The majority of calcium in the body is present in bones. The remainder of the calcium is in serum and has various functions. For example, calcium ions decrease neuromuscular excitability, participate in blood coagulation, and activate some enzymes.

Hypercalcemia can result from hyperparathyroidism, hypervitaminosis D, multiple myeloma, and some neoplastic diseases of bone. Long-term lithium therapy has been reported to cause hyperparathyroidism in some individuals, with resulting hypercalcemia.

Hypocalcemia can result from hypoparathyroidism, hypoalbuminemia, renal insufficiency, and pancreatitis.

Increased urinary calcium excretion (hypercalciuria) is a known contributor to kidney stone disease and osteoporosis. Many cases are genetic (often termed "idiopathic"). Previously such patients were often divided into fasting versus absorptive hypercalciuria depending on the level of urine calcium in a fasting versus fed state, but the clinical utility of this approach is now in question. Overall, the risk of stone disease appears increased when 24-hour urine calcium is >250 mg in men and >200 mg in women. Thiazide diuretics are often used to reduce urinary calcium excretion, and repeat urine collections can be performed to monitor the effectiveness of therapy. Known secondary causes of hypercalciuria include hyperparathyroidism, Paget disease, prolonged immobilization, vitamin D intoxication, and diseases that destroy bone (such as metastatic cancer or multiple myeloma). Urine calcium excretion can be used to gauge the adequacy of calcium and vitamin D supplementation, for example in states of gastrointestinal fat malabsorption that are associated with decreased bone mineralization (osteomalacia).