Tumor-Induced Vitamin D-Resistant Hypophosphatemic Osteomalacia Associated with Proximal Renal Tubular Dysfunction and 1,25-Dihydroxyvitamin D Deficiency

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Abstract
Tumor-induced osteomalacia is recognized as vitamin D-resistant hypophosphatemic osteomalacia that heals after resection of a coexisting mesenchymal tumor in either bone or soft tissue. We have investigated the underlying causal mechanism for osteomalacia in a 27-yr-old woman who presented witha several-year history of progressive muscle weakness and pain. Bone roentgenograms showed Looser's zones, and blood chemistry revealed severe hypophosphatemia (1.3 mg/dl) and a high alkaline phosphatase level (31 King-Armstrong units). Bone biopsy confirmed the diagnosis of osteomalacia. Increased urinary phosphorus excretion was shown by decreased tubular resorption of phosphate (75.8%) and a low (0.9 mg/dl) calculated renal phosphorus threshold. Renal glucosuria (271 ± 60 mg/day) and generalized aminoaciduria (2,063 mg/day) also were discovered, indicating impaired proximal renal tubular reabsorptive function. Chronic renal insufficiency, systemic acidosis, malabsorption, and hypophosphatasia were excluded as causes of osteomalacia. The serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] was very low (¼4 pg/ml), although the 25OHD level was normal (52 ng/ml). However, restoration of the 1,25(OH)2D level by oral administration of lαOHD3 produced only partial correction of hypophosphatemia and hyperphosphaturia. Resection of a tumor in the left tibia, which histologically resembled benign osteoblastoma, resulted in prompt and complete normalization of biochemical abnormalities and serum 1,25(OH)2D level and radiological healing of osteomalacia. We suggest that tumor-induced proximal tubular impairment caused hypophosphatemic osteomalacia via excessive urinary loss of phosphorus and 1,25(OH)2D deficiency, possibly due to defective formation.