title: Association of farnesyl diphosphate synthase polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis.
abstract: BACKGROUND
  Genetic factors are important in the pathogenesis of osteoporosis, but less is known about the genetic determinants of osteoporosis treatment. We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase (FDPS) in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.
  
  
  METHODS
  The study group comprised 639 postmenopausal women aged (62.2 ± 7.0) years with osteoporosis or osteopenia who had been randomly assigned to low dose group (70 mg/2 w) or standard dose group (70 mg/w) of alendronate in this 1-year study. We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul. Before and after treatment, serum levels of calcium, phosphate, alkaline phosphatase (ALP), cross linked C-telopeptide of type I collagen (β-CTX) were detected. Bone mineral density (BMD) at lumbar spine and proximal femur was measured. The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD, bone turnover biomarkers after the treatment.
  
  
  RESULTS
  The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck, and patients with CC genotype had significantly higher baseline femoral neck BMD ((733.6 ± 84.1) mg/cm(2)) than those with AC genotypes ((703.0 ± 86.9) mg/cm(2)) and AA genotypes ((649.8 ± 62.4) mg/cm(2)) (P < 0.01). No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS. The percentage change of serum ALP level was significantly lower in patients with CC genotype (-22.9%) than that in those with AC genotype (-24.1%) and AA genotype (-29.8%) of FDPS after 12 months of alendronate treatment (P < 0.05). Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.
  
  
  CONCLUSIONS
  FDPS gene was probably a candidate gene to predict femoral neck BMD at baseline. FDPS gene alleles could predict change percentage of ALP after treatment of alendronate, but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, People's Hospital of Liaocheng, Liaocheng, Shandong 252002, China.
authors.forename: Haijuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Email: limeilzh@sina.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Peiran
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
authors.affiliation: Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated with Shanghai Jiao Tong University, Shanghai 200233, China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Eryuan
authors.initials: E
authors.lastname: Liao
authors.affiliation: Department of Endocrinology, Osteoporosis Education Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Decai
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Liberation Army University, Xi'an, Shannxi 710032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Harbin Medical University Affiliated Second Hospital, Harbin, Heilongjiang 150081, China.
authors.forename: Tianzun
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Endocrinology, Guangdong General Hospital, Guangzhou, Guangdong 510080, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
mesh_terms: D019386:Alendronate / Q000627:therapeutic use*; D044466:Asian People; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D005260:Female; D051228:Geranyltranstransferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000235:genetics; D011110:Polymorphism, Genetic
chemical_list: D050071:Bone Density Conservation Agents; D051228:Geranyltranstransferase; D019386:Alendronate