Patients present with muscle weakness, bone pain, or fractures. Children will have rickets (bowing at the knees). Xrays disclose osteopenia, Looser's zones or wide epiphyseal plates. Bone scans may show multiple lesions, and increased activity at the ends of the ribs resembles the "rachetic rosary" seen with vitamin D deficiency.
Lab values typically include very low phosphate and 1,25-dihydroxyvitamin D, but normal 25-hydroxyvitamin D levels. There is renal phosphate loss, but renal function is otherwise normal. Amino-aciduria, renal tubular acidosis, or glucosuria indicate Fanconi's syndrome, which may resemble oncogenic osteomalacia. Calcium may be normal or slightly low. Parathyroid hormone is increased in some cases. Alkaline phosphate is elevated. Other routine biochemical tests are unremarkable.
Bone biopsies demonstrate osteomalacia.
These photomicrographs demonstrate serious osteomalacia. When measured, 40% of the bone volume was unmineralized osteoid. The osteoid is orange and the mineralized bone is green. The second view, at higher magnification and under polarized light, shows the lamellar nature of the osteoid.
It has been clear for a long time that a humoral substance caused the osteomalacia, because the bone disease resolves when the tumors are resected. Identification of the factor, however, has been very difficult, because the tumors did not grow well in culture or in animals. Recently researchers have been more successful, and the factor appears to be a phosphaturic peptide, "phosphatonin" which acts at the level of the proximal renal tubule, inhibiting sodium-dependent phosphate transport. FGF-23 (one of the fibroblastic growth factors) is elevated in oncogenic osteomalacia, and it increases in normal persons when given a phosphate load, so this is probably the same as phosphatonin. (reported at the 2002 ASBMR meetings) This may be related to the abnormalities seen in patients with x-linked hypophosphatemic rickets, who have a mutation in the PEX gene. The PEX gene-product inhibits phosphatonin, so a defective PEX gene-product will fail to inhibit phosphatonin, resulting in phosphate wasting. The phosphaturia in both cases in associated with inhibition of 1-alpha-hydroxylase, so 1,25-dihydroxy-vitamin D is low. In oncogenic osteomalacia it is very low, and in x-linked hypophosphatemic rickets it is lower than it should be for the level of phosphate.
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