Milk Alkali Syndrome and the Dynamics of Calcium Homeostasis

Abstract

Intensive treatment with calcium-containing antacids and milk first was used in the early 20th century for the treatment of peptic ulcer disease and sometimes was associated with toxicity, eventually known as the milk alkali syndrome. Despite the introduction of H2 blockers and proton pump inhibitors for the treatment of peptic ulcer disease, the milk alkali syndrome continues to occur but is seen more frequently in older women who are receiving treatment for osteoporosis. The milk alkali syndrome provides a unique opportunity to discuss calcium homeostasis in a setting in which the primary calcium regulatory hormones, parathyroid hormone (PTH) and calcitriol, are not overtly abnormal. A thorough understanding of the pathophysiology of the milk alkali syndrome, including its generation and maintenance, requires knowledge of intestinal calcium absorption, bone influx and efflux of calcium, and renal calcium excretion and also how these processes change with age. In this review, the pathophysiology of the milk alkali syndrome is discussed in light of recent advances in our understanding of calcium homeostasis, particularly the role of the calcium-sensing receptor (CaSR) and epithelial calcium channels that are present in various tissues such as the parathyroid gland, kidney, and intestine. The contributions of alkalosis, per se , to the generation and maintenance of hypercalcemia are discussed in detail. Almost 100 years ago, Sippy (1) developed a calcium-laden milk and antacid regimen for the treatment of peptic ulcer disease. His rationale was to neutralize the hyperacidity that was deemed responsible for peptic ulcer disease. The Sippy regimen was used for the treatment of peptic ulcer disease, a disorder that was most common in middle-aged men, until the 1970s, when nonantacid treatment first was introduced (2–4). The original recommendation by Sippy consisted of the hourly administration of milk and cream together with what became known as …