L. Gehrig, J. Lane, M.I. O'Connor, D. Zackson, and N. Karkare reply:
While we tried to provide a thorough review of the treatment of osteoporosis, we recognize that there are still many areas of controversy. What has been agreed on, however, is the importance of adequate calcium intake. We greatly appreciate Dr. Heaney's highlighting of the topic of calcium absorption from calcium salts.
With regard to the issue of whether calcium carbonate or calcium citrate is the preferred preparation, calcium carbonate has the highest concentration of calcium by weight (40%) among available oral calcium preparations and this property does reduce the number of pills needed per day. Calcium carbonate preparations are also cheaper than the ones containing calcium citrate. However, the literature on oral calcium preparations, including a meta-analysis1, supports the superiority of calcium citrate over calcium carbonate preparations. The values for absorption of calcium citrate have been consistently reported to be higher than those for absorption of calcium carbonate (even if the numerical differences in these absorption values have been small).
Patients presenting with osteoporosis may have asymptomatic gastric hypochlorhydria or achlorhydria, or these disorders may subsequently develop. The use of calcium carbonate by individuals with physiologically or pharmacologically reduced gastric acid levels can result in suboptimal calcium absorption because calcium carbonate requires a low pH for dissociation, whereas calcium citrate dissociates adequately even when the gastric pH is not in a low range. While coingestion with food enhances the bioavailability of both salts, calcium citrate is better absorbed than calcium carbonate when taken on an empty stomach or with meals1. As a dietary supplement, calcium carbonate may not be ideal for older persons2.
The incidence of kidney stones is indeed reduced with intake of all forms of calcium. However, it is important to note that citrate is an important inhibitor of calcium salt crystallization in the urine. While the mechanism of action for prevention of urolithiasis and the exact series of events that transform supersaturation to crystal formation and renal stones are complex3,4, supplementation with calcium citrate does not increase the risk of stone formation5. The incidence of calcium kidney stones is generally not increased because ionic calcium (introduced into the gut) binds with intraluminal oxalate (from food), producing a relatively insoluble calcium-oxalate complex that is less readily absorbed. Indeed, since oxalate is much more lithogenic than an equivalent molar amount of calcium, a standard therapeutic approach in the treatment of intestinal hyperoxalosis is to have the patient ingest large amounts of calcium (from calcium carbonate or calcium citrate), thus radically decreasing the percentage gut absorption of oxalate. However, calcium citrate is preferred to calcium carbonate in patients wth recurrent calcium-stone formation6,7. Although both forms of calcium can elevate urine calcium levels, urine citrate levels are elevated by calcium citrate, and citrate is strongly antilithogenic. The facts about elevation of urinary citrate levels from calcium carbonate have not been as well investigated. A patient who has had recurrent calcium kidney stones but requires substantial calcium loading (e.g., who has a normal serum calcium level but an elevated parathyroid hormone level signifying secondary hyperparathyroidism triggered by a negative calcium balance) can be given thiazides along with calcium citrate and can restrict sodium intake as well. Such manipulations rapidly lower urinary calcium levels and have a strong protective antilithogenic effect.
Numerous factors, including patient characteristics such as age, period of lactation, growth, type of diet (amount of fiber and oxalate), type of calcium supplementation, mental and physical stress, medications that impede calcium absorption, and medical conditions (lactose intolerance or impaired gastric secretion), affect the absorption of calcium8. A patient may present with a combination of morbidities. It is crucial that the health-care provider optimize calcium intake at the earliest opportunity without getting lost in the maze of conditions affecting absorption. Measurement of the serum calcium level at the onset will help to identify patients with hypercalcemia (primary hyperparathyroidism or sarcoidosis) for referral to a metabolic bone specialist for further evaluation. We believe that, after consideration of the costs and benefits, calcium citrate has a marginally superior absorption and protection profile.
These letters originally appeared, in slightly different form, on . They are still available on the web site in conjunction with the article to which they refer.