PurposeAlendronate is a widely used anti-osteoporotic drug. PFN1 gene is a newly identified early-onset Paget’s disease pathogenic gene. The purpose of this study is to study whether the genetic variations in this gene affect the clinical efficacy of alendronate in postmenopausal Chinese women with low bone mass.Patients and MethodsSeven single nucleotide polymorphisms in PFN1 gene were genotyped. A total of 500 postmenopausal women with osteoporosis or osteopenia were included. All participants were treated with weekly alendronate 70 mg for 12 months. A total of 466 subjects completed the follow-up. Bone mineral density (BMD) of lumbar spine, femoral neck and total hip were measured at baseline and after treatment.ResultsAfter 12 months of treatment, the BMD of lumbar spine, femoral neck and total hip all increased significantly (all P < 0.001), with an average increase of 4.72 ± 5.31%, 2.08 ± 4.45%, and 2.42 ± 3.46%, respectively. At baseline, there were no significant differences in BMD at lumbar spine, femoral neck and total hip between different genotype groups (P > 0.05). We failed to identify any significant association between the genotypes or haplotypes of PFN1 and the BMD response to alendronate therapy.ConclusionGenetic polymorphisms of PFN1 may not be a major contributor to the therapeutic response to alendronate treatment in Chinese women with low bone mass.