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Calcified Tissue International
Erschienen in: Calcified Tissue International 6/2008

01.12.2008

Vitamin D Receptor Gene Polymorphisms Predict Acquired Resistance to Clodronate Treatment in Patients with Paget’s Disease of Bone

verfasst von: Giuseppe Mossetti, Luigi Gennari, Domenico Rendina, Gianpaolo De Filippo, Daniela Merlotti, Vincenzo De Paola, Pina Fusco, Teresa Esposito, Fernando Gianfrancesco, Giuseppe Martini, Ranuccio Nuti, Pasquale Strazzullo

Erschienen in: Calcified Tissue International | Ausgabe 6/2008

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Abstract

Bisphosphonates are first-choice drugs for treatment of Paget’s disease of bone (PDB); nevertheless, acquired resistance to bisphosphonate therapy has been described in PDB patients. The 1,25(OH)2D3/vitamin D receptor (VDR) system influences the effectiveness of antiresorptive treatments in metabolic bone disorders. This study evaluated the relationship between acquired resistance to clodronate treatment and BsmI, TaqI, and FokI VDR polymorphisms in Caucasian patients with polyostotic PDB (n = 84). We also evaluated the influence of mutations in exons 7 and 8 of the sequestosome 1 (SQSTM1) gene on the occurrence of this phenomenon. All patients were treated from diagnosis for several cycles with intravenous clodronate infusion (1500 mg/cycle). Acquired resistance to clodronate treatment was defined as the failure of total alkaline phosphatase serum levels to be suppressed to at least 50% of the patient’s previous highest levels during a subsequent treatment course with the same compound, which produced a >50% response after the first exposure. During an observation period of 10.6 ± 2.7 years, 31 PDB patients (36.9%) showed acquired resistance to clodronate. It was observed that the bb and TT VDR genotypes as well as a lower persistence of the biochemical response to the first treatment course were significantly and independently associated with the risk of developing resistance to clodronate treatment. SQSTM1 gene mutations, considered altogether, did not influence the occurrence of this phenomenon. Our results indicate that 3′VDR allelic variants and duration of biochemical response to the first treatment course are independent predictors of acquired resistance to clodronate treatment in patients with polyostotic PDB.
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Metadaten
Titel
Vitamin D Receptor Gene Polymorphisms Predict Acquired Resistance to Clodronate Treatment in Patients with Paget’s Disease of Bone
verfasst von
Giuseppe Mossetti
Luigi Gennari
Domenico Rendina
Gianpaolo De Filippo
Daniela Merlotti
Vincenzo De Paola
Pina Fusco
Teresa Esposito
Fernando Gianfrancesco
Giuseppe Martini
Ranuccio Nuti
Pasquale Strazzullo
Publikationsdatum
01.12.2008
Verlag
Springer-Verlag
Erschienen in
Calcified Tissue International / Ausgabe 6/2008
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-008-9193-7

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