[Osteoprotegerin gene polymorphism and therapeutic response to alendronate in postmenopausal women with osteoporosis].
OBJECTIVE
To investigate whether the polymorphism of osteoprotegerin (OPG) gene is associated with the change of BMD (bone mineral density) after alendronate therapy in postmenopausal women with osteoporosis and determine the correlation between genotypes and therapeutic effect.


METHODS
Eighty postmenopausal osteoporotic patients were recruited with an average age of (64.2 +/- 7.7) years old. Every patient took oral alendronate (Fosamax) 70 mg weekly and Caltrate 600 mg daily for 12 months. At pre- and post-treatment, BMD was measured at lumbar spine 2 - 4 and hip sites. PCR-RFLP was performed for three polymorphisms at the promoter site of OPG gene (A163G, T245G and T950C).


RESULTS
One-year therapy was accomplished in 67 patients. Patients with G allele (genotype AG and GG) of site A163G, the baseline BMD of vertebral L2-4, inter-troche and total hip were lower than genotype AA [(0.732 +/- 0.113) g/cm(2) vs (0.819 +/- 0.157) g/cm(2), (0.775 +/- 0.101) g/cm(2) vs (0.843 +/- 0.124) g/cm(2) and (0.667 +/- 0.105) g/cm(2) vs (0.725 +/- 0.091) g/cm(2)]. Patients with G allele (genotype TG and GG) of site T245G, baseline BMD of vertebral L2-4, inter-troche and total hip were lower than genotype TT [(0.723 +/- 0.111) g/cm(2) vs (0.819 +/- 0.155) g/cm(2), (0.776 +/- 0.102) g/cm(2) vs (0.840 +/- 0.124) g/cm(2) and (0.670 +/- 0.109) g/cm(2) vs (0.721 +/- 0.091) g/cm(2)]. After one-year therapy, at site A163G, the percentage of BMD change at inter-troche was higher in genotype AA than in genotypes AG and GG [2.50 (3.47)% vs 0.88% (3.47%)%, P = 0.014]. While at site T245G, the percentage of BMD change at inter-troche and total hip were higher in genotype TT than in genotype TG and GG 2.50% (3.47%) vs 0.61% (3.31%), P = 0.011; 2.72% (2.68%) vs 0.89 (3.01%), P = 0.046].


CONCLUSIONS
The G allele of sites A163G and T245G may be the risk allele of postmenopausal osteoporosis. Furthermore, patients with genotypes AA (A163G) and (T245G) show a better therapeutic effect to alendronate.
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Chun
C
Wang
Jin-wei
JW
He
Yue-juan
YJ
Qin
Hao
H
Zhang
Wei-wei
WW
Hu
Yu-juan
YJ
Liu
Zhen-lin
ZL
Zhang
D000368:Aged; D019386:Alendronate / Q000627:therapeutic use; D000483:Alleles; D015519:Bone Density; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D053244:Osteoprotegerin / Q000235:genetics* / Q000627:therapeutic use; D011110:Polymorphism, Genetic
D053244:Osteoprotegerin; D019386:Alendronate