title: Potential effects of alendronate on fibroblast growth factor 23 levels and effective control of hypercalciuria in an adult with Jansen's metaphyseal chondrodysplasia.
abstract: BACKGROUND
  Jansen's metaphyseal chondrodysplasia (JMC) is a rare autosomal dominant disorder caused by activating mutations in the PTH 1 receptor (PTH1R; PTH/PTHrP receptor), leading to chronic hypercalcemia and hypercalciuria. Hypophosphatemia is also a hallmark of JMC, and recently, increased fibroblast growth factor 23 (FGF23) levels have been reported in this syndrome. Hypercalcemia has been associated with increased cardiovascular risk; however, cardiovascular disease has not been extensively investigated in JMC patients.
  
  
  OBJECTIVE
  The aim of the study was to describe the long-term follow-up of a JMC patient with regard to the management of hypercalciuria, the evaluation of FGF23 levels under bisphosphonate treatment, and the investigation of cardiovascular repercussion of chronic hypercalcemia.
  
  
  RESULTS
  The diagnosis of JCM was confirmed by molecular analysis (p.H223R mutation in PTH1R). The patient was followed from 5 to 27 yr of age. Asymptomatic nephrolithiasis was diagnosed at 18 yr of age, prompting pharmacological management of hypercalciuria. Treatment with alendronate reduced hypercalciuria; however, normocalciuria was only obtained with the association of thiazide diuretic. Serum FGF23 levels, measured under alendronate treatment, were repeatedly within the normal range. Subclinical cardiovascular disease was investigated when the patient was 26 yr old, after 19 yr of sustained mild hypercalcemia; carotid and vertebral artery ultrasonography was normal, as well as coronary computed tomography angiography (calcium score = 0).
  
  
  CONCLUSIONS
  The long-term follow-up of our JMC patient has provided insight on therapeutic strategies to control hypercalciuria, on the potential effects of alendronate on FGF23 levels, and on the lack of detectable cardiovascular disease at young adulthood after prolonged exposure to hypercalcemia.
authors.affiliation: Hospital das Clínicas, University of São Paulo School of Medicine, Avenue Dr. Eneas de Carvalho Aguiar, 155-PAMB, 2° andar, Bloco 6, 05403-900 São Paulo, SP, Brazil.
authors.forename: Laura
authors.initials: L
authors.lastname: Onuchic
authors.forename: Bruno
authors.initials: B
authors.lastname: Ferraz-de-Souza
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Pedro Henrique S
authors.initials: PH
authors.lastname: Correa
authors.forename: Regina M
authors.initials: RM
authors.lastname: Martin
mesh_terms: D000328:Adult; D019386:Alendronate / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D004359:Drug Therapy, Combination; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D053565:Hypercalciuria / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D010009:Osteochondrodysplasias / Q000503:physiopathology*; D012720:Severity of Illness Index; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; C000717427:FGF23 protein, human; D049993:Sodium Chloride Symporter Inhibitors; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D019386:Alendronate