AUTHOR=Wawrzyniak Anna , Skrzypczak-Zielińska Marzena , Michalak Michał , Kaczmarek-Ryś Marta , Ratajczak Alicja Ewa , Rychter Anna Maria , Skoracka Kinga , Marcinkowska Michalina , Słomski Ryszard , Dobrowolska Agnieszka , Krela-Kaźmierczak Iwona 

TITLE=Does the VDR gene polymorphism influence the efficacy of denosumab therapy in postmenopausal osteoporosis?

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1063762

DOI=10.3389/fendo.2022.1063762

ISSN=1664-2392

ABSTRACT=<sec><title>Introduction</title><p>One of the challenges of personalized medicine is a departure from traditional pharmacology toward individualized, genotype-based therapies. Postmenopausal osteoporosis is a prevalent condition requiring intensive treatment, whose effects are measurable only after a long time, and the goal is bone fracture prevention. This study aimed to determine the influence of <italic>VDR</italic> gene variation on anti-osteoporotic one-year treatment with denosumab in 63 Polish women with postmenopausal osteoporosis.</p></sec><sec><title>Materials and methods</title><p>The correlation between bone mineral density (BMD) of the lumbar vertebral column (L1–L4) and femoral neck, and genotype distributions for the <italic>ApaI</italic>, <italic>BsmI</italic>, <italic>FokI</italic>, and <italic>TaqI</italic> variants of the <italic>VDR</italic> gene was analyzed. Bone fractures during denosumab therapy were also investigated.</p></sec><sec><title>Results</title><p>In the case of the <italic>Bsml</italic> polymorphism, female patients with BB and Bb genotypes had statistically significantly higher values of BMD and T-score/Z-score indicators, which persisted after a year of denosumab treatment. Our results indicated that the <italic>Bsml</italic> polymorphism contributes to better bone status, and, consequently, to more efficient biological therapy. The study did not reveal significant differences between changes (delta) in BMD and genotypes for the analyzed <italic>VDR</italic> gene <italic>loci</italic>. In the entire study group, one bone fracture was observed in one patient throughout the yearlong period of denosumab therapy.</p></sec><sec><title>Conclusions</title><p>BB and Bb genotypes of the <italic>Bsml</italic> polymorphism of the <italic>VDR</italic> gene determine higher DXA parameter values both before and after one-year denosumab therapy in postmenopausal women with osteoporosis.</p></sec>