De Filippo, G.

Mossetti, G.

Rendina, D.

Sorrentino, M.

Strazzullo, P.

Zampa, G.

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RELATIONSHIP BETWEEN 3’VDR HAPLOTYPES AND ACQUIRED RESISTANCETO CLODRONATE TREATMENT IN PATIENTS WITH PAGET’S DISEASE OF BONED. Rendina1, G. De Filippo2, M. Sorrentino1, G. Zampa1, P. Strazzullo1, G. Mossetti11 Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Naples, Italy2 Unit of Paediatric Endocrinology, A.O.R.N. “G. Rummo” Benevento, Benevento, Italy The 1,25(OH)2D3/vitamin D receptor (VDR) system plays a key role in the pathogenesis of metabolicbone diseases, including Paget’s bone disease (PDB). In these diseases, VDR allelic variants significant-ly influence the effectiveness of antiresorptive treatments. This retrospective case-control study was per-formed to evaluate the pharmacological response to clodronate treatment according to Bsm1, Taq1 andFok1 VDR polymorphisms in 84 (M:F 48:36; mean age 60.2±9.1 years) patients with poliostotic PDB fromCampania, Southern Italy. All patients were treated from diagnosis for several cycles with intravenous clodronate infusion (1500mg/cycle). The acquired resistance to clodronate treatment was defined as the failure of the total alkalinephosphatase serum levels to be suppressed to at least 50% of the patient’s previous highest levels duringa subsequent treatment course with the same compound (clodronate), which produced a >50% responseafter the first exposure. Considering the linkage disequilibrium between BsmI and TaqI VDR sites, PDBpatients were classified as homozigous (BBtt and bbTT) or heterozygous in relation to BsmI-TaqI cluster. The acquired resistance to clodronate occurs in 31 PDB patients (36.9%, M:F 17:14; mean age 58.2±8.9years; i.e. resistant). The prevalence of bbTT haplotypes in PDB resistant patients is higher compared tothose observed in PDB patients without clodronate acquired resistance (i.e. responders) (F 8.737; p0.013). The relative risk to develop acquired resistance to clodronate treatment in homozigous bbTT PDBpatients is 7.00 (95% C.I. 1.57-31.18). Additional analysis of FokI alleles was not more informative. Nosignificant differences in clinical characteristics at diagnosis, time of observation, treatment courses andtotal dose of clodronate administration were found among resistant and responder PDB patients. Our results confirm that the different VDR genetic variants significantly influence the action mechanism ofbisphosphonate and suggest a link between 3’VDR allelic variants and the occurrence of acquired resis-tance to clodronate treatment in patients with poliostotic PDB. 238 Clinical Cases in Mineral and Bone Metabolism 2005; 2(3): 185-252BSTR CT (V Congresso CCMBM)  18/11/2005  15.59  Pagina 238FOR REVIEW ONLY© CIC EDIZIONI INTERNAZIONALI

Relationship between 3'VDR haplotypes and acquired resistance to clodronate treatment in patientd with paget's disease of bone

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Relationship between 3'VDR haplotypes and acquired resistance to clodronate treatment in patientd with paget's disease of bone

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