Chronic proton pump inhibitor (PPI) use has been linked to an increased risk of hip, wrist, and spine fractures. This is because acid suppression is associated with a reduction in calcium absorption, which can lead to decreased bone density.1,2
By creating an environment without acid, there is a significant increase in pH that may affect intestinal absorption of calcium and result in a negative calcium balance within the body. However, a single post-hoc analysis involving patients on calcium supplements varying in solubility revealed that the relationship between solubility and absorption was weak.2
This analysis showed that calcium absorption is more dependent on components of coingested foods than pH solubility.2 On the other hand, some data suggest that calcium absorption is significantly dependent on gastric pH.1
Calcium is primarily absorbed in its ionized form in the upper small intestine. Highly acidic environments, such as the gastric environment, help promote calcium ionization from foods or salt forms.1 The major difference between calcium supplements tends to be the salt forms.

Calcium carbonate is an insoluble salt form, while calcium citrate is a soluble salt form.2,3 Insoluble calcium salts require a lower pH to help facilitate the release of ionized calcium from the complex.1,3 Patients taking PPIs may have issues absorbing an optimal amount of calcium from insoluble salt forms, such as calcium carbonate.
Results of a study comparing the absorption of calcium at different pHs indicated that patients in the fasting state had impaired absorption of calcium from calcium carbonate but normal absorption from calcium citrate.2 Calcium citrate also had a 46% greater peak-basal variation and a 94% greater change in AUC for serum calcium compared with calcium carbonate.3
Additional benefit from calcium citrate use was a significant reduction in serum parathyroid hormone (PTH) levels from baseline. This informs us that the calcium absorption was significant enough to reduce PTH activity and diminish bone resorption.3

Calcium carbonate may be used in patients on chronic PPIs, but it must be taken with a meal to promote acid production; however, the amount of calcium absorbed is still less than what is absorbed from calcium citrate.2
Because calcium citrate is not dependent on acid or pH for absorption, it may be the preferred calcium supplement for PPI users.
Calcium citrate supplements and calcium in natural products such as cheese and milk will provide patients with greater bioavailability regardless of pH. Therefore, calcium citrate should be recommended over calcium carbonate.2
If a patient cannot afford calcium citrate, however, they can use calcium carbonate as long as they are properly counseled to take it with meals (specifically breakfast) to promote better absorption.
Based on current research, no clinical evidence suggests that calcium citrate is superior to calcium carbonate in terms of preventing osteoporosis-related fractures in patients on chronic PPI therapy.

1. Ito T, Jensen RT. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Curr Gastroenterol Rep. 2010;12(6):448-457.
2. Hansen KE, Jones AN, Lindstrom MJ, et al. Do proton pump inhibitors decrease calcium absorption? J Bone Miner Res. 2010;25(12):2786-2795.
3. Yang YX. Chronic proton pump inihibitor therapy and calcium metabolism. Curr Gastroenterol Rep. 2012;11(6):173-179.