title: Cinacalcet in the management of tumor-induced osteomalacia.
abstract: 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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Research Institute, Cedars-Sinai Medical Center and the David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Geller
authors.forename: Azarmindokht
authors.initials: A
authors.lastname: Khosravi
authors.forename: Marilyn H
authors.initials: MH
authors.lastname: Kelly
authors.forename: Mara
authors.initials: M
authors.lastname: Riminucci
authors.forename: John S
authors.initials: JS
authors.lastname: Adams
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
mesh_terms: D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002117:Calcitriol / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D000069449:Cinacalcet; D004359:Drug Therapy, Combination; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D007011:Hypoparathyroidism / Q000139:chemically induced; D017674:Hypophosphatemia / Q000188:drug therapy; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications*; D010018:Osteomalacia / Q000188:drug therapy* / Q000209:etiology; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D010758:Phosphorus / Q000097:blood / Q000378:metabolism; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: C000717427:FGF23 protein, human; D009281:Naphthalenes; D010281:Parathyroid Hormone; D010710:Phosphates; D006852:Hydrochlorothiazide; D014807:Vitamin D; D010758:Phosphorus; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D; D002117:Calcitriol; D002118:Calcium; D000069449:Cinacalcet