1. Signs and symptoms

2. Cause

3. Pathogenesis

4. Diagnosis
    Differential diagnosis 

5. Treatment

6. Popular culture

7. References

8. Further reading

9. External links

Oncogenic osteomalacia also known as oncogenic hypophosphatemic osteomalacia, is an uncommon disorder resulting in increased renal phosphate excretion, hypophosphatemia and osteomalacia. It may be caused by a phosphaturic mesenchymal tumor.

Signs and symptoms

Adult patients have worsening myalgias, bone pains and fatigue which are followed by recurrent fractures. Children present with difficulty in walking, stunted growth and deformities of the skeleton (features of rickets).^[1]

Cause

Tumor-induced osteomalacia is usually referred to as a paraneoplastic phenomenon, however, the tumors are usually benign and the symptomatology is due to osteomalacia or rickets.^[2] A benign mesenchymal or mixed connective tissue tumor (usually phosphaturic mesenchymal tumor ^[3] and hemangiopericytoma) are the most common associated tumors.^[4] Association with mesenchymal malignant tumors, such as osteosarcoma and fibrosarcoma, has also been reported.^[4]

Locating the tumor can prove to be difficult and may require whole body MRI. Some of the tumors express somatostatin receptors and may be located by octreotide scanning.

A phosphaturic mesenchymal tumor is an extremely rare benign neoplasm of soft tissue and bone that inappropriately produces fibroblast growth factor 23. This tumor may cause tumor-induced osteomalacia, a paraneoplastic syndrome, by the secretion of FGF23, which has phosphaturic activity (by inhibition of renal tubular reabsorption of phosphate and renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D). The paraneoplastic effects can be debilitating and are only reversed on discovery and surgical resection of the tumor.^[4]

Pathogenesis

FGF23 (fibroblast growth factor 23) inhibits phosphate transport in the renal tubule and reduces calcitriol production by the kidney. Tumor production of FGF23,^[5] Secreted frizzled-related protein 4 ^[6] and matrix extracellular phosphoglycoprotein (MEPE)^[7] have all been identified as possible causative agents for the hypophosphatemia.

Diagnosis

Biochemical studies reveal hypophosphatemia (low blood phosphate), elevated alkaline phosphatase and low serum 1, 25 dihydroxyvitamin D levels. Routine laboratory tests do not include serum phosphate levels and this can result in considerable delay in diagnosis. Even when low phosphate is measured, its significance is often overlooked. The next most appropriate test is measurement of urine phosphate levels. If there is inappropriately high urine phosphate (phosphaturia) in the setting of low serum phosphate (hypophosphatemia), there should be a high suspicion for tumor-induced osteomalacia. FGF23 (see below) can be measured to confirm the diagnosis but this test is not widely available.

Once hypophosphatemia and phosphaturia have been identified, a search for the causative tumor should begin. These are small and difficult to define. Gallium-68 DOTA-Octreotate (DOTA-TATE) positron emission tomography (PET) scanning is the best way to locate these tumors.^[8] If this scan is not available, other options include Indium-111 Octreotide (Octreoscan) SPECT/CT, whole body CT or MRI imaging.

Differential diagnosis

Serum chemistries are identical in tumor-induced osteomalacia, X-linked hypophosphatemic rickets (XHR) and autosomal dominant hypophosphatemic rickets (ADHR). A negative family history can be useful in distinguishing tumor induced osteomalacia from XHR and ADHR. If necessary, genetic testing for PHEX (phosphate regulating gene with homologies to endopepetidase on the X-chromosome) can be used to conclusively diagnose XHR and testing for the FGF-23 gene will identify patients with ADHR.

Treatment

Resection of the tumor is the ideal treatment and results in correction of hypophosphatemia (and low calcitriol levels) within hours of resection. Resolution of skeletal abnormalities may take many months.

If the tumor cannot be located, treatment with calcitriol (1-3 µg/day) and phosphorus (1-4 g/day in divided doses) is instituted. Tumors which secrete somatostatin receptors may respond to treatment with octreotide. If hypophosphatemia persists despite calcitriol and phosphate supplementation, administration of cinacalcet has been shown to be useful.^[9]

Popular culture

In season 2 of the USA Network series Royal Pains, Reshma Shetty (as Divya Katdare) diagnoses a storm chaser (Jamie Ray Newman) with recurring fractures to have tumor-induced osteomalacia.

References

Further reading

• {{cite journal |last1 = Chong |first1 = WH |last2 = Molinolo |first2 = AA |last3 = Chen |first3 = CC |last4 = Collins |first4 = MT |date = Jun 2011 |title = Tumor-induced osteomalacia |journal = Endocr Relat Cancer |volume = 18 |issue = 3 |pages = R53–77 |pmid = 21490240 |doi=10.1530/ERC-11-0006 |pmc=3433741}}
• {{cite journal |last1=Wasserman |first1=JK |last2=Purgina |first2=B |last3=Lai |first3=CK |last4=Gravel |first4=D |last5=Mahaffey |first5=A |last6=Bell |first6=D |last7=Chiosea |first7=SI |title=Phosphaturic Mesenchymal Tumor Involving the Head and Neck: A Report of Five Cases with FGFR1 Fluorescence In Situ Hybridization Analysis|journal=Head and Neck Pathology |volume=10 |issue=3 |pages=279–85 |date=12 January 2016 |pmid=26759148 |pmc=4972751 |doi=10.1007/s12105-015-0678-1}}

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