Hypocalcemia

Humans, like all vertebrates, require calcium for signal and muscle contraction, and to build and maintain skeletons. We also need vitamin D to maintain calcium homeostasis, as outlined in Lyman's (1) review of vitamin D deficiency among hospitalized patients in this issue of American Family Physician.

When the human body is deficient in vitamin D because of reduced dietary intake or inadequate exposure to sunlight, the parathyroid hormone mobilizes calcium from its stores in the skeleton to restore calcium balance in the blood. While this action prevents the usual manifestations of hypocalcemia until vitamin D deficiency is quite severe, adults who are deficient in vitamin D may have chronic pain and lower extremity weakness. Indeed, women who are deficient in vitamin D often are misdiagnosed with fibromyalgia or even somatization syndromes. (2)

Physicians often do not consider vitamin D deficiency as a cause of hypocalcemia or unexplained weakness, even in patients at high risk for vitamin D deficiency (e.g., older adults, homebound patients).

Technically, vitamin D is not a vitamin but a steroid hormone that stimulates the vitamin D receptor in the cell nucleus to upregulate gene expression. The result of this stimulation is an increase in the absorption of calcium from the small intestine. Without adequate vitamin D, the body absorbs no more than 15 percent of dietary calcium. With sufficient vitamin D, calcium absorption increases to 30 percent and, during pregnancy or lactation and in periods of growth, absorption can approach 80 percent. (3)

One reason physicians discount the possibility of vitamin D deficiency is that they assume their patient has had plenty of sun exposure or adequate dietary intake. However, many patients actively avoid the sun or scrupulously use sunscreen in an effort to reduce their risk of developing skin cancer. In addition, as some patients age and become more homebound, they do not go out in the sun as much. A further complication is that sunlight in most of the United States (i.e., those states farther away from the equator) is inadequate to stimulate enough vitamin D formation in the winter. Persons most prone to chronic illness (e.g., older adults and those with impaired mobility from chronic diseases) are much less likely to get enough sun exposure to synthesize sufficient vitamin D.

Dietary sources of vitamin D are tougher to come by than most physicians realize. Although fatty fish, such as salmon and mackerel, contain large amounts of vitamin D, and milk is fortified with vitamin D, most foods, including human breast milk, contain very little vitamin D. The American Academy of Pediatrics issued new guidelines in 2003 recommending vitamin D supplementation for breastfed infants. (4)

Some people take in more vitamin D than is recommended and still are deficient in vitamin D. The results of one study (5) of patients in a Boston hospital showed that 37 percent of those with intakes exceeding recommended amounts had subnormal 25-hydroxyvitamin D levels.

When reduced sun exposure is combined with inadequate dietary intake, vitamin D deficiency is found to be much more widespread than previously was thought. The prevalence of vitamin D deficiency has been reported to be as high as 21 to 58 percent in adolescents and adults in the United States (depending on age and gender), (6) 54 percent in homebound older adults, (7) and 84 percent in elderly black women. (3) When pregnant women (8) and breastfed infants (4) are included, it appears that virtually the entire continuum of patients that family physicians treat is at risk.

Physicians should consider checking serum 25-hydroxyvitamin D levels in patients at risk for deficiency and in those suspected of being deficient in vitamin D. This is the most reliable test for vitamin D status. Symptomatic patients, such as those with unexplained muscle weakness or pain (especially of the lower back or legs) also should be evaluated for vitamin D deficiency. It is important to note that many laboratories consider serum 25-hydroxyvitamin D levels to be subnormal only if the results are below 8 to 10 ng per mL (20 to 25 nmol per L). However, most endocrinologists believe that a normal level should be at least 20 ng per mL (50 nmol per L), and some experts advocate a level as high as 30 ng per mL (75 nmol per L). (3)

One hundred years ago, vitamin D deficiency, in the form of rickets, was epidemic in this country. Vitamin D deficiency nearly disappeared by the middle of the last century, but we now know that the spectrum of vitamin D deficiency is much broader and the prevalence of this disease much greater than had been believed. (9) The results of recent reports give physicians another opportunity to improve the well-being of many of our chronically ill patients.

REFERENCES

(1.) Lyman D. Undiagnosed vitamin D deficiency in the hospitalized patient. Am Fam Physician 2005;71:299-304.

(2.) Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 2003;78:1463-70.

(3.) Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes 2002;9:87-98.

(4.) Gartner LM, Greer FR, Section on Breastfeeding and Committee on Nutrition, American Academy of Pediatrics. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics 2003;111(4 pt 1):908-10.

(5.) Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, et al. Hypovitaminosis D in medical inpatients. N Engl J Med 1998;338:777-83.

(6.) Looker AC, Dawson-Hughes B, Calvo MS, Gunter EW, Sahyoun NR. Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone 2002;30:771-7.

(7.) Gloth FM 3d, Gundberg CM, Hollis BW, Haddad JG Jr, Tobin JD. Vitamin D deficiency in homebound elderly persons. JAMA 1995;274:1683-6.

(8.) Datta S, Alfaham M, Davies DP, Dunstan F, Woodhead S, Evans J, et al. Vitamin D deficiency in pregnant women from a non-European ethnic minority population--an interventional study. BJOG 2002;109:905-8.

(9.) Hickey L, Gordon CM. Vitamin D deficiency: new perspectives on an old disease. Curr Opin Endocrinol Diabetes 2004;11:18-25.

JAMES P. RICHARDSON, M.D., M.P.H., is chief of geriatric medicine at Union Memorial Hospital, and clinical professor of family medicine at the University of Maryland School of Medicine, both in Baltimore. He received his medical degree from the University of Maryland School of Medicine, and his master of public health degree from Johns Hopkins University School of Hygiene and Public Health, both in Baltimore. He completed a residency in family medicine at the University of Maryland. He has held a certificate of added qualifications in geriatric medicine since 1988.

Address correspondence to James P. Richardson, M.D., M.P.H., Union Memorial Hospital, 201 E. University Pkwy., Suite 415, Baltimore, MD 21218 (e-mail: james.richardson@medstar.net). Reprints are not available from the author.

JAMES P. RICHARDSON, M.D., M.P.H. University of Maryland School of Medicine Baltimore, Maryland

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