Cinacalcet in the Management of Tumor-Induced Osteomalacia

Clinical Research Institute, Cedars-Sinai Medical Center and the David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Journal of Bone and Mineral Research (Impact Factor: 6.83). 07/2007; 22(6):931-7. DOI: 10.1359/jbmr.070304
Source: PubMed


Both FGF-23 and PTH inhibit renal phosphate reabsorption. We treated two patients with TIO and FGF-23-mediated hypophosphatemia with cinacalcet to test the hypothesis that medicinally induced hypoparathyroidism would decrease renal phosphate wasting. Cinacalcet treatment resulted in increased renal phosphate reabsorption, allowed for a decrease in phosphate supplementation, and showed evidence of bone healing in one of the two patients.
Tumor-induced osteomalacia (TIO) is a rare, acquired disease of renal phosphate wasting, which results in hypophosphatemia and osteomalacia. It is caused by mesenchymal tumors that produce the phosphate and vitamin D-regulating hormone, fibroblast growth factor (FGF)-23. Removal of the tumor is curative, but the tumors are often difficult to locate. Medical treatment involves high doses of oral phosphate and calcitriol, but the phosphate is often poorly tolerated and leads to diarrhea. Because PTH also promotes phosphaturia, and patients with hypoparathyroidism are hyperphosphatemic in the setting of elevated serum FGF-23, we postulated that the calcium-sensing receptor agonist, cinacalcet, which can induce hypoparathyroidism, would be an effective adjuvant in the treatment of TIO.
Two subjects with presumed TIO in whom the tumor was not located after extensive testing and who did not tolerate medical therapy with phosphorus and calcitriol were treated with cinacalcet.
Neither treatment with phosphorus nor combined treatment with phosphorus and calcitriol had an effect on serum FGF-23 levels. Treatment with cinacalcet resulted in increased renal phosphate reabsorption and serum phosphorus and allowed for a decrease in phosphate supplementation to a dose that was tolerated. On this regimen, one patient showed significant bone healing as shown by resolution of activity on bone scan and lack of osteomalacia as assessed by histomorphometry.
These data show that medically induced hypoparathyroidism with cinacalcet is a therapeutic option for disorders of FGF-23-mediated hypophosphatemia and that, in the absence of PTH, the phosphaturic effect of FGF-23 is decreased.

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    • "Following the reduction of plasma PTH and hence reduced renal phosphate loss, an increase in plasma phosphate may be expected. In a study including two patients with FGF-23 mediated tumor induced osteomalacia, adjuvant therapy with cinacalcet led to increased plasma phosphate levels and allowed a substantial reduction of calcitriol and phosphate supplements [17]. A similar phosphate-saving effect of cinacalcet has been suggested in patients with XLH [14]. "
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    ABSTRACT: Hypophosphatemic rickets (HR) is a rare inherited disorder characterized by a classic rickets phenotype with low plasma phosphate levels and resistance to treatment with vitamin D. Development of secondary hyperparathyroidism (SHPT) as a direct consequence of treatment is a frequent complication and a major clinical challenge, as this may increase risk of further comorbidity. Cinacalcet, a calcimimetic agent that reduces the secretion of PTH from the parathyroid glands, has been suggested as adjuvant treatment to SHPT in patients with HR. However, only two papers have previously been published and no data are available on effects of treatment for more than six months. We now report a case of 3-year treatment with cinacalcet in a patient with HR complicated by SHPT. A 53-year-old woman with genetically confirmed X-linked dominant hypophosphatemic rickets developed SHPT after 25 years of conventional treatment with alfacalcidol and phosphate supplements. Cinacalcet was added to her treatment, causing a sustained normalization of PTH. Ionized calcium decreased, requiring reduction of cinacalcet, though asymptomatical. Level of phosphate was unchanged, but alkaline phosphatase increased in response to treatment. Cinacalcet appeared to be efficient, safe, and well tolerated. We recommend close control of plasma calcium to avoid hypocalcemia.
    Case Reports in Endocrinology 02/2014; 2014:479641. DOI:10.1155/2014/479641
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    • "Cinacalcet is another therapy proposed for TIO. Cinacalcet inhibits parathyroid hormone secretion, and parathormone increases the renal excretion of phosphate [13]. "
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    ABSTRACT: We report the case of a patient with severe muscular and articular tenderness that caused almost complete immobility. This subject had severe hypophosphatemia due to hyperphosphaturia. Fibroblast growth factor 23 (FGF-23) was abnormally high and the diagnostic of tumor-induced osteomalacia was made. Despite multiple tests, the tumor was not localized. In this report, we discuss different possible investigations to localize the tumor. Lastly, we review the potential therapy available when tumor is not found and can thus not be excised.
    Clinical biochemistry 08/2011; 44(14-15):1264-6. DOI:10.1016/j.clinbiochem.2011.07.013 · 2.28 Impact Factor
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    • "Gupta et al. (2004) found that both FGF23 and serum phosphorus were high in the blood of patients with hypoparathyroidism, indicating that in the absence of PTH, FGF23 was unable to adequately lower blood phosphorus level. This led to the notion that medically induced hypoparathyroidism may be a potential treatment for TIO (Geller et al. 2007). "
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    ABSTRACT: Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed.
    Endocrine Related Cancer 04/2011; 18(3):R53-77. DOI:10.1530/ERC-11-0006 · 4.81 Impact Factor
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