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Stages of Vitamin D Deficiency

1. Early in the disease, when 25(OH)D is low, the first biochemical manifestation is a small increase in parathyroid hormone. This is because the parathyroid gland is exquisitely sensitive to subtle decreases in calcium. This often occurs before plasma calcium is below the reference range. These patients can show osteopenia.

2. As the disease progresses and 25(OH)D is lower, parathyroid hormone increases more in an attempt to normalized calcium balance. This results in significant bone resorption of calcium and phosphate. Increased PTH-mediated calcium reabsorption in the kidney holds on to the calcium preventing significant hypocalcemia. However, the predominant phosphaturic effect of PTH results in hypophosphatemia despite increased phosphate resorption from bone. Mild rachitic changes can been found in bone.

3. When vitamin D deficiency is severe and long standing, patients have high PTH levels, low plasma calcium and phosphate, and severe bone disease (rickets in children; osteomalacia in adults).

Source: Levine M, Zapalowski C, Kappy M. Disorders of calcium, phosphate, PTH and vitamin D metabolism. In: Kappy MS, Allen DB, Geffner ME, eds. Principles and Practice of Pediatric Endocrinology.Springfield,IL: Charles C. Thomas Co; 2005:762