Bone health

Bone health1–3 Robert P Heaney ABSTRACT Much evidence indicates that both calcium and vitamin D are efficacious in protecting the skeleton, particularly when these 2 nutrients are used in combination. Each nutrient is necessary for the full expression of the effect of the other, and where their actions are independent, their effects on skeletal health are complementary. Nutrient status for both tends to be deficient in the adult population of the industrialized nations. Hence, supplementation or food fortification with both nutrients is appropriate and, given contemporary diets and sun exposure, probably necessary. Various meta-analyses, systematic evidence reviews, and controlled trials evaluating these 2 nutrients will be defective if they fail 1) to take into consideration the nearly universal need to augment the status of both nutrients in the populations studied rather than just one or the other, 2) to consider the threshold characteristics of both nutrients, and 3) to use the achieved serum 25-hydroxyvitamin D concentration as the independent variable for vitamin D effects (instead of oral vitamin D intake). 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. Am J Clin Nutr 2007; 85(suppl):300S–3S. KEY WORDS Calcium, vitamin D, fractures, falls, bone health, supplementation, fortification fails to get the recommended intake of calcium, and, depending on the age and population group studied, from 65% to nearly 100% of the population after mid-life has a serum 25hydroxyvitamin D concentration [25(OH)D] 쏝80 nmol/L (which many lines of evidence suggest may be the lower limit of the healthy range). Hence, consideration of nutritional supplementation is appropriate, not only at an individual level, but also at a population level. The Surgeon General, in his Report on Bone Health and Osteoporosis (9) stated “Calcium has been singled out as a major public health concern today because it is critically important to bone health and the average American consumes levels of calcium that are far below the amount recommended for optimal bone health.” Because calcium and vitamin D, administered together, have been shown to reduce fracture risk in randomized controlled trials and because those studies have been incorporated into existing policy statements (4 –9), I will not present that evidence again here. It may be more useful to look at the mechanisms by which the 2 nutrients produce their beneficial effects. Understanding these mechanisms may provide useful insights on how both to enhance and to evaluate efficacy. With reference to skeletal health specifically, both calcium and vitamin D act in 2 distinct ways: by offsetting obligatory calcium losses from the body and by reducing excessive bone remodeling. INTRODUCTION Of the nutrients generally included under the heading multivitamins and minerals, the 2 most directly related to bone health are calcium and vitamin D. In evaluating evidence relating to their efficacy, it is important that they be considered together. This is because each needs the other for certain of its actions and, where they function independently, each complements the other with respect to various bone health endpoints. Meta-analyses or other systematic evidence reviews that analyze studies of the 2 nutrients separately, and especially those that exclude studies testing the combination, are likely to produce misleading conclusions (1–3). CALCIUM AND VITAMIN D—A PARTNERSHIP A large body of evidence, reviewed extensively elsewhere (4 –10), indicates that supplementing calcium and vitamin D has positive effects on both health. Specifically, these nutrients enhance bone gain during growth, reduce age-related bone loss, and reduce fragility fractures, particularly in the elderly and probably in adolescents as well. Such outcomes are plausible in view of the fact that roughly 85% of the female population after childhood 300S OFFSETTING OBLIGATORY LOSSES The initial conceptual framework relating calcium and vitamin D to bone health centered on the fact that obligatory losses of calcium from the adult human body are relatively high and calcium absorption efficiency is relatively low. This creates a need both to have a high calcium intake and to absorb it with reasonable efficiency. To protect extracellular fluid [Ca2ѿ] when absorbed calcium is not sufficient to offset obligatory losses, bone will be torn down to scavenge its calcium. In this arrangement, a high calcium intake is important because it is the bulk input needed to offset corresponding outputs. Vitamin D is important because it is necessary for efficient absorption of calcium from the diet. This conceptual framework remains essentially 1 From Creighton University, Omaha, NE. Presented at the conference “Multivitamin/Mineral Supplements and Chronic Disease Prevention,” held at the National Institutes of Health, Bethesda, MD, May 15–17, 2006. 3 Reprints not available Address correspondence to RP Heaney, Creighton University Medical Center, 601 North 30th Street, Suite 4841, Omaha, NE 68131. E-mail: . 2 Am J Clin Nutr 2007;85(suppl):300S–3S. Printed in USA. © 2007 American Society for Nutrition BONE HEALTH 301S FIGURE 1. Plots of the cumulative incidence of fractures, redrawn from the studies of Chapuy et al (17) (right) and Dawson-Hughes et al (18) (left). In both cases, the upper line represents the placebo control subjects and the lower line represents the subjects treated with calcium and vitamin D. The shaded zones represent the reduction of fracture risk, which, as can be readily seen, starts with the beginning of treatment. (Copyright Robert P Heaney, 2004. Used with permission.) correct today, although in its initial form it tended to be qualitative, rather than quantitative. For example, although the need for vitamin D to promote active intestinal calcium absorption was recognized, the amount of vitamin D needed was not known. REDUCING EXCESSIVE BONE REMODELING The second mechanism of action has become apparent only very recently. Both calcium and vitamin D, particularly together, reduce excessive bone remodeling. Bone remodeling doubles across menopause and triples by the age of 65 y (11). Originally, remodeling had been envisioned primarily as a repair mechanism, replacing damaged bone with fresh new bone. Hence, remodeling was seen as osteoprotective. Although that function still remains important, the rise in remodeling after midlife appears to be driven by hormonal changes and nutritional factors rather than by the need to repair bone. Several lines of evidence show that high remodeling rates increase bone fragility (12–16) and that the reduction in fragility that follows antiresorptive therapy is probably due more to the effect of the therapy on remodeling than to its effect on bone mass (13, 14). Moreover, remodeling suppression begins immediately on i (...truncated)