Parathyroid hormone-related protein in the aetiology of fibrous dysplasia of bone in the McCune Albright syndrome

OBJECTIVE Fibrous dysplasia, observed in bone lesions in the McCune Albrigh t syndrome (MAS), is thought to result from abnormalities in cells of the o steogenic lineage associated with over-activation of the cAMP signalling pa thway in affected cells. The aim of this study was to investigate the role of parathyroid hormone-related protein (PTHrP) in the aetiology of MAS, and to determine a possible therapeutic role for 1,25-dihydroxy vitamin D-3 (1 ,25(OH)(2)D-3). DESIGN The effects of 1,25(OH)(2)D-3 on PTHrP production and mRNA expressio n were determined in vitro. 1,25(OH)(2)D-3 therapy was administered to thre e patients with MAS. PATIENTS Clinical data from four MAS patients (MAS1, 2, 3 and 4), and in vi tro studies using bone from three MAS patients (MAS1, 2, and 3), are presen ted. MEASUREMENTS Immunoradiometric assay and low-cycle number reverse transcrip tase-linked PCR were used to determine PTHrP production and mRNA expression in vitro. Standard clinical biochemistry was recorded pre and post commenc ement of 1,25(OH)(2)D-3 treatment. RESULTS We report the elevated secretion of PTHrP, and a concomitant rise i n PTHrP mRNA expression, in cultured osteoblasts from three MAS patients. T reatment with 1,25(OH)(2)D-3 produced a dose-dependent decrease in PTHrP pr otein secretion and mRNA expression. Marked improvement in bone biochemistr y in MAS1, 2 and 3 post treatment with 1,25(OH)(2) D-3 is documented. CONCLUSIONS This study provides the first evidence suggesting that PTHrP ma y contribute to the aetiology of fibrous dysplasia in MAS. In addition, the therapeutic administration of 1,25(OH)(2)D-3 may provide clinicians with a n important new regime for symptomatic relief of bone pain and fracture in some patients with MAS.