TABLE 1

Vitamin D Deficiency: Stages and Clinical Signs

1. Stages of vitamin D deficiency
    Stage I
        25-OH-D level decreases, resulting in hypocalcemia and euphosphatemia; 1,25-OH2-D may increase or remain unchanged
    Stage II
        25-OH-D level continues to decrease; PTH acts to maintain calcium through demineralization of bone; the patient remains eucalcemic and hypophosphatemic and has a slight increase in the skeletal alkaline phosphatase level
    Stage III
        Severe 25-OH-D deficiency with hypocalcemia, hypophosphatemia, and increased alkaline phosphatase; bones have overt signs of demineralization
2. Clinical signs of vitamin D deficiency
    • Dietary calcium absorption from the gut decreases from 30%–40% to 10%–15% when there is vitamin D deficiency
    • Low concentrations of 25-OH-D trigger the release of PTH in older infants, children, and adolescents in an inverse relationship not typically seen with young infants; the increase in PTH mediates the mobilization of calcium from bone, resulting in a reduction of bone mass; as bone mass decreases, the risk of fractures increases
    ○ Rickets
        Enlargement of the skull, joints of long bones, and rib cage; curvature of spine and femurs; generalized muscle weakness
    ○ Osteomalacia and osteopenia
    ○ Abnormal immune function with greater susceptibility to acute infections and other long-latency disease states (see below)
3. Potential latent disease processes associated with vitamin D deficiency
    • Dysfunction of the innate immune system is noted with vitamin D deficiency
        ○ Immunomodulatory actions may include
            • Potent stimulator of innate immune system acting through Toll-like receptors on monocytes and macrophages
            • Decrease threshold for long-latency diseases such as cancers (including leukemia and colon, prostate, and breast cancers), psoriasis, diabetes mellitus, and autoimmune diseases (eg, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosis)