Pharmacogenetics of Response to Bisphosphonate Treatment in Postmenopausal Osteoporosis: A Prospective Study
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Background: This study aims to investigate the effect of genetic polymorphisms of vitamin D receptor (VDR), estrogen receptor 1 (ER1), and Col1a1 on the response to bisphosphonate (BP) therapy in women with postmenopausal osteoporosis (OP). Methods: Twenty-one women with postmenopausal OP who received alendronate, ibandronate, or zoledronic acid for one year were enrolled in this study. Bone mineral density (BMD) at the lumbar spine and femoral neck were assessed by dual energy X-ray absorptiometry at baseline and after 12 months. Serum osteocalcin levels were measured at baseline and after 12 months. Polymorphic sites of the genes encoding ER1, VDR and Col1a1 proteins were amplified by polymerase chain reaction and examined using restriction fragment length polymorphism. Response to BP treatment and change in osteocalcin levels were compared among women with different gene polymorphisms. Results: Ratio of responders to treatment regarding improvements in the BMD of lumbar spine and femoral neck was adequate in 76% and 62%, respectively. There was no significant difference in treatment response regarding BMD in either region or change in serum osteocalcin levels among different gene polymorphisms. Conclusions: These findings did not support the potential role of VDR BsmI, Col1a1 Sp1, ER1 PvuII, or XbaI polymorphisms in predicting the response to BP therapy in women with postmenopausal OP. Further investigation with larger prospective studies is required.
Abstract
Background: This study aims to investigate the effect of genetic polymorphisms of vitamin D receptor (VDR), estrogen receptor 1 (ER1), and Col1a1 on the response to bisphosphonate (BP) therapy in women with postmenopausal osteoporosis (OP). Methods: Twenty-one women with postmenopausal OP who received alendronate, ibandronate, or zoledronic acid for one year were enrolled in this study. Bone mineral density (BMD) at the lumbar spine and femoral neck were assessed by dual energy X-ray absorptiometry at baseline and after 12 months. Serum osteocalcin levels were measured at baseline and after 12 months. Polymorphic sites of the genes encoding ER1, VDR and Col1a1 proteins were amplified by polymerase chain reaction and examined using restriction fragment length polymorphism. Response to BP treatment and change in osteocalcin levels were compared among women with different gene polymorphisms. Results: Ratio of responders to treatment regarding improvements in the BMD of lumbar spine and femoral neck was adequate in 76% and 62%, respectively. There was no significant difference in treatment response regarding BMD in either region or change in serum osteocalcin levels among different gene polymorphisms. Conclusions: These findings did not support the potential role of VDR BsmI, Col1a1 Sp1, ER1 PvuII, or XbaI polymorphisms in predicting the response to BP therapy in women with postmenopausal OP. Further investigation with larger prospective studies is required.