title: Outcome of Long-Term Bisphosphonate Therapy in McCune-Albright Syndrome and Polyostotic Fibrous Dysplasia.
abstract: McCune-Albright syndrome (MAS) is a rare bone disorder characterized by fibrous dysplasia (FD), endocrinopathies, and café-au-lait patches. FD patients have been shown to respond favorably to treatment with bisphosphonates, but data are scarce in the more severe polyostotic form (PFD), including MAS, and factors determining treatment outcome are not known, particularly in the long-term. We evaluated the biochemical (bone turnover markers [BTMs]) and clinical (pain reduction) outcome of bisphosphonate therapy in 11 patients with MAS and 30 patients with PFD: median duration of treatment 6 years (range, 2 to 25 years). Prognostic factors for treatment outcome were identified in both groups. Patients with MAS were younger at diagnosis (p = 0.001), all had precocious puberty, and four (36%) had additional growth hormone (GH) excess associated with severe craniofacial FD. Extent of skeletal disease was more severe in MAS compared to PFD. MAS patients had higher serum alkaline phosphatase (ALP) concentrations (p = 0.005), higher skeletal burden scores (p < 0.001), and more fractures (p = 0.021). MAS patients had also higher levels of FGF-23 (p = 0.008) and higher prevalence of hypophosphatemia (p = 0.013). Twenty-four of 30 PFD patients (80%) demonstrated a complete clinical and biochemical response within a year of starting treatment (p = 0.015), compared to only four of 11 MAS patients (36%). There were no nonresponders. In the whole group, FGF-23, total ALP, P1NP, and CTX positively correlated with skeletal burden scores (all p ≤ 0.001), which was the only significant risk factor for an incomplete response to bisphosphonate therapy (p < 0.01). Our data suggest a beneficial and safe outcome of long-term bisphosphonate therapy in the majority of patients with PFD, although response to therapy was limited by the higher skeletal disease burden in MAS patients. In the PFD/MAS population studied, the only identified prognostic factor that influenced the outcome of bisphosphonate therapy was a high skeletal burden score. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.|Department of Orthopaedic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Bas Cj
authors.initials: BC
authors.lastname: Majoor
authors.affiliation: Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.|Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Appelman-Dijkstra
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.|Mathematical Institute, Leiden University, Leiden, The Netherlands.
authors.forename: Martha
authors.initials: M
authors.lastname: Fiocco
authors.affiliation: Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.|Department of Orthopaedic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Michiel Aj
authors.initials: MA
authors.lastname: van de Sande
authors.affiliation: Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.|Department of Orthopaedic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Pd Sander
authors.initials: PS
authors.lastname: Dijkstra
authors.affiliation: Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.|Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Neveen At
authors.initials: NA
authors.lastname: Hamdy
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005359:Fibrous Dysplasia, Polyostotic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004164:Diphosphonates; C000717427:FGF23 protein, human; D000089703:Fibroblast Growth Factor-23; D000469:Alkaline Phosphatase
keywords: ANTIRESORPTIVES; BIOCHEMICAL MARKERS OF BONE TURNOVER; DISEASES AND DISORDERS OF/RELATED TO BONE, OTHER; FIBROUS DYSPLASIA; GENERAL POPULATION STUDIES; GH/IGF-1