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Calcium Needs of the Elderly to Reduce Fracture Risk

Creighton University, Osteoporosis Research Center, Omaha, Nebraska

Address reprint requests to: Robert P. Heaney, MD, FACN, Creighton University, Osteoporosis Research Center, 601 N. 30^th St.—Suite 4841, Omaha, NE 68131. E-mail: rheaney{at}creighton.edu.

	ABSTRACT

TOP ABSTRACT INTRODUCTION PHYSIOLOGICAL BASIS OF THE... BONE MASS, BONE STRENGTH... BONE STRENGTH AND CALCIUM... WHY THE REQUIREMENT APPEARS... NUTRIENT DEFICIENCY VS. CHRONIC... SYNTHESIS AND RECOMMENDATIONS REFERENCES

 
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.

Key words: osteoporosis, bone mineral density, parathyroid homorne

Key teaching points:

• Contemporary calcium intakes are lower than those prevailing when human physiology evolved, and they require lifelong adaptation to sustain normal blood calcium levels.

• Ability to adapt to low calcium intakes, like pulmonary, cardiovascular and other system reserves, declines with age.

• Calcium intakes of 32.5–42.5 mmol (1300–1600 mg) per day minimize age-related bone loss and reduce fracture risk in the elderly, and an intake of 60 mmol (2400 mg) returns parathyroid cell mass and blood iPTH levels to young adult values.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PHYSIOLOGICAL BASIS OF THE... BONE MASS, BONE STRENGTH... BONE STRENGTH AND CALCIUM... WHY THE REQUIREMENT APPEARS... NUTRIENT DEFICIENCY VS. CHRONIC... SYNTHESIS AND RECOMMENDATIONS REFERENCES

 
The notion that the nutrient requirements of the elderly might be different from those of other adults is a new development in the field of nutrition. As recently as the 1989 RDAs [1], the recommended values for those over age 50 were no higher than for younger adults and, for a few nutrients, actually lower. In the case of calcium, there has been a growing body of evidence to the effect that one recommendation may not fit all adults. In 1982, a special ASCN/NIA panel on nutrient requirements in the elderly [2] evaluated the evidence available and found no studies that could support a calcium requirement as low as the then current RDA, 20 mmol (800 mg)/day. This finding was reflected in the recommendations of the 1984 Consensus Development Conference on Osteoporosis [3], in which it was proposed that mature adults ingest 25 mmol (1000 mg) Ca/day and older adults, 37.5 mmol (1500 mg) Ca/day. The 1994 NIH Consensus Development Conference on Optimal Calcium Intake came to the same numerical recommendation [4], and the 1997 DRIs from the Food and Nutrition Board (IOM) also contained a recommendation for a higher intake level in the elderly than in younger adults [5]. The evidence used by the various consensus panels and the Food and Nutrition Board is extensively documented in their respective publications, as well as in more recent reviews [6]. In this presentation, therefore, I shall focus mainly on the reasons for the rise in the requirement, its implications and the change in perspective inherent in the recent revisions of the requirements.

	PHYSIOLOGICAL BASIS OF THE REQUIREMENT

TOP ABSTRACT INTRODUCTION PHYSIOLOGICAL BASIS OF THE... BONE MASS, BONE STRENGTH... BONE STRENGTH AND CALCIUM... WHY THE REQUIREMENT APPEARS... NUTRIENT DEFICIENCY VS. CHRONIC... SYNTHESIS AND RECOMMENDATIONS REFERENCES

 
Central to an understanding of the calcium requirement is the realization that, in addition to its obvious structural role, the skeleton serves as the nutrient reserve for calcium. As such, it is designed by evolution to be drawn upon in times of reduced intake or excessive loss, with the withdrawals then replaced during times of adequate intake. However, calcium is not merely stored in bone, but as bony tissue. There is only as much calcium in the skeleton as there is bony tissue itself. Unlike most other nutrients, the size of the reserve is controlled, at its upper bound, not by intake but by the mechanical function of the skeleton. The body maintains only as much bone as it needs to support current mechanical loads.

What this behavior amounts to is that calcium functions as a threshold nutrient [7–9]. For example, during growth, calcium retention by the body is a linear function of intake up to some point when the growth and mechanical needs of the skeleton have been met, above which no further calcium is accumulated, no matter how high the intake. The same basic relationship obtains during maturity and involution and is illustrated in Fig. 1A, which presents schematic retention curves for all three life stages. As the diagram indicates, when intake is adequate, retention is positive during growth, zero during maturity and perhaps negative during involution. The requirement for an individual is the point at which retention becomes maximal, i.e., above which no further increase in intake produces further retention, indicated by the asterisks in the figure. On the ascending limb of all three curves, absorbed intake is not adequate to offset obligatory losses or to meet the needs of growth, and retention is suboptimal or even negative.

View larger version (11K): [in this window] [in a new window]   Fig. 1. (A) Schematic intake and retention curves for calcium for three life stages. Retention is greater than zero during growth, zero at maturity, and may be negative during involution. (B) The involution curve only. Point B designates an intake below the maximal calcium retention threshold, and point A, an intake above the threshold. Copyright Robert P. Heaney, 1998. Reproduced with permission.

Panel B in Fig. 1 singles out the retention line for a typical elderly population and shows two points, one where the retention curve becomes flat (A), indicating the requirement, and one on the ascending limb of the curve (B), indicating the position where, from available evidence, most elderly members of the U.S. population find themselves today. It is important to recognize—and the figure attempts to make this point—that the goal of optimal calcium nutrition in the elderly is not to reverse all age-related bone loss (which is not always possible by nutritional means), but to prevent aggravation of such loss by insufficient calcium intake.

	BONE MASS, BONE STRENGTH AND RISK OF FRACTURE

TOP ABSTRACT INTRODUCTION PHYSIOLOGICAL BASIS OF THE... BONE MASS, BONE STRENGTH... BONE STRENGTH AND CALCIUM... WHY THE REQUIREMENT APPEARS... NUTRIENT DEFICIENCY VS. CHRONIC... SYNTHESIS AND RECOMMENDATIONS REFERENCES

 
Any decrease in the size of the calcium reserve means a decrease in bone mass and a corresponding decrease in bone strength. However, reduced bone mass has many causes, of which calcium deficiency is only one. And bony fragility, in turn, has many causes, of which low bone mass is but one. Other fragility factors include microarchitectural deterioration of the bony tissue and qualitative reduction in the strength of the bony material itself [10]. Osteoporotic fractures occur for all three reasons. In addition to bony fragility, the elderly individual often has a kind of total body fragility that predisposes to skeletal fractures because of an increased propensity to fall, bad postural reflexes and falling in ways that produce unusual stresses on vulnerable bony areas (e.g., the hip). Additionally, loss of soft tissue mass over bony prominences exposes them to higher point loads at the time of impact when falls do occur.

While optimal nutrition can mitigate the damage from several of these causes, the role of calcium is primarily in the maintenance of bone mass; thus, the amount of fracture reduction which is achievable with an optimal calcium intake is determined by the amount of bone loss which would otherwise be due to insufficient intake.

	BONE STRENGTH AND CALCIUM INTAKE

TOP ABSTRACT INTRODUCTION PHYSIOLOGICAL BASIS OF THE... BONE MASS, BONE STRENGTH... BONE STRENGTH AND CALCIUM... WHY THE REQUIREMENT APPEARS... NUTRIENT DEFICIENCY VS. CHRONIC... SYNTHESIS AND RECOMMENDATIONS REFERENCES

 
Despite the multiplicity of fragility factors, there is general recognition that bone mass is of considerable importance in maintaining bone strength. Other things being equal, every 12% to 15% loss of skeletal mass produces a doubling in fracture risk. Moreover, despite the fact that calcium intake is only one of the factors contributing to bone strength and fragility, available data indicate that its influence is appreciable [4–6]. Matkovic et al. [11] had noted over 20 years ago that higher calcium intakes were associated with 60% fewer fractures of the upper femur in a rural Croatian district with a high calcium intake (as contrasted with another rural district with a low calcium intake), and Holbrook et al. [12] made a similar observation for North American adults in a southern California retirement community. But these studies (and others like them) were observational in character, and it is not possible to establish a causal relationship between the associated variables with this investigative design. More recently, however, many randomized, controlled trials have been performed, and the causal connection between augmented calcium intake and fracture reduction is now firmly established.

Over 40 investigator-controlled trials of calcium supplementation have been published showing a significant bone benefit. In the elderly that benefit consisted of reduction of age-related bone loss and lessened risk of fracture. Chapuy et al. [13] produced a 30% reduction in hip and other extremity fractures within 18 months of starting elderly French women on calcium and vitamin D supplementation, and Dawson-Hughes et al. [14] found an even larger reduction in fracture risk in healthy men and women in the Boston area. Recker et al. [15] and Chevalley et al. [16] also found reduced fracture risk in individuals given additional calcium.

With regard to several of these studies, questions were raised as to whether it was the vitamin D or the calcium in the treatment regimen that was responsible for the effect, but both the Chevalley study (which gave vitamin D to both treatment groups) and a recent study by Peacock et al. [17] showed that the bone-sparing effect was largely due to the supplemental calcium. However, the subjects in the Peacock study were, on entry, substantially closer to vitamin D repletion than were those studied by Chapuy et al., so one cannot exclude the possibility that some of the effect in the French trial was due to vitamin D as well as to calcium.

Total calcium intakes in the supplemented groups in these and most other trials ranged between 32.5 and 42.5 mmol (1300 and 1700 mg)/day, values that coincide remarkably closely with the findings from balance studies of Heaney and Recker [18] and with the recommendation of the NIH Consensus Development Conference on Optimal Calcium Intake [4].

	WHY THE REQUIREMENT APPEARS TO INCREASE WITH AGE

TOP ABSTRACT INTRODUCTION PHYSIOLOGICAL BASIS OF THE... BONE MASS, BONE STRENGTH... BONE STRENGTH AND CALCIUM... WHY THE REQUIREMENT APPEARS... NUTRIENT DEFICIENCY VS. CHRONIC... SYNTHESIS AND RECOMMENDATIONS REFERENCES

 
Several factors that accompany aging contribute both to age-related bone loss and to an increase in the calcium intake requirement. Contributing to the former is a decline in mechanical loading of the skeleton, both because of decreased physical activity and because of decreased skeletal muscle mass. Contributing to an increase in the requirement are declines in intestinal mucosal mass and in dermal synthesis of vitamin D. Both reduce calcium absorption efficiency. The decline in vitamin D production is because of decreased solar exposure and decreased efficiency of photochemical conversion of 7-dehydrocholesterol to pre-vitamin D [19]. Additionally, 1--hydroxylation of 25(OH)D at the kidney, in response to PTH secretion, also falls off with age [20]. Finally, in the absence of estrogen in postmenopausal women (and in many older men, as well), renal calcium conservation and intestinal calcium absorption efficiencies decline. All these changes work to produce a deterioration in efficiency of food calcium utilization. To make matters worse, food calcium intake itself tends to drop with age. Clearly, if an elderly individual is to offset ongoing obligatory losses through skin, digestive secretions and urine, calcium intake must rise, not fall.

The mechanisms that help humans adapt to low calcium intake are well studied and understood. They consist, first, of an increase in the secretion of parathyroid hormone (PTH). PTH initiates a series of mutually independent events that, in the aggregate, counteract the age-related changes just described: increased absorptive extraction from the digestate in the intestine, improved renal conservation and withdrawal of calcium from the skeletal reserves to make up for what the other two effects cannot accomplish. The mechanism by which PTH enhances intestinal absorptive efficiency is stimulation of 1--hydroxylation of 25(OH)D to the active form of the vitamin. As already noted, that conversion, as well as the other adaptive mechanisms, becomes less efficient with age.

Under primitive conditions, consuming enough food to maintain the physical activity of a hunter-gatherer existence would have ensured a calcium intake that would today seem high, probably in excess of 50 mmol (2000 mg)/day (and perhaps substantially more than that). Under such circumstances, conservation of calcium is not necessary, and much of the absorption through the intestinal tract would be by the passive route. Human physiology is fine-tuned to avoid calcium intoxication, not to deal with chronic scarcity. For our hominid and hunter-gatherer forebears, enhanced active intestinal transport and renal conservation were necessary and appropriate only during times of food shortage.

Once the age-related deterioration in calcium conservation is recognized, it becomes clear that the reason the requirement for calcium appears to rise in the elderly is that the ability to adapt to a low calcium intake declines. I deliberately use the word "appears" for the rise in the requirement because, in a sense, what is revealed in the elderly is a dependence upon the intake which they, and adults of all ages, would have received under primitive circumstances. The requirement in the elderly can, therefore, be best understood as the intake optimal for everyone, i.e., the intake that maintains the skeletal reserve without the need for constant adaptation to low intake. When we say that the requirement increases with age, what we must mean is that the ability to compensate for an inadequate intake falls. In brief, the least we can get by on rises as we age.

Although the term "minimum daily requirement (MDR)" is uncommonly encountered in the nutrition literature today, that is literally what current calcium recommendations amount to—the least an individual can get by on for a given functional indicator (in this case maintenance of skeletal mass). It should not, therefore, be surprising that intakes below the MDR for bone may express themselves also in multi-system dysfunctions.

This conceptual approach leads, inevitably, to the question whether the need to evoke constant adaptation is consistent with optimal health, even for younger adults who may be able to maintain skeletal balance on lower intakes. It would seem that a strong case could be made for the fact that it is not. In addition to the nonskeletal costs of low calcium intake (increases in risk of hypertension, obesity, premenstrual syndrome, colon cancer and kidney stones, among others [21]), apparently successful adaptation (in terms of sustaining the size of the calcium reserve) nevertheless has negative strength effects even on the skeleton itself. For example, high levels of PTH are associated with elevated levels of bone remodeling, and bone remodeling rate is now a recognized fragility factor, altogether apart from bone mass [22]. In fact, the fracture reduction that has been reported for newly developed pharmacologic therapies of osteoporosis [23–25] is now considered to be due in substantial measure to the reduction in bone remodeling which these agents produce. This is shown, among other ways, by the fact that the full fracture reduction is achieved for several of the agents by the end of one year of treatment, well before the full treatment-induced increase in bone mass is realized.

McKane et al. [26] in a double-blind calcium supplementation study of healthy elderly women treated with calcium intakes of either 20 mmol (800 mg)/day or 60 mmol (2400 mg)/day, found elevated levels of parathyroid cell mass, circulating PTH and bone remodeling in women ingesting the lower calcium intake, relative to healthy young adult women. By contrast, the women given the higher calcium intake for three years had a reversion to young adult normal values for all three indices of calcium homeostasis. Furthermore, chronic, years-long stimulation of parathyroid secretion is probably partly the explanation for the postmenopausal rise in the incidence of hyperparathyroidism in women. In population-based studies from Sweden [27], it has been shown that the incidence of hypercalcemia in postmenopausal women rises by a factor of 30x with age after menopause, while it does not change with age in men. This finding probably reflects the development over time of autonomous parathyroid cell clones with an abnormal calcium setpoint, arising because of life-long, chronic stimulation of parathyroid cell hyperplasia.

	NUTRIENT DEFICIENCY VS. CHRONIC DISEASE

TOP ABSTRACT INTRODUCTION PHYSIOLOGICAL BASIS OF THE... BONE MASS, BONE STRENGTH... BONE STRENGTH AND CALCIUM... WHY THE REQUIREMENT APPEARS... NUTRIENT DEFICIENCY VS. CHRONIC... SYNTHESIS AND RECOMMENDATIONS REFERENCES

 
It has become fashionable in nutrition circles in recent years to make a distinction between the role of nutrients in preventing deficiency disease and their role in ensuring optimal health and reducing the burden of many chronic diseases. To a substantial extent, this is a distinction without a difference, and it may function primarily to paper over our decades-long failure to use modern diagnostic and physiologic insights to identify real deficiency states. Because of different sizes of the nutrient reserves and different rates of consumption of the nutrients concerned, the time between beginning an inadequate intake and the expression of deficiency disease varies widely. With water soluble vitamins, disease can manifest itself within weeks, with fat soluble vitamins, months, but with minerals and particularly calcium (the reserve for which is the largest of any nutrient), the same outcome may require years. As should be evident, there is no apparent reason to characterize the disease expression produced by these varied nutrient inadequacies by any word other than "deficiency." The latency period is quite irrelevant.

At the same time it is important to recognize that there are only a limited number of ways that any organ or organ system can fail, although there may be a great many different mechanisms leading to such failure. Osteoporosis, hypertension, colon cancer and the other disorders linked to low calcium intake are all in that sense highly multifactorial. While osteoporosis represents mechanical failure of the skeleton, it has many causes, of which depletion of skeletal mass because of calcium deficiency is but one. Nevertheless, as noted already, in Europe and North America, it appears to be a common cause, since increasing calcium intake has an appreciable effect on fracture risk in the elderly.

	SYNTHESIS AND RECOMMENDATIONS

TOP ABSTRACT INTRODUCTION PHYSIOLOGICAL BASIS OF THE... BONE MASS, BONE STRENGTH... BONE STRENGTH AND CALCIUM... WHY THE REQUIREMENT APPEARS... NUTRIENT DEFICIENCY VS. CHRONIC... SYNTHESIS AND RECOMMENDATIONS REFERENCES

 
Elevating the daily calcium intake of the over-65 population will reduce osteoporotic fracture risk by from 30% to 50%. Precisely how high that intake should be is uncertain, since dose ranging studies of anti-fracture efficacy have not been performed. Because of their cost, such studies are unlikely ever to be done. Anti-fracture efficacy has been demonstrated for intakes in the range of 32.5–42.5 mmol (1300–1700 mg)/day. Whether a greater reduction could be achieved with even higher intakes or whether ensuring higher intakes earlier in life would produce a greater reduction still, is simply not known.

As already noted, reversion of parathyroid secretory dynamics and of bone remodeling level to young adult values has been reported for an intake of 60 mmol (2400 mg)/day, but whether the same effect might have been produced at a somewhat lower intake is also unknown. However, primitive human diets would have exhibited calcium nutrient densities on the order of 1.5 to 2.5 mmol/100 kCal, and diets today with similar densities would approximate the supplemented intake levels found in controlled trials to be efficacious in fracture risk reduction. Hence, even the seemingly high intakes of supplementation trials are not high in an historical or evolutionary sense.

For a 2000 kCal energy expenditure per day, a density of 2 mmol/100 kCal translates to a calcium intake in the range of 40 mmol (1600 mg)/day. With lower energy expenditures, diet density may need to be higher than the primitive average if the diet is to provide an absolute intake of 40 to 50 mmol. At the same time it should be understood that low energy expenditure means reduced work and a corresponding tendency to disuse bone loss. Calcium, no matter how high the intake, will not prevent that outcome.

Clearly food sources provide the best way to get this needed calcium, mainly because bone health, like total body health, is not a mono-nutrient issue. Foods, particularly dairy foods, constitute good sources of other essential nutrients, such as phosphorus, protein, vitamin D, B₁₂, magnesium and potassium, for all of which the diets of the elderly are often inadequate. Milk is particularly attractive, not only because it provides all of these other nutrients, but because its calcium comes at a negative cost. This is because milk is less expensive per calorie than the average food in an older person’s diet. Thus getting milk calcium actually costs less than not getting it—at the dinner table, not just later at the emergency room.

It is important to stress that the advantages of dairy products are as fully accessible to adult blacks and Asians as they are to Caucasians, despite the high prevalence of lactase non-persistence in non-Caucasian adults. A large body of evidence demonstrates conclusively that individuals habituated to milk can consume it in large quantities without symptoms, irrespective of their intestinal expression of lactase [28]. There are several explanations for this seeming paradox. To begin with, symptoms of lactose intolerance are only loosely correlated with absence of lactase. Second, habitual milk drinkers develop an intestinal flora with its own lactase; hence, the individual may not be lactase deprived even if his or her own mucosa fails to make the enzyme.

Green leafy vegetables of the cruciferous variety (mustard greens, collards, bok choy and the like) are also excellent calcium sources, because of both relatively high calcium nutrient densities and excellent bioavailability. They also constitute a good source of potassium and B-vitamins, and they have a net alkaline ash characteristic, which may be osteoprotective in its own right [29–31]. Additionally, there are a growing number of calcium-fortified foods and a large number of well-formulated calcium supplements available. Fortification can usually be accomplished at negligible cost to the food manufacturer, so a calcium-enriched food confers added value without significant additional cost. Thus, reaching the desired target of 40 mmol/day should be both relatively inexpensive and easy to accomplish at a population level.

In summary, the calcium intake that reduces fracture risk in the elderly is close to the actual, normal intake for all adults living in the conditions in which human physiology has evolved. It is, not surprisingly, the intake that also minimizes the expression of other disorders now shown to be aggravated by contemporary calcium intakes. The nutrition community has been slow to recognize that the multiple system manifestations of insufficient calcium intake constitute a true deficiency syndrome.

	FOOTNOTES

 
Presented in part at the 41st Annual Meeting of the American College of Nutrition at Las Vegas, Nevada, October 12–15, 2000.

Received November 22, 2000.

	REFERENCES

TOP ABSTRACT INTRODUCTION PHYSIOLOGICAL BASIS OF THE... BONE MASS, BONE STRENGTH... BONE STRENGTH AND CALCIUM... WHY THE REQUIREMENT APPEARS... NUTRIENT DEFICIENCY VS. CHRONIC... SYNTHESIS AND RECOMMENDATIONS REFERENCES

 

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