Octreotide Therapy for Tumor-Induced Osteomalacia

Abstract

UMOR-induced osteomalacia (also known as oncogenic osteomalacia) 1 is a rare disorder characterized by phosphaturia, hypophosphatemia, and osteomalacia mimicking the clinical phenotype of either X-linked 2 or autosomal dominant 3 hereditary hypophosphatemic rickets. Tumor-induced osteomalacia develops because of tumors that are predominantly of benign mesenchymal origin 4 but that may occasionally be malignant, as was recently reported. 5 Surgical removal of the tumor relieves all symptoms. Hemangiopericytoma is the most dominant histologic entity in tumor-induced osteomalacia. 4,6 Paraneoplastic secretion by the tumor of an unknown factor or factors -termed "phosphatonins" -causing renal tubular phosphate wasting has been proposed as the pathogenic mechanism. 7 We describe an adult man who had hypophosphatemic osteomalacia for several years before an octreotide scan revealed a mesenchymal tumor in his left thigh. Moreover, subcutaneous administration of octreotide, a synthetic somatostatin analogue, abolished renal tubular phosphate wasting before subsequent surgical removal of the tumor. CASE REPORTA 50-year-old man presented with chronic pain of the spine, ribs, femurs, and tibias. The clinical examination was otherwise normal. There was no family history of metabolic bone disease.The initial evaluation in July 1997 revealed elevated urinary phosphorus excretion, low serum phosphorus levels, and elevated serum alkaline phosphatase and osteocalcin levels. The serum values for calcium, parathyroid hormone, 25-hydroxyvitamin D 3 , and calcitonin were normal; the serum value for 1,25-dihydroxy-T vitamin D 3 was inappropriately low (6.9 pg per milliliter; normal range, 35 to 80). The diagnostic evaluation at this time provided no evidence of tumor. Multiple rib fractures were identified. A bone scan with technetium-99m-labeled 2,3-dicarboxypropane-1,1diphosphonate showed a pattern of focal, late-phase enhancement in the spine and ribs; this was suggestive of metabolic bone disease. The patient was given the diagnosis of idiopathic hypophosphatemic osteomalacia with renal phosphate wasting. Continuous oral supplementation with phosphate and 1,25-dihydroxyvitamin D 3 (1.25 µg per day) was initiated. Three years after the initial diagnosis, progressive metabolic bone disease prompted another extensive evaluation. METHODS AssaysSerum, plasma, and urinary constituents were measured by standard techniques. Hormone measurements were performed with the use of commercial immunoassay kits. Assays of serum parathyroid hormone, 25-hydroxyvitamin D 3 , 1,25-dihydroxyvitamin D 3 , and calcitonin were performed with commercial kits (DPC Biermann, Bad Nauheim, Germany), as were those for osteocalcin (Diagnostic Systems Laboratories, Sinsheim, Germany) and urinary type I collagen C-telopeptides (Beckmann Coulter, Krefeld, Germany). For calculation of renal clearance of phosphate, serum and urinary concentrations of phosphorus were determined together with the excreted urinary volume during two one-hour collection periods (Table 1)....

The Phosphaturic Mesenchymal Tumor: Why is Definitive Diagnosis and Curative Surgery Often Delayed?

“…As a result of the presence of somatostatin receptors on these tumors, it has been suggested that octreotide, a synthetic somatostatin analogue, would be useful in decreasing FGF-23 secretion [20]. Although there is one case report regarding use of octreotide as mitigating therapy before definitive treatment [20], few clinicians have been successful in repeating the initial success with this technique [3,4,13,16].…”

MEPE has the properties of an osteoblastic phosphatonin and minhibin

“…MEPE expression occurs in all OHO tumors screened and is notably absent in non-phosphaturic tumors [15,71,79,81]. The exclusive osteoblast expression profile of MEPE, its temporal expression with PHEX, its marked up-regulation in HYP, its presence as a secreted protein in serum and matrix, the coordinate down-regulation of MEPE expression by PHEX and 1,25-dihydroxy vitamin-D 3 , and the overexpression and secretion by OHO tumors indicated to us that MEPE is a good candidate for an OB-PTN [2,3,15,26,29,50,71,79,81].…”

“…MEPE is a secreted RGD-matrix phosphoglycoprotein up-regulated in OHO tumors and Hyp osteoblasts. Moreover, MEPE is exclusively expressed in osteoblasts, osteocytes and odontoblasts [2,3,15,26,29,62,71,79,81]. MEPE also belongs to the short integrin-binding ligand interacting glycoprotein (SIBLING) family that all map to 4q21.1 [24,71].…”

Expectations of Response from Octreotide Therapy in Recurrent Phosphaturic Mesenchymal Tumors - Do They Reflect Reality?

“…It has been proposed that in cases in whom somatostatin receptors have been demonstrated with octreotide scintigraphy, somatostatin analogue octreotide treatment decreases hypophosphatemia and phosphate deficiency and that phosphate metabolism may be regulated by somatostatin receptors (Seufert et al, 2001). However, it was also observed that, Octreotide treatment does not yield the same results in all cases (Paglia F et al, 2002).…”