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  • Low bone density from defective mineralization.

  • Caused by deficiency in calcium, phosphorus, or low alkaline phosphatase.

  • Rickets: defective bone mineralization in childhood or adolescence before epiphyseal fusion.

  • Osteomalacia: defective bone mineralization in adults with fused epiphyses.

  • Painful proximal muscle weakness (especially pelvic girdle); bone pain.

  • Low serum 25-hydroxy-vitamin D (25-OHD), hypocalcemia, hypocalciuria, hypophosphatemia, secondary hyperparathyroidism.

  • Classic radiologic features may be present.


Defective mineralization of the growing skeleton in childhood causes permanent bone deformities (rickets). Defective skeletal mineralization in adults is known as osteomalacia. It is caused by inadequate calcium or phosphate mineralization of bone osteoid.


Causes of osteomalacia are listed in Table 26–11.

Table 26–11.Causes of osteomalacia.1

A. Vitamin D Deficiency

Vitamin D is predominantly synthesized in the skin during exposure to UV B light (Table 26–11). Vitamin D is also consumed in the diet from plants (ergocalciferol, D2) or animals/fish (cholecalciferol, D3). Both forms of vitamin D are converted in the liver to 25-hydroxyvitamin D (25-OHD); 25-OHD is subsequently converted in various tissues (mainly kidney) to 1,25-dihydroxyvitamin D (1,25[OH]2D), the active hormone whose production is regulated by serum calcium, phosphorus, and PTH. 1,25(OH)2D binds to cytoplasmic vitamin D receptors, increasing the absorption of dietary calcium from the intestine and increasing the reabsorption of calcium in the renal tubule, thereby reducing calcium loss in the urine. 1,25(OH)2D also stimulates bone osteoblasts to release RANKL that stimulates osteoclasts, which release calcium from bone.

Vitamin D deficiency is the most common cause of osteomalacia; its incidence is increasing throughout the world as a result of diminished exposure to sunlight caused by urbanization with use of automobile and public transportation, living at high latitudes, winter season, institutionalization, sunscreen use, or very modest dressing. About 36% of adults in the United States are deficient in vitamin D.

Other risk factors for vitamin D deficiency include the following: pregnancy, age over 65 years, obesity, dark skin, ...

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