An abnormally efficient intestinal absorption of diet calcium is well known in idiopathic hypercalciuria [3, 4], as well as in primary hyperparathyroidism, sarcoidosis, immobilization, and vitamin D intoxication (other reasonably common hypercalciuric stone-forming states) [2]. In the case of idiopathic hypercalciuria, hyperabsorption seemed the main, perhaps the only abnormality. Low-calcium diet, therefore, offered itself as a reasonable treatment, and such diets have long enjoyed popularity [5, 6]. But a number of problems have gradually emerged and have, by this time, pushed low-calcium diets out of favor. One problem is that no prospective, controlled trials have ever shown that dietary measures are effective in stone prevention, whereas thiazide diuretics, when used as long-term therapy, do prevent stones by decreasing urinary calcium excretion [7].

A second problem is that bone mineral is abnormally labile in patients with idiopathic hypercalciuria. Compared with normal persons, patients with this condition excrete an abnormally high fraction of their absorbed dietary calcium in the urine [8]. Low-calcium diets do not efficiently decrease urinary calcium levels in many patients [9], who can lose more calcium in their urine than they are eating at the time [9]. Bone mineral density tends to be below normal in a majority of stone-forming patients [8] and is closely connected with persistent hypercalciuria during fasting or a low-calcium diet. The lability of bone mineral is not explained, but may reflect abnormally prominent actions of calcitriol in some cases [10]. Because some but not all patients with idiopathic hypercalciuria lose bone mineral given a low-calcium diet, such a diet is not reasonable for many patients. Identifying patients whose bones might suffer from dietary calcium restriction adds troublesome complexity and expense to clinical practice and may not be feasible for physicians in general.

A third problem is reciprocal hyperoxaluria, well known with low-calcium diets [11]. Increased urinary oxalate levels can maintain calcium oxalate stone-forming potential, even as a low-calcium diet decreases urinary calcium levels. For example, extreme reduction of bioavailable diet calcium using sodium cellulose phosphate increases urinary oxalate and calcium oxalate supersaturation [12] despite a considerable decrease in urinary calcium levels. On the other hand, a low-calcium diet can reduce supersaturation of calcium oxalate in some patients, perhaps those whose bone mineral is not easily mobilized [13]. It is not entirely correct, therefore, to maintain that an increase in urinary oxalate levels always offsets lower urine calcium from restriction of dietary calcium. A better way to summarize these dietary effects is to say that the decrease in supersaturation may be blunted, or even prevented, by reducing calcium intake, but only among some patients. The problem is that identifying the right patients requires extra studies, an undertaking that may not always be practical.

The study by Curhan and colleagues in this issue [14] adds its welcome mote to a flood of negatives about low-calcium diets. Women consuming such diets seem more at risk for stones than those with higher calcium intakes, perhaps, as Curhan and colleagues speculate, because of reciprocal hyperoxaluria. The same inverse association between dietary calcium and risk for stone formation has been reported among men [15]. These findings are not of direct importance to patients who already form stones because current treatment recommendations in standard sources already lean toward medication and away from low-calcium diets [2, 8]. The more compelling problem may be among family members of stone formers, who decrease their calcium intake in order to ward off a familial "curse." On the basis of Curhan and colleagues' study and its predecessor [15], one might advise against such actions. In addition, one should lean toward adequate calcium intake (at least 800 mg/d and perhaps more) in stone formers receiving thiazide.

Curhan and colleagues' study also makes clear that calcium excess from supplements may cause trouble. Women who use supplements may be at higher risk for stones, perhaps because of timing. If supplementary calcium is taken between meals, oxalate absorption may not be properly suppressed, whereas boluses of calcium will be absorbed and cause urinary supersaturations to peak. Whatever the underlying mechanisms, one might take away the thought that dietary calcium sources are potentially safer, and certainly tastier, than supplementary sources for stone-forming patients.

As always, the glory and chief woe of epidemiology lie in its freedom from the narrowness of individual patient details. For example, thiazides, an important antistone remedy, are used commonly for hypertension and edema. Nobody knows how many patients in the group used thiazides or whether for some reason thiazide use was more common in women who consumed more calcium. Also speculative is the proposed mechanism of stones. Reciprocal hyperoxaluria can be demonstrated in laboratory experiments, but how robust it is clinically depends on the total diet and the bioavailability of dietary oxalate. In addition, reciprocal hyperoxaluria tends to maintain a high level of supersaturation despite a decreasing urinary calcium level but does not usually increase supersaturation above the level produced by a normal calcium intake. In other words, a low-calcium diet does not increase urine supersaturation even if it fails to decrease it.

The opposite effects of supplementary calcium and dietary calcium in Curhan and colleagues' study also remain an enigma. Perhaps the timing explanation is correct. Perhaps, in truth, dietary calcium is a proxy for some other dietary factors that are lithogenic or protective against stones and supplementary calcium is simply lithogenic in itself. On these issues, Curhan and colleagues' study is correctly silent.

In contrast, thiazide therapy is efficacious in reducing calcium stone formation and does not appear to pose any risk to bone. In fact, the mechanism of reduced urine calcium from thiazides is an apparent shunting of absorbed dietary calcium into bone [16], not a reduction in intestinal calcium absorption. This bone shunting is potentially beneficial to both bone density and stone disease. Of course, the well-known action of thiazides to increase fractional calcium reabsorption by the renal tubule [16] could not, alone, change total daily calcium excretion. When blood calcium levels are steady, the total daily calcium excretion must equal the difference between net intestinal calcium absorption and net bone calcium uptake. As one would expect from its bone actions, thiazides appear strongly associated with reduced bone fractures [17-19]. Thiazides may reduce loss of bone mineral by directly stimulating osteoblast activity [20].

The established place of thiazides and the drawbacks of low-calcium diets, coupled with modern sensibilities about a need for adequate calcium intake for bone (especially among women), have more or less ended the diet phase of clinical practice in favor of an old, inexpensive, and well-understood drug. Low-calcium diets have not retained their early appeal, and thiazides have present pride of place. We are thankful for Curhan and colleagues' study, which adds yet another reason why physicians should drop dietary calcium restriction from their list of preventive and therapeutic measures for patients who are at risk formation of calcium oxalate stones.