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BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial

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Abstract

Vitamin D receptor (VDR) gene polymorphisms could be considered one of the factors influencing the efficacy of the anti-osteoporotic treatments. In this multicenter, prospective, randomized and controlled trial we evaluated whether BsmI vitamin D receptor (VDR) genotypes influence the efficacy of antiresorptive treatment regimes (administered alone or in combination) in postmenopausal osteoporotic women. Using restriction endonuclease, we identified the BsmI VDR polymorphism in 1,100 postmenopausal women with osteoporosis. The women were randomized, taking account of genotype, into five treatment groups: (1) alendronate (Aln, 10 mg/day) plus raloxifene (Rlx, 60 mg/day); (2) Aln plus hormone replacement therapy (HRT, 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate); (3) Aln alone; (4) HRT alone; and (5) Rlx alone. Lumbar-spine bone mineral density (BMD) and bone turnover markers were measured at study entry and after 1 year of treatment. Using the general linear model (GLM) repeated-measures procedure, the means of BMD and bone turnover markers significantly differed from baseline after a period of treatment. In particular, the mean change from baseline for BMD was −0.034 (95% confidence interval [CI]: −0.037 to −0.031, P <0.001); for serum osteocalcin (OC) it was 1.369 (95% CI: 1.289 to 1.448, P <0.001); and for urinary deoxypyridinoline (DPD) it was 1.322 (95% CI: 1.242 to 1.401, P <0.001), indicating a considerable variation before and after treatment of these indicators. In all three cases these effects appeared significantly influenced by treatments, genotypes, and the treatments*genotypes interaction term (P <0.001 each, except for the BMD and genotype effect with P =0.02), and not by the investigational centers involved in the study. In conclusion, in postmenopausal osteoporotic women, BsmI VDR genotypes influence the efficacy of antiresorptive drugs particularly when used in combination.

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Acknowledgements

This research was supported by the “Programma Operativo Plurifondo (POP)”, Campania Region, Italy. The authors thank Dr. Benito Chinea (Ibis, Milan) and Mrs. Jean Ann Gilder (Scientific Communication) for editing the text. No financial support was provided by any pharmaceutical company to realize the present research

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University Magna Graecia of Catanzaro, Catanzaro, Italy

    Stefano Palomba, Tiziana Russo, Angela Falbo & Fulvio Zullo

  2. Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples, Naples, Italy

    Francesco Orio Jr. & Gaetano Lombardi

  3. Department of Gynaecology Obstetrics and Human Reproduction, University Federico II of Naples, Naples, Italy

    Achille Tolino

  4. Department of Internal Medicine, University Federico II of Naples, Naples, Italy

    Francesco Manguso

  5. Department of Clinical and Experimental Medicine, University Federico II of Naples, Naples, Italy

    Vincenzo Nunziata

  6. Department of Obstetrics and Gynaecology, University of Messina, Messina, Italy

    Pasquale Mastrantonio

  7. Via E. Nicolardi 188, 80131, Naples, Italy

    Stefano Palomba

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  1. Stefano Palomba
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  2. Francesco Orio Jr.
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Correspondence to Stefano Palomba.

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Palomba, S., Orio, F., Russo, T. et al. BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial. Osteoporos Int 16, 943–952 (2005). https://doi.org/10.1007/s00198-004-1800-5

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