Potential Effects of Alendronate on Fibroblast Growth Factor 23 Levels and Effective Control of Hypercalciuria in an Adult with Jansen's Metaphyseal Chondrodysplasia

• Published in: The journal of clinical endocrinology and metabolism Vol. 97; no. 4; pp. 1098 - 1103
• Main Authors: Onuchic, Laura, Ferraz-de-Souza, Bruno, Mendonca, Berenice B, Correa, Pedro Henrique S, Martin, Regina M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.04.2012
• Subjects: Adult; Alendronate - therapeutic use; Biological and medical sciences; Bone Density Conservation Agents - therapeutic use; Cardiovascular Diseases - etiology; Cardiovascular Diseases - prevention & control; Drug Therapy, Combination; Endocrinopathies; Feeding. Feeding behavior; Female; Fibroblast Growth Factors - blood; Fundamental and applied biological sciences. Psychology; Humans; Hypercalcemia - etiology; Hypercalcemia - physiopathology; Hypercalcemia - prevention & control; Hypercalciuria - blood; Hypercalciuria - drug therapy; Hypercalciuria - etiology; Medical sciences; Osteochondrodysplasias - physiopathology; Severity of Illness Index; Sodium Chloride Symporter Inhibitors - therapeutic use; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Human; Obesity; Antiosteoporotic; Nutrition; Diseases of the osteoarticular system; Nutrition disorder; Antiresorptive agent; Diphosphonic acid derivatives; Metabolic diseases; Bisphosphonates; Genetic disease; Alendronic acid; Metaphyseal chondrodysplasia; Hypercalciuria; Fibroblast growth factor-23; Surveillance; Adult; Osteochondrodysplasia; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2011-3082

Context: 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). Conclusion: 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.