25-OH-D level decreases, resulting in hypocalcemia and euphosphatemia; 1,25-OH2-D may increase or remain unchanged
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
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
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)
Oral Vitamin D Preparations Currently Available in the United States (in Alphabetical Order)
Multivitamin preparations: polyvitamins (A, D, and C vitamin preparations)c
1 mL contains 400 IU; variable preparations that include glycerin and water; may also contain propylene glycol and/or polysorbate 80
Note that higher-dose oral preparations may be necessary for the treatment of those with rickets in the first few months of therapy or for patients with chronic diseases such as fat malabsorption (cystic fibrosis) or patients chronically taking medications that interfere with vitamin D metabolism (such as antiseizure medications).
↵a A study by Martinez et al162 showed that newborn and older infants preferred oil-based liquid preparations to alcohol-based preparations.
↵b Single-drop preparation may be better tolerated in patients with oral aversion issues, but proper instruction regarding administration of these drops must be given to the parents or care provider, given the increased risk of toxicity, incorrect dosing, or accidental ingestion.
↵c The cost of vitamin D–only preparations may be more than multivitamin preparations and could be an issue for health clinics that dispense vitamins to infants and children. The multivitamin preparation was the only preparation available until recently; therefore, there is a comfort among practitioners in dispensing multivitamins to all age groups.