title: A polymorphism at the translation start site of the vitamin D receptor gene is associated with the response to anti-osteoporotic therapy in postmenopausal women from southern Italy.
abstract: The present study investigated the effect of two single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, rs1544410 A/G and rs2228570 C/T, in modulating bone mineral density (BMD) and the response to treatment with bisphosphonates or strontium ranelate in postmenopausal osteoporosis (PMO). Four hundred eighteen postmenopausal women from Southern Italy treated with bisphosphonates or strontium ranelate for three years were enrolled and stratified according to their genotype. Changes in BMD were expressed as the delta t-score (Δt-score). Allelic frequencies for rs1544410 A/GSNP were 11.2% AA, 50.0% GA and 38.8% GG; for rs2228570 C/TSNP were 54.8% CC, 39.5% TC and 5.7% TT. TT carriers showed a lower t-score than TC and CC (both p < 0.02) genotypes and were more responsive to the therapy when compared to both TC (p < 0.02) and CC (p < 0.05) carriers. Specifically, TT carriers receiving alendronate demonstrated a significant improvement of the Δt-score compared to TC and CC (both p < 0.0001) carriers. After adjustment for confounders, the Δt-score showed evidence of a statistically significant positive association with TT in all treatments considered. Therapy response was independent of rs1544410 A/G SNP; instead, rs2228570 C/TSNP was associated with a better response to antiresorptive treatment, thus suggesting that the therapy for PMO should be personalized.
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy. vconti@unisa.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Conti
authors.affiliation: Doctoral School of Translational and Clinical Medicine, University of Salerno, Baronissi 84081, Italy. grussomanno@unisa.it.
authors.forename: Giusy
authors.initials: G
authors.lastname: Russomanno
authors.affiliation: Department of Medicine and Health Sciences, University of Molise, Campobasso 86100, Italy. graziamaria.corbi@unimol.it.
authors.forename: Graziamaria
authors.initials: G
authors.lastname: Corbi
authors.affiliation: Unit of Orthopaedics and Traumatology, "Martiri del Villa Malta" Hospital, Sarno 84087, Italy. giuseppe.toro@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toro
authors.affiliation: Laboratory of Pre-clinical and Translational Research, Reference Cancer Center of Basilicata, Scientific Institute of Hospitalization and Treatment, Rionero in Vulture 85028, Italy. vittoriosimeon@gmail.com.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Simeon
authors.affiliation: Department of Studies for Institutions and Territorial Systems, University "Parthenope" of Naples, Naples 80133, Italy. walter.filippelli@uniparthenope.it.
authors.forename: Walter
authors.initials: W
authors.lastname: Filippelli
authors.affiliation: Department of Medical Translational Sciences, University of Naples Federico II, Naples 80131, Italy. nicola.ferrara@unina.it.|Maugeri Foundation, Scientific Institute of Telese, IRRCS, Telese Terme 82037, Italy. nicola.ferrara@unina.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferrara
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Grimaldi
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples 80131, Italy. dargenio@ceinge.unina.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: D'Argenio
authors.affiliation: Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy. nmaffulli@unisa.it.|Centre for Sports and Exercise Medicine, Barts and the London School of Medicine and Dentistry, Mile End Hospital, 275 Bancroft Road, London E1 4DG, UK. nmaffulli@unisa.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Maffulli
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy. afilippelli@unisa.it.
authors.forename: Amelia
authors.initials: A
authors.lastname: Filippelli
mesh_terms: D019386:Alendronate / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007558:Italy; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D018167:Receptors, Calcitriol / Q000235:genetics*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D018167:Receptors, Calcitriol; D013876:Thiophenes; C579457:VDR protein, human; C081587:strontium ranelate; D019386:Alendronate