; cohort 2: 75 women aged 46 or older and still menstruating, enrolled in 1988 in a study of bone cell dynamics across menopause. Roughly one-third of each group received hormone replacement after menopause. MEASUREMENTS: Body weight and height, age, menstrual status and use of estrogen replacement. Cohort 1: 608 measurements at 5 y intervals spanning a period from 17 y before to 22 y after menopause; cohort 2: 1180 measurements at 6-month intervals spanning a period from 5 y prior to 5 y after menopause. RESULTS: In cohort 1 weight rose as a linear function of age (both chronological and menopausal), both before and after cessation of ovarian function, at a rate of approximately 0.43% y(-1). Neither the menopausal transition nor the use of estrogen had an appreciable effect on this rate of gain. In cohort 2 the rate of gain seemed to diminish slightly at menopause. As with cohort 1, hormone replacement (or its absence) had no appreciable effect on weight. CONCLUSIONS: The long-term, total body weight trajectory at mid-life is not influenced appreciably by either cessation of ovarian function or by hormone replacement.

Adult↗

Calcium needs of the elderly to reduce fracture risk.

Contemporary calcium intakes in the industrialized nations are substantially lower than those to which human physiology is adapted by evolution. As a result, compensatory adjustment is required lifelong. This adjustment consists of high levels of parathyroid activity, leading to parathyroid hyperplasia, high circulating levels of 1,25(OH)2D and high bone turnover. The capacity of these compensatory mechanisms to provide sufficient calcium to offset daily losses from the body declines with age; hence, increasingly the body tears down bone to access its calcium. As a result, the calcium requirement for skeletal maintenance is said to rise with age. Supplemented intakes to a total in the range of 32.5-42.5 mmol (1300-1700 mg)/day have been shown to arrest age-related bone loss and to reduce fracture risk in individuals 65 and older and intakes of 60 mmol (2400 mg), to restore the setting of the parathyroid glands to young adult values. Intakes at such levels also minimize the expression of other disorders such as colon cancer, hypertension and obesity, all of which, while multifactorial, have a calcium deficiency component. 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.

Aged↗

Absorbability and cost effectiveness in calcium supplementation.

BACKGROUND: Cost-effectiveness of calcium supplementation depends not only on the cost of the product but on the efficiency of its absorption. 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. DESIGN: Randomized four period, three-way cross-over comparing single doses of off-the-shelf commercial calcium supplements containing either calcium carbonate or calcium citrate compared with a no-load blank and with encapsulated calcium carbonate devoid of other ingredients; subjects rendered fully vitamin D-replete with 10 microg/day 25(OH)D by mouth, starting one week prior to the first test. SUBJECTS: 24 postmenopausal women METHODS: Pharmacokinetic analysis of the increment in serum total and ionized calcium and the decrement in serum iPTH induced by an oral calcium load, based upon multiple blood samples over a 24-hour period; measurement of the rise in urine calcium excretion. Data analyzed by repeated measures ANOVA. Cost calculations based on average retail prices of marketed products used in this study from April through October, 2000. RESULTS: All three calcium sources (marketed calcium carbonate, encapsulated calcium carbonate and marketed calcium citrate) produced identical 24-hour time courses for the increment in total serum calcium. Thus, these were equally absorbed and had equivalent bioavailability. Urine calcium rose slightly more with the citrate than with the carbonate preparations. but the difference was not significant. Serum iPTH showed the expected depression accompanying the rise in serum calcium, and there were no significant differences between products. CONCLUSION: Given the equivalent bioavailability of the two marketed products, the cost benefit analysis favors the less expensive carbonate product.

Area Under Curve↗

Constructive interactions among nutrients and bone-active pharmacologic agents with principal emphasis on calcium, phosphorus, vitamin D and protein.

Current and emerging bone active pharmacologic agents are capable of producing substantial gains in bone mass. However, nutrition must be adequate if this potential is to be realized. Calcium and vitamin D supplementation, for example, have both been demonstrated to augment substantially the skeletal response to estrogen therapy in postmenopausal women. The bisphosphonates and selective estrogen receptor modulator (SERMs) have all been tested only in the context of supplemental calcium and vitamin D. Therefore, it cannot be assumed that these bone active agents would be effective in the absence of these nutrients. Adequate protein intake has also been demonstrated to protect bone mass in the elderly and to improve recovery from osteoporotic fractures. 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.

Adaptation, Physiological↗

Carbonated beverages and urinary calcium excretion.

BACKGROUND: 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. OBJECTIVE: We assessed the short-term effects on urinary calcium excretion of carbonated beverages of various compositions. DESIGN: An incomplete random block design was used to study 20-40-y-old women who customarily consumed > or =680 mL carbonated beverages daily. Four carbonated beverages were tested: 2 with caffeine and 2 without. Two contained phosphoric acid as the acidulant and 2 contained citric acid. The study included one neutral control (water) and one positive control (skim or chocolate milk). Serving size was 567 mL for the carbonated beverages and water and 340 mL for the milks. Beverages were consumed with a light breakfast after an overnight fast; no other foods were ingested until urine collection was complete. pH, titratable and total acidity, sodium, creatinine, and calcium were measured in 2-h (morning) fasting and 5-h postbeverage urine specimens. RESULTS: Relative to water, urinary calcium rose significantly only with the milks and the 2 caffeine-containing beverages. The excess calciuria was approximately 0.25 mmol, about the same as previously reported for caffeine alone. Phosphoric acid without caffeine produced no excess calciuria; nor did it augment the calciuria of caffeine. CONCLUSIONS: The excess calciuria associated with consumption of carbonated beverages is confined to caffeinated beverages. Acidulant type has no acute effect. Because the caffeine effect is known to be compensated for by reduced calciuria later in the day, we conclude that the net effect of carbonated beverage constituents on calcium economy is negligible. The skeletal effects of carbonated beverage consumption are likely due primarily to milk displacement.

Adult↗

Factors influencing the measurement of bioavailability, taking calcium as a model.

For non-metabolizable supplemental nutrients, bioavailability is effectively equivalent to absorbability. Methods for measuring absorbability (balance, pharmacokinetic, tracer, urine increment, evoked physiological responses, and in vitro) are briefly characterized and their utility compared. When intrinsic labeling of a source is possible, tracer methods are generally the most accurate and precise, as well as often the least expensive. Factors influencing the measured end points of the various methods are described briefly. These include source factors such as pharmaceutic formulation, subject factors such as mucosal mass and the need status of the absorbing subject, and co-ingested factors such as other foods or food constituents. Extensive experience has shown that absorbability is difficult to predict from knowledge of the chemistry of the source, or even from the results of in vitro testing. Hence direct measurement of absorbability is essential to assure regulators and the general public that the source delivers what it promises.

Biological Availability↗

The bone remodeling transient: interpreting interventions involving bone-related nutrients.

The bone remodeling transient is a temporary alteration in the balance between bone formation and bone resorption, brought about by any agency that affects bone remodeling. Ascertaining the steady state effect of an intervention requires factoring the component of the change due to the transient out of the total bony response. Since parathyroid hormone (PTH) is the principal regulator of the quantity of remodeling activity, and since calcium intake influences PTH secretion, it follows that altering calcium intake will always induce a remodeling transient. Worked examples from three published calcium intervention studies are presented, and the errors that can be made by ignoring the transient and simply measuring change in bone mass across treatment are described.

Bone Development↗