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Bone Abstracts (2014) 3 PP186 | DOI: 10.1530/boneabs.3.PP186


Pharmacogenomics of bisphosphonate treatment in Paget's disease of bone: retrospective and prospective analysis

Daniela Merlotti1, Fernando Gianfrancesco2, Domenico Rendina3, Riccardo Muscariello3, Teresa Esposito2, Maria Beatrice Franci1, Barbara Lucani1, Maria Stella Campagna1, Laura Cresti1, Pasquale Strazzullo3, Ranuccio Nuti1 & Luigi Gennari1


1Department of Medicine, Surgery and Neurosciences University of Siena, Siena, Italy; 2Institute of Genetics and Biophysics - National Research Council of Italy, Naples, Italy; 3Department of Clinical and Experimental Medicine, University of Naples Federico II, Naples, Italy.

We previously evidenced a reduced response to i.v. pamidronate in Q15STM1 mutation carriers (Q15STM1+) with Paget’s disease of bone (PDB). In order to confirm and extend this observation, we investigated the effect of Q15STM1 mutation and polymorphisms in three genes associated with PDB (TNFRSF11A; OPTN; TNFRSF11B) on the response to bisphosphonates. First, a retrospective study was performed in 335 patients treated with i.v. clodronate (CLN) 1500 mg/6 months (n=84), i.v. pamidronate (PAM) 60 mg/6 months (n=75), risedronate (RIS) 30 mg/day for 2 months (n=57), neridronate (NER) 200 mg i.m. or i.v. (n=61) and zoledronate (ZOL) 4 mg or 5 mg i.v. (n=48). Overall, Q15STM1+ patients had an increased disease severity and a reduced response to CLN or PAM than Q15STM1− patients. Despite carriers of TNFRSF11A rs1805034 CC genotype had increased PDB severity, there was no association between this genotype and the response to any treatment. Conversely, there was an increased prevalence of TT carriers of rs1561570 (OPTN) in non-responders to CLN. Normalization after the first CLN course was achieved in 69% of CC vs 42% of TT carriers despite no significant differences in disease extension or activity, especially in Q15STM1− patients. A similar but not significant trend was observed for PAM. Conversely, RIS, ZOL and NER were effective in most patients. We then designed a prospective analysis in patients treated with iv ZOL 5 mg (n=130) or NER 200 mg (n=70) and followed-up for more than 3 years. Even though most patients achieved biochemical remission after the first NER course for more than 12 months, there was a trend for an earlier relapse in Q15STM1+ vs Q15STM1−patients. Conversely most ZOL treated patients achieved biochemical remission independent of Q15STM1 mutation and did not need retreatment. These results suggest that PDB patients with Q15STM1 mutation may require a more aggressive treatment regimen for long-term disease remission.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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