Osteomalacia Due to 1α,25-Dihydroxycholecalciferol Deficiency

Abstract

A B S T R A C T Oncogenic osteomalacia is a syndrome in which unexplained osteomalacia remits after resection of a coexisting mesenchymal tumor. We have investigated the mechanism by which a giant cell tumor of bone caused biopsy-proved osteomalacia in a 42-yrold woman. The biochemical abnormalities were: hypophosphatemia; decreased renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate; negative calcium and phosphorus balance; hyperaminoaciduria; and subnormal calcemic response to exogenously administered parathyroid hormone. Malabsorption, hypophosphatasia, fluorosis, and acidosis were excluded as causes of the osteomalacia. Serum 25-hydroxycholecalciferol was normal (27+1 ng/ml). However, the serum concentration of la,25-dihydroxycholecalciferol was low (1.6±0.1 ng/100 ml). Oral administration of physiological amounts of la,25-dihydroxycholecalciferol resulted in resolution of the biochemical abnormalities ofthe syndrome and healing of the bone pathology. We suggest that tumor-induced inhibition of la,25-dihydroxycholecalciferol synthesis caused the osteomalacia. The causal role of the tumor was proved by demonstrating that resection was accompanied by roentgenographic evidence of bone healing and maintenance of normal serum phosphorus; renal tubular maximum for the reabsorption of phosphate; calcium and phosphorus balance; aminoaciduria; and calcemic response to exogenous parathyroid hormone.

Tumor producing fibroblast growth factor 23 localized by two-staged venous sampling

“…In 1977, Drezner & Feinglos recognized impaired 1a-hydroxylation as a characteristic biochemical abnormality of the syndrome, which was later confirmed by Sweet et al (17,18). In 2001, Shimada et al identified FGF-23 as the causative humoral factor of TIO (19).…”

Altered activity of the nucleotide regulatory site in the parathyroid hormone-sensitive adenylate cyclase from the renal cortex of a patient with pseudohypoparathyroidism.

“…As illustrated in the representative experiment shown in Fig. 1, PTH stimulation resulted in a significant increase of adenylate cyclase activity at a concentration of 10 ug/ml, and the response was a linear function of the hormone concentration from [10][11][12][13][14][15][16][17][18][19][20] ,ug/ml in the preparations from both the PsH and Abnormal Adenylate Cyclase Activity in Pseudohypoparathyroidismcontrol kidneys. Furthermore, the magnitude of the response was not significantly different at each concentration of PTH employed.…”

“…Urine specimens were stored at -20°C before analysis of phosphorus (10), creatinine (11), and cyclic AMP (12). The tubular maximum of phosphate reabsorption normalized to glomerular filtration was calculated by the method of Bijvoet (13) as previously described (14). Serum PTH was measured at the Mayo Medical Laboratories, Rochester, Minn., using a carboxy terminal specific assay employing GP1M antibody (15) (normal <40 Al eq/ml).…”

Evaluation of a Role for 1,25-Dihydroxyvitamin D3 in the Pathogenesis and Treatment of X-linked Hypophosphatemic Rickets and Osteomalacia

“…Carboxyterminal-specific assays were purchased from the Mayo Medical Laboratory (Rochester, Minn.) and The Upjohn Laboratory (Kalamazoo, Mich.); normals were <40 ul eq/ml (18) and <150-375 pg eq/ml (19), respectively. An aminoterminal-specific assay (normal < 0.125 ng/ml) employing a guinea pig antibody raised against the synthetic (1-34) aminoterminal peptide of human PTH was performed in the Duke University Laboratories (20,21) and Dr. Leonard Deftos (University of Califomia, La Jolla, Calif.) measured PTH (normal < 300 pg/ml) by a predominantly carboxy-terminal immunoassay employing previously published methods (22 (29). For these studies serial 2-h urine collections on selected mornings were preceded by a water load of 20 ml/kg body wt.…”