Reduction in the Size of the Nutrient Reserve
As noted earlier, bone is the body's calcium reserve, and mechanisms designed to protect ZCF [Ca2+] tear down bone to scavenge its calcium when excretory and dermal losses exceed absorbed dietary intake. In providing the calcium needed to maintain critical body fluid ncentrations, the reserve is functioning precisely as it should. But sooner or later there :taB to be payback, or the reserve becomes depleted, with an inescapable weakening of skeletal structures. During growth, on any but the most severely restricted of intakes, some bony
ccumulation does occur, but the result is usually failure to achieve the full genetic potential ·or bone mass. Later in life, the result is failure to maintain the mass achieved. As also noted earlier, both osteoporotic fractures and low bone mass have many causes other than low calcium intake.
Nevertheless, under 'prevailing conditions in the industrialized nations at high latitudes, the effect size for calcium is large. Calcium supplemented trials, even of short duration, have resulted in 30+% reductions in fractures in the elderly. In addition to the effect size's being large, the evidence for calcium's role is itself very strong. There have been roughly 50 published reports of investigator-controlled increases in calcium intake with skeletal endpoints, most of them randomized controlled trials and most of them published since 1990. All but two demonstrated either greater bone mass gain during growth, reduced bone loss with age, and! or reduced osteoporotic fractures.
The sole exceptions among these studies were a supplementation trial in men in which the calcium intake of the control group was itself already high (nearly 1200 mg/d), and a study confined to early postmenopausal women in whom bone loss is known to be predominantly due to estrogen deficiency. Complementing this primary evidence are roughly 80 observational studies testing the association of calcium intake with bone mass, bone loss, or fracture. It has been shown elsewhere that such observational studies are inherently weak, not only for the generally recognized reason that uncontrolled or unrecogI1ized factors may produce or obscure associations between the variables of interest, but because the principal variable in this case, lifetime calcium intake, cannot be directly measured and must be estimated by dietary recall methods.
The errors of such estimates are immense and have been abundantly documented. 'Their effect is to bias all such investigations toward the null. Nevertheless, more than three-fourths of these observational studies reported a significant calcium benefit. Given the insensitivity of the method, the fact. th.i:it most of these reports are positive emphasizes the strength of the association; at the same time, it provides reassurance that the effects achievable in the artificial context of a dinidl trial can be observed in real world settings as well.
Calcium is a unique nutrient in several respects. It is the only nutrient for which the reserve has required an important function in its own right. We use the reserve for structural support, i.e., we literally walk on our calcium nutrient reserve. Calcium is unique also in that our bodies cannot store a surplus, unlike, for example, energy or the fat-soluble vitamins. Calcium is stored not as such but as bone tissue, and regulation of bone mass is cell mediated, with the responsible bone cellular apparatus controlled through a feedback loop regulated by mechanical forces.
In brief, given an adequate calcium intake, we have only as much bone as we need for the loads we currently sustain. These features are the basis for the designation of calcium as a threshold nutrient with respect to skeletal status, a term that means that calcium retention rises as intake rises, up to some threshold value that provides optimal bone strength; then, above that level, increased calcium intake produces no further retention and is simply excreted. This threshold intake is the lowest intake at which retention is maximal, i.e., it is the minimum daily requirement (MDR) for skeletal health. The MDR varies with age, and is currently estimated to be about 20 - 25 mraol (800 - 1000 mg)/d during childhood, 30 - 40 mmol (1200 - 1600 mg)/d during adolescence, approx 25 mmol (1000 mg)/d during the mature adult years, and 35 - 40 mmol (1400 - 1600 mg)/d in the elderly.
As previously noted, the rise in the requirement in old age reflects a corresponding decline in ability to adapt, i.e., to respond to low intakes with improved absorption and retention. At the same time, as already noted, osteoporosis is a distinctly multifactorial disorder, both in the sense that many factors contribute to bone loss and fracture risk, and also in the sense that yet other factors influence the body's handling of calcium. Of most importance in the latter respect are dietary factors such as caffeine, which reduces calcium absorption very slightly, and protein and sodium, both of which increase urinary calcium loss. The urinary effects are the larger, but for all three nutrients, the impact on the calcium economy disappears at high calcium intakes (40 mmol/d or above). As already noted, such intakes, although high by today's standards, are typical of the paleolithic intake. The behaviour of the calcium homeostatic system in response to a challenge such as sodium or protein-induced hypercalciuria illustrates beautifully how the fine tuning of the calcium economy presumes a high intake. A provoked increase in urinary calcium loss, if not offset, leads to a fall in ECF [Ca2+], which evokes an increase in PTH and in 1, 25(OH)2D levels. These hormones act on bone as well as on the gut, and it is the combined response of both effector organs that offsets the drop in ECF [Ca2+].
However, the balance between the bone and dietary components of this response depends entirely on the calcium content of the diet. For example, the increase in 1, 25 OH)2D evoked by a 1 mmol/d additional loss of calcium leads to an increase in absorption efficiency of 1.5 2.0 absorption percentage points. At an intake of 50 mmol/d, that absorptive increase is entirely adequate to compensate for the additional urinary loss. On the other hand, at intakes such as those at the bottom quartile in NHANES-III (National Health and Nutrition Examination Survey), the absorptive increase offsets less than one-eighth of the urinary ~aIcium loss. The rest must come from bone. Of the factors that influence bone more directly (rather than by way of the calcium economy), one can list smoking, alcohol abuse, hormonal status, body weight, and exercise.
Smoking and alcohol abuse exert slow, cumulative effects by uncertain mechanisms that suIt in reduced bone mass and increased fracture risk. Low estrogen status and .yperthyroidism produce similar net effects, although probably by very different mechanisms. Bone mass rises directly with body weight, again by uncertain mechanisms.
Exercise, particularly impact loading, is osteotrophic and is important both for building optimal bone mass during growth and for maintaining it during maturity and senescence. In a sense, bone health is like a three-legged stool; one leg is nutrition, another is hormones, and the third is lifestyle. All three legs must be strong if the stool (or the skeleton) is to support us. Strengthening of one leg will not compensate for weakness of another.
