title: Hemangiopericytoma-induced osteomalacia: tumor transplantation in nude mice causes hypophosphatemia and tumor extracts inhibit renal 25-hydroxyvitamin D 1-hydroxylase activity.
abstract: Although more than 50 patients with the tumor-induced osteomalacia syndrome, characterized by remission of unexplained osteomalacia after resection of a coexisting tumor, have been reported, the pathogenesis of this syndrome is still not clear. We investigated the cause of biopsy-confirmed osteomalacia which was resistant to treatment with 1 alpha-hydroxyvitamin D3 in a 54-yr-old man. He had severe hypophosphatemia, a high serum alkaline phosphatase level, a low plasma 1,25-dihydroxyvitamin D level, and remarkably increased urinary phosphorus excretion. A tumor, with histological characteristics of a hemangiopericytoma, was found on his left thigh. After surgical removal of this tumor, his plasma 1,25-dihydroxyvitamin D and serum phosphorus levels increased to normal levels, and his bone pain subsided. The tumor was transplanted to athymic nude mice. A nodule formed in each mouse, with histological features identical to those of the original tumor, and the tumor-bearing mice had hypophosphatemia, high serum alkaline phosphatase levels, and increased urinary phosphorus excretion. When extracts of the original tumor were added to primary cultures of renal tubular cells, renal cAMP levels did not change, but 25-hydroxyvitamin D-1 alpha-hydroxylase activity was significantly inhibited. These data indicate tumoral production of some humoral factor(s) inhibiting 25-hydroxyvitamin D-1 alpha-hydroxylase activity and phosphorus reabsorption unrelated to adenylate cyclase-cAMP production in proximal renal tubules.
authors.affiliation: Department of Medicine, Kobe University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Miyauchi
authors.forename: M
authors.initials: M
authors.lastname: Fukase
authors.forename: M
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: T
authors.initials: T
authors.lastname: Fujita
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D000242:Cyclic AMP / Q000378:metabolism; D005266:Femoral Neoplasms / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000628:therapy; D006393:Hemangiopericytoma / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010018:Osteomalacia / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D010710:Phosphates / Q000097:blood*; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*; D014020:Tissue Extracts / Q000494:pharmacology*
chemical_list: D010710:Phosphates; D014020:Tissue Extracts; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase