Oncogenic Osteomalacia

ABSTRACT

Oncogenic osteomalacia is a rare paraneoplastic syndrome caused by bone and soft tissue tumors. The characteristic clinical, metabolic, and imaging findings are reviewed, as is the radiologist's role in evaluation and diagnosis. New insight into the pathophysiology of oncogenic osteomalacia is also presented.

KEYWORD

Oncogenic osteomalacia - metabolic bone disease - matrix extracellular phosphoglycoprotein - tumor imaging

REFERENCES

• 1 Prader V A, Illig R, Vehlinger E, Stalder G. Rachitis, Infole, Knochen tumors.  Helv Pediatr Acta . 1959;  14 554-565
• 2 Dorfman H D, Czerniak B. Bone Tumors.  St. Louis: Mosby 1998: 1111-1119
• 3 Camus J P, Crouzet J, Prier A. Osteomalacies hypophosphoremiques guéries par l'ablation de tumeurs benignes du tisu conjonctif.  Ann Med Intern (Paris) . 1980;  131 422-426
• 4 Furuya K, Isobe Y, Morita M. Hypertrophic osteoarthropathy and hypophosphatemic osteomalacia associated with tumor.  Gan To Kajaku Ryoho . 1986;  13 2056-2064
• 5 Gitelis S, Ryan W J, Rosenberg A G, Templeton A C. Adult-onset hypophosphatemic osteomalacia secondary to vascular tumors of bone and soft tissue.  J Bone Joint Surg Am . 1986;  68 134-138
• 6 McClure J, Smith P S. Oncogenic osteomalacia.  J Clin Pathol . 1987;  40 446-453
• 7 Renton P, Shaw D G. Hypophosphatemic osteomalacia secondary to vascular tumors of bone and soft tissue.  Skeletal Radiol . 1976;  1 21-24
• 8 Seshadri M S, Cornish C J, Mason R S, Posen S. Parathyroid hormone-like bioactivity in tumors from patients with oncogenic osteomalacia.  Clin Endocrinol . 1985;  23 689-697
• 9 Weidner N, Santa Cruz D. Phosphaturic mesenchymal tumors.  Cancer . 1987;  59 1442-1454
• 10 Pollack J A, Schiller A L, Crawford J D. Rickets and myopathy cured by removal of a non-ossifying fibroma of bone.  Pediatrics . 1973;  52 364-372
• 11 Martini A, Notarangeleno L D, Barberis L. Acquired vitamin-D resistant rickets caused by prolonged latency in appearance of bone tumor.  Am J Dis Child . 1983;  137 1025-1026
• 12 Sparagana M. Tumor-induced osteomalacia: long-term follow up of two patients cured by removal of their tumors.  J Surg Oncol . 1987;  36 198-205
• 13 Nomura G, Koshino Y, Morimoto H. Vitamin D resistant hypophosphatemic osteomalacia associated with osteosarcoma of the mandible: report of a case.  Jpn J Med . 1981;  21 35-39
• 14 Park Y K, Unni K K, Beabout J W, Hodgson S F. Oncogenic osteomalacia: a clinicopathologic study of 17 bone lesions.  J Korean Med Sci . 1994;  9 289-298
• 15 Wyman A L, Paratinas F J, Daly J R. Hypophosphatemic osteomalacia associated with a malignant tumor of the tibia: report of a case.  J Clin Pathol . 1997;  30 328-335
• 16 Sparagana M. Tumor-induced osteomalacia: long-term follow up of two patients cured by removal of their tumors.  J Surg Oncol . 1987;  36 198-205
• 17 Castleman B, Mc Neely U B. Case records of the Massachusetts General Hospital.  N Engl J Med . 1965;  273 494-504
• 18 Hasegawa T, Shimoda T, Yokoyama R. Intracortical osteoblastic osteosarcoma with oncogenic rickets.  Skeletal Radiol . 1999;  28 41-45
• 19 Clunie F PR, Fox P E, Stamp T CB. Four cases of acquired hypophosphatemic ("oncogenic") osteomalacia: problems of diagnosis, treatment and long-term management.  Rheumatology . 2000;  39 1415-1421
• 20 Seufert J, Ebert K, Muller J, Eulert. Brief report: octreotide therapy for tumor-induced osteomalacia.  N Engl J Med . 2001;  345 1883-1888
• 21 Ohashi K, Ohnishi T, Ishikawa T. Oncogenic osteomalacia presenting as bilateral stress fractures of the tibia.  Skeletal Radiol . 1999;  28 46-48
• 22 Avila N A, Skarulis M, Rubino D M, Doppman J L. Oncogenic osteomalacia: lesion detection by MR skeletal survey.  AJR Am J Roentgenol . 1996;  167 343-345
• 23 Jan de Beur M S, Streeten E A, Civelek A C. Localisation of mesenchymal tumours by somatostatin receptor imaging [research letter].  Lancet . 2002;  359 761-763
• 24 Sundaram M, McCarthy E F. Oncogenic osteomalacia.  Skeletal Radiol . 2000;  29 117-124
• 25 Drezner M K. Tumor-induced rickets and ostomalacia. In: Favus MJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism New York: Raven Press 1996: 319-325
• 26 Aschinberg L C, Solomon L M, Zeis P M, Justice P, Rosenthal I M. Vitamin D-resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions.  J Pediatr . 1977;  91 56-60
• 27 Lau K, Stom M C, Goldberg M. Evidence for a humoral phosphaturic factor in oncogenic hypophosphatemic osteomalacia (Abst).  Clin Res . 1979;  27 421
• 28 Popvtzer M M. Tumor-induced hypophosphatemic osteomalacia (TUO): evidence for a phosphaturic cyclic AMP-independent action of tumor extract (Abst).  Clin Res . 1981;  29 418
• 29 Miyauchi A, Fukase M, Tsutsumi M, Fujita T. Hemangiopericytoma-induced osteomalacia: tumor transplantation in nude mice causes hypophosphatemia and tumor extracts inhibit renal 25-hydroxyvitamin D 1-hydroxylase activity.  J Clin Endocrinol Metab . 1988;  67 46-53
• 30 Cai Q, Hodgson S F, Kao P C. Brief report: inhibition of renal phosphate transport by a tumor product in a patient with oncogenic osteomalacia.  N Engl J Med . 1994;  330 1645-1649
• 31 Econs M J, Drezner M K. Tumor-induced osteomalacia: unveiling a new hormone [editorial comment].  N Engl J Med . 1994;  330 1679-1681
• 32 Shimada T, Mizutani S, Muto T. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia.  Proc Natl Acad Sci USA . 2001;  98 6500-6505
• 33 John M R, Wickert H, Zaar K. A case of neuroendocrine oncogenic osteomalacia associated with a PHEX and fibroblast growth factor-23 expressing sinusidal malignant schwannoma.  Bone . 2001;  29 393-402
• 34 Rowe P SN, de Zoysa A P, Dong R. MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia.  Genomics . 2000;  67 54-68
• 35 Argiro L, Desbarats M, Glorieux F H, Ecarot B. MEPE, the gene encoding a tumor-secreted protein in oncogenic hypophosphatemic osteomalacia, is expressed in bone.  Genomics . 2001;  74 342-351
• 36 Francis F, Henning S, Korn B. Positional cloning of PEX: a phosphate regulating gene with homologies to endopeptidases is detected in patients with X-linked hypophosphatemic rickets.  Nat Genet . 1995;  11 130-136