Causes of vitamin D deficiency and resistance
- Zalman S Agus, MD
Zalman S Agus, MD
- Emeritus Professor of Medicine and Physiology; Associate Dean, CME
- Perelman School of Medicine at the University of Pennsylvania
- Marc K Drezner, MD
Marc K Drezner, MD
- Section Editor — Bone Disease
- Professor of Medicine
- University of Wisconsin Medical School
Vitamin D has a variety of actions on calcium, phosphate, and bone metabolism. Its most important biological action is to promote enterocyte differentiation and the intestinal absorption of calcium and phosphorus, thereby promoting bone mineralization. At high vitamin D concentrations, under conditions of calcium and phosphate deficiency, it also stimulates bone resorption, thereby helping to maintain the supply of these ions to other tissues (figure 1). (See "Normal skeletal development and regulation of bone formation and resorption", section on 'Calcitriol'.)
Vitamin D deficiency or resistance interferes with these processes, sometimes causing hypocalcemia and hypophosphatemia. Since hypocalcemia stimulates the release of parathyroid hormone (PTH), however, the development of hypocalcemia is often masked. The secondary hyperparathyroidism, via its actions on bone and the kidney, partially corrects the hypocalcemia but enhances urinary phosphate excretion, thereby contributing to the development of hypophosphatemia and osteomalacia. (See "Epidemiology and etiology of osteomalacia" and "Clinical manifestations, diagnosis, and treatment of osteomalacia", section on 'Laboratory findings'.)
This topic will review the major causes of vitamin D deficiency and resistance. Optimal serum vitamin D concentrations, the treatment of vitamin D deficiency, and the role of vitamin D therapy for osteoporosis are discussed in detail separately. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment" and "Calcium and vitamin D supplementation in osteoporosis".) The major causes of hypophosphatemia and hypocalcemia are also reviewed elsewhere. (See "Causes of hypophosphatemia" and "Etiology of hypocalcemia in adults".)
The optimal serum 25-hydroxyvitamin D (25[OH]D) concentration for skeletal health and extraskeletal health is controversial, and it has not been rigorously established for the population in general or for specific ethnic groups. Clinicians variably consider the optimal serum 25(OH)D concentration to range between 20 and 40 ng/mL (50 to 100 nmol/L) or between 30 and 50 ng/mL (75 to 125 nmol/L). The range of common agreement is 30 to 40 ng/mL (75 to 100 nmol/L). This topic is reviewed in detail elsewhere. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Defining vitamin D sufficiency'.)
VITAMIN D METABOLISM
Vitamin D (cholecalciferol) is normally synthesized in the skin under the influence of sunlight in a nonenzymatic manner. In addition, vitamin D (ergocalciferol) may be ingested from fish or plant sources. Vitamin D is then hydroxylated in the liver to 25-hydroxyvitamin D (calcidiol, 25[OH]D), which is the major circulating form of vitamin D and the best index of vitamin D sufficiency. Calcidiol is hydroxylated primarily in the kidney to 1,25-dihydroxyvitamin D (calcitriol), which is the most active form (figure 1). 1,25-dihydroxyvitamin D is also formed in some other tissues but is used only within the tissues and not circulated. (See "Overview of vitamin D", section on 'Metabolism'.)
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- VITAMIN D METABOLISM
- NUTRITIONAL DEFICIENCY AND REDUCED CUTANEOUS SYNTHESIS
- Older adults
- Healthy adults in the winter
- Hospitalized patients
- Women treated for osteoporosis
- Chronic renal disease
- Gastrointestinal disease
- Gastric bypass
- Immigrants to cold climates from warm climates
- Patients who have musculoskeletal pain
- Cystic fibrosis
- Extensive burns
- DEFICIENCY RELATED TO ABNORMAL SYNTHESIS AND CATABOLISM
- Calcidiol (25-hydroxyvitamin D)
- - Decreased synthesis
- - Drugs
- - Renal loss
- Calcitriol (1,25-dihydroxyvitamin D)
- - Renal failure
- - Vitamin D dependent rickets type I
- VITAMIN D RESISTANCE
- INFORMATION FOR PATIENTS