IBMS/ECTS 2001 - PROGRAM and ABSTRACTS
SATELLITE SYMPOSIUMCALCIUM AND VITAMIN D IN OSTEOPOROSIS - SUPPLEMENTATION OR TREATMENT?
Click on the abstract number to view the symposium programTHE IMPORTANCE OF CALCIUM AND VITAMIN D TO BONE HEALTH THROUGHOUT LIFE
R. P. Heaney
Creighton University, Omaha, Nebraska, USA
Calcium is the principal cation of bone, and must be ingested in sufficient quantity both to amass the amount needed during growth and to offset daily excretory losses that would otherwise deplete previously acquired skeletal reserves. Intestinal calcium absorption efficiency is low, with gross absorption from typical diets averaging ~30%, and net absorption, ~15%. Additionally, obligatory calcium losses are generally high. Hence intake needs to be higher still to ensure absorption of enough calcium to protect bone mass. These relationships constitute the basis for the estimation of the requirement.
Because calcium can be retained only as bone, and because maximal bone mass is determined by mechanical loading and the genetic program, it is not possible to retain calcium above the quantity needed for current skeletal loading. Thus calcium is a threshold nutrient and an individual’s skeletal requirement for calcium is the intake that ensures maximal retention. During growth, that retention value will be positive; during maturity, zero; and during involution, variably negative. At below-adequate intakes, calcium retention will be less than maximal, i.e., bone mass accrual will be less than it could be during growth, bone will be lost during the mature years, and age-related bone loss, due to a combination of involutional factors, will be exaggerated.
Different racial and ethnic groups exhibit differing relationships between intake, absorption, and excretion, and hence have different intake requirements for maximal skeletal retention. While all racial groups show the same basic relationship at suboptimal intakes (i.e., higher retention at higher intakes), available evidence indicates that the retention threshold for blacks is substantially lower than for whites or orientals. Similarly, suboptimal intakes of protein, phosphorus, vitamin D, and other nutrients also affect the location of the maximal retention threshold. Vitamin D is particularly important, since at suboptimal inputs, the body adapts by increasing parathyroid secretion, and with it, bone remodeling activity.
Augmented calcium intakes – above the dietary reference values for most nations up till now – have been shown to improve calcium retention during growth, to reduce age-related bone loss, and to reduce fracture risk in the elderly (particularly hip fracture) by as much as 46%. For both calcium and vitamin D, the size of the benefit will be a function of the difference between current and optimal inputs. The fact that the effect wanes when the supplement is discontinued is what would be expected on replacing (and withdrawing) any deficient nutrient.
For optimally nourished Caucasian adolescents, the threshold intake is in the range of 1400–1600 mg (35–40 mmol)/d. After growth the threshold value drops to the range of 800–1000 mg (20–25 mmol)/d. And for the elderly, the threshold value rises to ~1600 mg (40 mmol). This latter rise is not due to growth (as at puberty), but to deteriorating ability to adapt to low intakes.
WHAT ARE THE DIETARY REQUIREMENTS FOR CALCIUM AND VITAMIN D?
A. Prentice
MRC Human Nutrition Research, Cambridge, UK
Dietary recommendations for calcium and vitamin D vary considerably between different advisory bodies. For example for elderly women, the European PRI and UK RNI for calcium are 700 mg/d, while the USA/Canada AI is 1200 mg/d, and for vitamin D are 0-10 µg/d, 10 µg/d and 15 µg/d respectively. Similar discrepancies occur in all population groups.
This lack of consensus largely reflects the different criteria used as a basis for estimating reference values. For calcium, many have used a factorial approach, where estimates of skeletal accretion rates are coupled with assumptions about calcium absorption and excretion on typical diets. Others have made use of data derived from balance studies. A recent refinement of this approach, adopted by USA/Canada in 1997, involves the mathematical modelling of balance data to estimate a calcium intake above which calcium retention is maximal. A third approach was used by a NIH Consensus Conference in 1994, based on the concept that there is a calcium intake that is optimal for bone health, in terms of reduced risk of osteoporosis in later life. Their recommended calcium intake for elderly women was 1500 mg/d. Although taken up by several special-interest groups, this approach has yet to be adopted by any committee advising on nutrition policy because of the lack of quantitative data on which to base estimates of average requirements.
Differences in vitamin D recommendations reflect subtle differences in philosophy about how to indicate that while endogenous synthesis is the main source of vitamin D for people with adequate sunlight exposure, there are vulnerable groups that rely on the diet to supply their vitamin D requirements. In addition, they reflect uncertainties in the relationship between vitamin D status and health outcomes.
CALCIUM AND VITAMIN D IN OSTEOPOROSIS - SUPPLEMENTATION OR TREATMENT?
P. Burckhardt
University Hospital, Lausanne, Switzerland
Vitamin D as supplement: Vitamin D and its metabolites were first used in declared deficiencies (rickets, osteomalacia, renal osteopathy). Later, subclinical hypovitaminosis, defined by elevated PTH, became a new indication; first in institutionalized elderlies, then in healthy, free living, elderly and even middle aged persons. Indeed, vit.D decreased bone loss in elderlies, increased BMD, improved ultrasonic bone data, and lowered hip fracture incidence in elderlies (with Ca). This illustrates the contribution of latent vit.D deficiency to the pathogenesis of OP, and justifies the use of vit.D in OP, esp.of the elderlies, as a supplement.
Calcium as supplement: low Ca intake negativates Ca balance and accelerates bone loss in the postmenopause and in elderlies. Insufficient intake is frequent. Therefore, Ca supplementation is recommended, esp. in OP; it decreases bone loss, even with some antifracture effect.
Calcium as antiresorptive drug: Although less effective than drugs, 1g Ca lowers PTH and bo-ne resorption immediately, decreased the latter in the longterm by about 20%, and increased BMD slightly, thanks to the mineralization of resorption spaces. This was obtained with 1-3g above nutritional intake, more than used as supplements. Because Ca was rarely compared to placebo, its effectiveness as drug is underestimated. Vit. D is believed to be more effective, for stimulating bone mineralisation, and less for enhancing Ca absorption, which lowers PTH secretion, because for that it could be replaced by high Ca supplements. If vit.D given alone is less effective than when given with Ca, is unknown. But its addition enhances the effect of Ca.
Vitamin D and its metabolites as drugs: In the absence of documented vit.D deficiency, their use is advocated because of: decline of the dermal production of vit.D with age, lack of vit.D 1a-hydroxylase due to lack of estrogen, or to age-dependant lowering of responsiveness to PTH, resistance to 1.25 (OH)2 vit.D, and low UV exposure when nutritional vit.D or Ca intake is low. Only the latter is relevant, which explains why the superiority of vit.D metabolites is unproven: they could not prevent postmenopausal OP, and in the treatment of OP, a-calcidiol was positive on BMD mainly in Japan, where Ca intake is low, and latent vit.D deficiency probable, with no unbiased antifracture effect. One study with calcitriol points to a beneficial antifracture effect. Controlled trials with calcitriol showed more effect on fractures than trials with a-calcidiol, but hyper-calciuria and -calcemia became rel.frequent. Perhaps beneficial effects could only be expected in vit.D deficient patients, but the plasma levels were measured in only 1 study. The antifracture effect of Calcitriol in 1 study remains unconfirmed; the same results could eventually have been obtained with a-calcidiol or with vit.D.
The use of vit.D as a drug also has extraosseaous targets. Body sway and quadriceps strenght were recognized as predictive factors of nonvertebral fractures. Although not definitely linked to vit.D deficiency. Vit.D (eventually also calcitriol), given with Ca, stimulates muscle strength and decreased body sway and the number of falls. If this is a therapeutic effect or that of the correction of a state of deficiency, is unknown.
THE TIMING, DOSE AND CHOICE OF CALCIUM AND VITAMIN D
J. Y. Reginster*, B. Zegels, R. Deroisy, E. Lejeune, A. N. Taquet
WHO Collaborating Center for Public Health Aspects of Rheumatic Disorders, Liège, Belgium
Bone and Cartilage Research Unit, University of Liège, Belgium
The role of secondary hyperparathyroidism in the pathogenesis of osteoporotic fractures, in the elderly is no longer disputed. Taking into account the demonstration of a significant reduction in hip and all non vertebral fractures when elderly subjects are supplemented with calcium-vitamin D preparations, it seems necessary to recommend calcium-vitamin D supplementation to be given to elderly. An important issue is constituted by the optimal regimen of calcium-vitamin D supplementation in order to provide a maximal sideration of parathyroid hormone secretion, hence protecting the skeleton against increase in bone resorption and turnover.
We reported here the main results of some investigations which have attempted at the identification of the best daily dose and sequence of administration of calcium and vitamin D inducing an optimal parathyroid hormone decrease.
The influence of calcium load on absorption fraction has been previously reported: it varies inversely with intake and a divided dose regimen results in substantially greater absorption of calcium than a one daily dose supplementation.
Furthermore, a comparison of body retention of calcium, measured using a radionuclide method after acute oral administration of 1000 mg elemental calcium in one or two doses, has shown that calcium retention was significantly better with two daily doses of 500 mg than with a single 1000 mg dose.
Moreover, comparing the bioavailability of five different calcium preparations, we reported significant differences in suppression of parathormone between them suggesting that the choice of the calcium salts is an important parameter.
Recently, we demonstrated that the administration of two times 500 mg of calcium and 400 IU of vitamin D3, at six-hour intervals provides a more prolonged decrease in serum parathyroid hormone levels than the administration of the same total amount of calcium and vitamin D, as a single morning intake in young healthy volunteers.
Thus, daily dose and timing administration of calcium and vitamin D supplements, but also calcium salts choose, seems to modify decrease in serum parathyroid hormone levels.
This might have implications in terms of protection of the skeleton against secondary hyperparathyroidism and increased bone resorption and turnover, in elderly subjects.
