Calcium metabolism

  Calcium metabolism or calcium homeostasis is the mechanism by which the body maintains adequate calcium levels. Derangements of this mechanism lead to hypercalcemia or hypocalcemia, which both can have important consequences for health.

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Calcium location and quantity

Calcium is the most abundant mineral in the human body. The average adult body contains in total approximately 1 kg, 99% in the skeleton in the form of calcium phosphate salts. The extracellular fluid (ECF) contains approximately 22.5 mmol, of which about 9 mmol is in the serum. Approximately 500 mmol of calcium is exchanged between bone and the ECF over a period of twenty-four hours.^[1]

Normal ranges

The serum level of calcium is closely regulated with a normal total calcium of 2.2-2.6 mmol/L (9-10.5 mg/dL) and a normal ionized calcium of 1.1-1.4 mmol/L (4.5-5.6 mg/dL). The amount of total calcium varies with the level of serum albumin, a protein to which calcium is bound. The biologic effect of calcium is determined by the amount of ionized calcium, rather than the total calcium. Ionized calcium does not vary with the albumin level, and therefore it is useful to measure the ionized calcium level when the serum albumin is not within normal ranges, or when a calcium disorder is suspected despite a normal total calcium level.

Corrected calcium level

One can derive a corrected calcium level when the albumin is abnormal. This is to correct for the change in total calcium due to the change in albumin-bound calcium, and gives an estimate of what the calcium level would be if the albumin were within normal ranges.

Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 4.0 represents the average albumin level.

When there is hypoalbuminemia (a lower than normal albumin), the corrected calcium level is higher than the total calcium.

Effector organs

Sources

About 25 mmol of calcium enters the body in a normal diet. It can be lower if the diet is low in leafy green vegetables, legumes, or other calcium-containing substances. Of this, about 40% (10 mmol) is absorbed in gut, and 5 mmol leaves the body in feces, netting 5 mmol of calcium a day. Vitamin D is an important co-factor in the intestinal absorption of calcium, as it increases the number of calcium binding proteins, involved in calcium absorption through the apical membrane of enterocytes in small intestine.

Excretion

The kidney excretes 250 mmol a day in pro-urine, and resorbs 245 mmol, leading to a net loss in the urine of 5 mmol/l. In addition to this, the kidney processes Vitamin D into calcitriol, the active form that is most effective in assisting intestinal absorption. Both processes are stimulated by parathyroid hormone.

The role of bone

Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Calcium is released from bone by parathyroid hormone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin.

Low calcium intake may also be a risk factor in the development of osteoporosis. In one meta-analyses, the authors found that only two out of the 52 studies that they reviewed showed that calcium intake did not promote better bone balance.^[2] With a better bone balance, the risk of osteoporosis is lowered.

Regulatory organs

Primarily calcium is regulated by the actions of Vitamin D, parathyroid hormone and calcitonin. The only real regulatory organ is the parathyroid gland. The parathyroid glands are located behind the thyroid, and produce parathyroid hormone in response to low calcium levels.

The parafollicular cells of the thyroid produce calcitonin in response to high calcium levels, but its significance is much smaller than that of PTH.

Pathology

Hypocalcemia and hypercalcemia are both serious medical disorders.

Renal osteodystrophy is a consequence of chronic renal failure related to the calcium metabolism.

Osteoporosis and osteomalacia have been linked to calcium metabolism disorders.

Research into cancer prevention

The role that calcium might have in reducing the rates of colorectal cancer has been the subject of many studies. However, given its modest efficacy, there is no current medical recommendation to use calcium for cancer reduction. Several epidemiological studies suggest that people with high calcium intake have a reduced risk of colorectal cancer. These observations have been confirmed by experimental studies in volunteers and in rodents. One large scale clinical trial shows that 1.2 g calcium each day reduces, modestly, intestinal polyps recurrence in volunteers.^[3] Data from the four published trials are available.^[4] Some forty carcinogenesis studies in rats or mice, reported in the Chemoprev.Database, also support that calcium could prevent intestinal cancer.^[5]

References

1. ^ Marshall, W. J. 1995. Clinical Chemistry, 3rd ed. Mosby, London.
2. ^ Heaney, R. P., et al. Calcium, dairy products and osteoporosis. J Am Coll Nutr. 2000 Apr;19(2 Suppl):83S-99S.
3. ^ Baron J, Beach M, Mandel J, van Stolk R, Haile R, Sandler R, Rothstein R, Summers R, Snover D, Beck G, Bond J, Greenberg E (1999). "Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group". N Engl J Med 340 (2): 101-7. PMID 9887161.
4. ^ http://www.inra.fr/reseau-nacre/sci-memb/corpet/Data/table.php?file=Potency-Man.txt
5. ^ http://www.inra.fr/reseau-nacre/sci-memb/corpet/MAcalcium.html