Association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride on bone mineral density and bone turnover markers in postmenopausal women with osteoporosis.
OBJECTIVE
To investigate the association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride(RLX) on bone mineral density (BMD) and bone turnover markers in postmenopausal women with osteoporosis.


METHODS
A total of 68 unrelated postmenopausal women with osteoporosis of Han ethnicity aged 47-74 years were randomly divided into 2 groups of 34 women: RLX group (60 mg were given daily for 12 months) and placebo group. BMD and bone turnover markers were measured at baseline, 6 and 12 months after treatment. The polymorphisms of Xba I and Pvu II sites in estrogen receptor 1 gene(ESR1), Ras I site in ESR2 gene, and start codon (Fok I) and CDX2 binding sites in vitamin D receptor gene (VDR) were analyzed.


RESULTS
A total of 58 patients completed 12 months of study period. By the end of study, the increased percentage of BMD in lumbar spine 2-4 (L2-4), total hip, and trochanter were found significantly different between RLX group and placebo group(P<0.05), and the decreased percentage of C-telopeptide and osteocalcin were significantly different between the two groups (P<0.01). The BMD of total hip and trochanter of women with FF genotypes of VDR Fok I site were decreased by 1.98%+/-4.86% and 2.26%+/-4.73% respectively in the RLX group, but those of women with Ff/ff genotypes were increased by 2.52%+/-2.75% and 2.74 %+/-2.97%, respectively(P<0.05). Moreover, the total hip BMD of women with PP/Pp genotypes of ESR1 Pvu II site was increased by 2.12%+/-2.78%, and of women with pp genotype it was decreased by 1.34%+/-3.73%(P<0.05). However, no significant association was observed of the polymorphisms of five sites with the changes of BMD and bone turnover markers in the placebo group.


CONCLUSIONS
The effect of RLX on BMD in postmenopausal women with osteoporosis is regulated by the polymorphisms of Fok I of VDR gene and Pvu II of ESR1 gene. The study is valuable to select this drug according to genotype of patients in clinical.
Zhang
Zhen-lin
ZL
Center for Preventing and Treating Osteoporosis, Osteoporosis Research Unit, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, 200233 P.R.China. ZZL2002@medmail.com.cn
He
Jin-wei
JW
Qin
Yue-juan
YJ
Huang
Qi-ren
QR
Liu
Yu-juan
YJ
Hu
Yun-qiu
YQ
Li
Miao
M
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects* / Q000235:genetics; D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects* / Q000235:genetics; D001842:Bone and Bones / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000187:drug effects; D020849:Raloxifene Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014930:Women
D015415:Biomarkers; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride