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Abnormal bone mineralization
42%
48/113
Carbonic anhydrase deficiency
3%
3/113
Decreased volume of normal bone
12%
13/113
Increased osteoclast activity
30%
34/113
Upregulation of phosphate reabsorption
9%
10/113
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This patient who presents with bone pain and a fracture associated with poor dietary intake, decreased calcium, decreased phosphate, and increased alkaline phosphatase most likely has osteomalacia, which is caused by decreased vitamin D levels associated with abnormal bone mineralization. Vitamin D is a fat-soluble vitamin that increases the absorption of calcium and phosphate in the intestines. It can be ingested as part of the diet or synthesized in the skin upon exposure to sunlight; however, it must be hydroxylated sequentially by the liver in the 25-position and the kidney in the 1-position before it exerts its physiologic effect. Decreased vitamin D levels lead to osteomalacia in adults and rickets in children due to defective mineralization of osteoid. This will present with bone pain and fractures as well as additional findings of bowed legs and kyphosis in children. Vitamin D deficiency will have decreased calcium, decreased phosphate, and increased alkaline phosphatase levels. Incorrect Answers: Answer 2: Carbonic anhydrase deficiency is consistent with the pathogenesis of osteopetrosis; however, this disease would present in childhood with multiple long bone fractures and pancytopenia due to encroachment of bone into the medullary space. Answer 3: Decreased volume of normal bone is consistent with the pathogenesis of osteoporosis, which may also present with fragility fractures; however, serum levels of calcium, phosphate, and alkaline phosphatase would be normal in these patients since the disease is caused by decreased bone quantity with no change in quality. Answer 4: Increased osteoclast activity is consistent with the pathogenesis of Paget disease of the bone, which can also present with an elevation in alkaline phosphatase; however, this disease would also have increased head circumference, increased hand and foot size, and high output heart failure in late stages. Answer 5: Upregulation of phosphate reabsorption is consistent with the pathogenesis of osteitis fibrosa cystica, which can also present predominantly with bone pain; however, this disease would have calcium and phosphate levels that go in opposite directions rather than both decreasing. Bullet Summary: Vitamin D must be activated by hydroxylation in the kidney, and deficiency of this factor leads to osteomalacia and rickets.
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