Oncogenic osteomalacia: Problems in diagnosis and long-term management

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Abstract

Oncogenic osteomalacia is a rare association between mesenchymal tumors and hypophosphatemic rickets. It is more of a biochemical entity than a clinical one. The pathophysiology of the tumor is not clear. However, it has been seen that the clinical and biochemical parameters become normal if the lesion responsible for producing the osteomalacia is excised. For a clinical diagnosis a high index of suspicion is necessary. We present three such cases where in one the oncogenic osteomalacia reversed while in rest it did not. We present this case report to sensitize about the entity.

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Most cited references 18

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Tumor-induced osteomalacia and the regulation of phosphate homeostasis.

R. Kumar (2000)

Tumor-induced osteomalacia (TIO) is a rare and unique syndrome characterized by hypophosphatemia, excessive urinary phosphate excretion, reduced 1,25-dihydroxyvitamin D concentrations, and osteomalacia. Removal of the tumor is associated with a cure of the lesion. Several laboratories have now shown that conditioned medium derived from cultures of such tumors contain a small, heat-sensitive substance ("phosphatonin") of <25,000 daltons that specifically inhibits sodium-dependent phosphate transport in cultured renal proximal tubular epithelia. This substance does not increase cyclic adenosine monophosphate (cAMP) formation in tubular epithelial cells and does not increase cAMP excretion in urine. A substance with similar properties is present in the circulation of patients on hemodialysis. A syndrome with a remarkably similar biochemical phenotype, namely, X-linked hypophosphatemic rickets (XLH), also has a circulating factor with properties similar, if not identical, to those of the tumor-derived factor, "phosphatonin." The molecular defect in XLH has been shown to be due to a mutant endopeptidase, PHEX, whose substrate might be "phosphatonin." Hypophosphatemia and other biochemical abnormalities in TIO are due to excessive production of "phosphatonin" with normal PHEX function, whereas the biochemical abnormalities in XLH are caused by a mutant PHEX enzyme that fails to process "phosphatonin."

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Fibroblast growth factor 7: an inhibitor of phosphate transport derived from oncogenic osteomalacia-causing tumors.

John Sterpka, Karl L Insogna, B Ellis … (2005)

Oncogenic osteomalacia (OO), a tumor-associated phosphate-wasting syndrome, provides an opportunity to identify regulators of renal phosphate homeostasis. We established cultures from OO-associated tumors. Conditioned medium from these cultures inhibited phosphate uptake in renal tubular epithelial cells. We then compared RNA from tumor-derived cultures expressing inhibitory activity with RNA from tumor-derived cultures in which inhibitory activity was not evident and identified candidate mRNAs specifically expressed by cultures inhibiting renal phosphate transport. Testing of identified candidates revealed that one protein, fibroblast growth factor 7 (FGF7), was a potent and direct inhibitor of phosphate uptake in vitro. A neutralizing monoclonal antibody to FGF7 reversed FGF7-dependent phosphate transport inhibition and inhibitory activity in conditioned medium from tumor cell cultures. Immunoassay revealed abundant FGF7 in inhibitory conditioned medium and minimal amounts in nonconditioned medium or conditioned medium with no phosphate transport inhibitory activity. Furthermore, only small amounts of FGF23 were present in inhibitory conditioned medium, comparable to concentrations found in conditioned medium with no phosphate transport inhibitory activity. Thus, FGF7 was specifically identified when selecting for in vitro phosphate transport inhibitory activity of tumor-derived cultures and was confirmed as a potent inhibitor of phosphate transport. Finally, FGF7 message was confirmed in PCR products of mRNA extracted from fragments of each tumor. Members of the FGF family (other than FGF23) are expressed by OO-associated tumors and may play a role in mediating this syndrome.

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Vitamin D-resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions.

Lorenzo Aschinberg, Lawrence Solomon, Petros Zeis … (1977)

A 5-year-old boy was found to have severe rickets in association with hyperpigmented, linear, verrucous, epidermal tumors, typical of the epidermal nevus syndrome. Normocalcemia (9.6 mg/dl), hypophosphatemia (2.0 mg/dl), elevated serum alkaline phosphatase concentration (313 IU), decreased renal tubular reabsorption of phosphorus (35%), radiologic evidence of rickets, and lack of response to usual therapeutic doses of vitamin D suggested hypophosphatemic vitamin D-resistant rickets. Therapy with vitamin D in doses to 750,000 IU and oral phosphate, 2.0 gm/day, failed to induce healing of the rickets. A subtotal parathyroidectomy performed when the patient was 9 years old was also without effect. When he was 12 years old several fibroangiomas on the face and left lower limb were excised. Within three months all biochemical abnormalities resolved and radiologic evidence of healing was observed. A portion of excised tissue was homogenized and injection of the supernate into a 6-week-old puppy induced excessive phosphaturia. The data suggest that the rickets was induced by a phosphaturic substance extractable from the tumors.

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Journal

Journal ID (nlm-ta): Indian J Orthop

Journal ID (publisher-id): IJOrtho

Title: Indian Journal of Orthopaedics

Publisher: Medknow Publications (India )

ISSN (Print): 0019-5413

ISSN (Electronic): 1998-3727

Publication date (Print): Oct-Dec 2010

Volume: 44

Issue: 4

Pages: 453-457

Affiliations

Department of Orthopedics, UCMS and GTB Hospital, Delhi, India

Author notes

Address for correspondence: Dr. Ajay Pal Singh, Residential Complex, D-13. UCMS and GTB Hospital, Dilshad Garden, New Delhi, India. E-mail: docajaypal@ 123456gmail.com

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Publisher ID: IJOrtho-44-453

DOI: 10.4103/0019-5413.69320

PMC ID: 2947736

PubMed ID: 20924490

SO-VID: 31a93eff-875c-413f-80f7-58dfe7e86921

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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Oncogenic osteomalacia: Problems in diagnosis and long-term management

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Most cited references 18

Tumor-induced osteomalacia and the regulation of phosphate homeostasis.

Fibroblast growth factor 7: an inhibitor of phosphate transport derived from oncogenic osteomalacia-causing tumors.

Vitamin D-resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions.

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