Influence of the Osteogenomic Profile in Response to Alendronate Therapy in Postmenopausal Women with Osteoporosis: A Retrospective Cohort Study

Abstract

Alendronate are used as the first line of pharmacological treatment for osteoporosis; however, some of them do not respond adequately to therapy with alendronate. The aim of this study was to investigate the influence of combinations of potential risk alleles (genetic profiles) associated with the response to antiosteoporotic treatment in a cohort consisting of 82 postmenopausal women with primary osteoporosis receiving alendronate (70 mg administered orally per week) for one year. Bone mineral density (BMD; g/cm2) of the femoral neck and lumbar spine was measured. According to BMD change patients were divided in two groups: responders and non-responders to alendronate therapy. Polymorphic variants in CYP19, ER, IL-6, PTHR1, TGFβ, OPG and RANKL genes were determined and profiles generating from the combination of risk alleles. Results: 56 subjects were responders to alendronate and 26 subjects were non-responders. The carriers of A-C-T-C profile (constructed from rs700518, rs1800795, rs2073618, and rs3102735) were predisposed to response to alendronate treatment (P= 0.001). Our findings highlight the importance of identified profiles for pharmacogenetics of alendronate therapy in osteoporosis.