***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: objective To assess whether there is a relationship between the effectiveness of alendronate treatment in postmenopausal women with osteoporosis and BsmI vitamin D receptor ( VDR ) genotypes CONTEXT Osteoporosis is a systemic disease with a strong genetic component . Vitamin D receptor ( VDR ) gene polymorphisms explain only a small part of the genetic influence on the level of bone mineral density ( BMD ) , whereas their effect on fracture remains uncertain . OBJECTIVE The objective of this study was to investigate the relationships between VDR genotypes  and fracture risk . DESIGN A prospect i ve population -based cohort was studied . SUBJECTS A total of 589 postmenopausal women ( mean age , 62 yr ) were followed prospect ively during a median ( interquartile ) of 11 ( 1.1 ) yr . MAIN OUTCOME MEASURE The study measured incidents of vertebral and nonvertebral fractures . RESULTS VDR allele B was significantly and dose dependently overrepresented in women who fractured , including 34 and 86 women with first incident vertebral and nonvertebral fragility fractures , respectively . This corresponded to an odds ratio of 1.5 ( 95 % confidence interval , 0.95 - 2.40 ) for heterozygous carriers ( bB , n = 286 ) and 2.10 ( 95 % confidence interval , 1.16 - 3.79 ) for homozygous carriers ( BB , n = 90 ) of the B allele , compared with women with the bb genotype ( n = 213 ) . VDR genotype groups did not differ for demographics , physical activity , grip strength , personal and maternal history of fracture , and calcium intake . The association was independent of BMD of the spine , hip , and radius , and of the BMD loss at the radius . The relationship between VDR polymorphisms and fracture risk was not altered after adjustment for baseline circulating levels of bone turnover markers , estradiol , dehydroepi and rosterone sulfate , SHBG , IGF-I , intact PTH , and 25 hydroxyvitamin D. CONCLUSION VDR genotypes are associated with the risk of fracture  in postmenopausal women independently of BMD , rate of postmenopausal forearm BMD loss , bone turnover , and endogenous hormones . The mechanisms by which VDR genotypes influence bone strength remain to be determined Vitamin D receptor ( VDR ) gene polymorphisms could be considered one of the factors influencing the efficacy of the anti-osteoporotic treatments . In this multicenter , prospect i ve , r and omized and controlled trial we evaluated whether BsmI vitamin D receptor ( VDR ) genotypes influence the efficacy of antiresorptive treatment regimes ( administered alone or in combination ) in postmenopausal osteoporotic women . Using restriction endonuclease , we identified the BsmI VDR polymorphism in 1,100 postmenopausal women with osteoporosis . The women were r and omized , taking account of genotype , into five treatment groups : ( 1 ) alendronate ( Aln , 10 mg/day ) plus raloxifene ( Rlx , 60 mg/day ) ; ( 2 ) Aln plus hormone replacement therapy ( HRT , 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate ) ; ( 3 ) Aln alone ; ( 4 ) HRT alone ; and ( 5 ) Rlx alone .  Lumbar-spine bone mineral density ( BMD ) and bone turnover markers were measured at study entry and after 1 year of treatment . Using the general linear model ( GLM ) repeated- measures procedure , the means of BMD and bone turnover markers significantly differed from baseline after a period of treatment . In particular , the mean change from baseline for BMD was −0.034 ( 95 % confidence interval [ CI ] : −0.037 to −0.031 , P < 0.001 ) ; for serum osteocalcin ( OC ) it was 1.369 ( 95 % CI : 1.289 to 1.448 , P < 0.001 ) ; and for urinary deoxypyridinoline ( DPD ) it was 1.322 ( 95 % CI : 1.242 to 1.401 , P < 0.001 ) , indicating a considerable variation before and after treatment of these indicators . In all three cases these effects appeared significantly influenced by treatments , genotypes , and the treatments*genotypes interaction term ( P < 0.001 each , except for the BMD and genotype effect with P = 0.02 ) , and not by the investigational centers involved in the study . In conclusion , in postmenopausal osteoporotic women , BsmI VDR genotypes influence the efficacy of antiresorptive drugs  particularly when used in combination A novel T/C polymorphism ( ATG to ACG ) at the translation initiation site of the vitamin D receptor ( VDR ) gene , defined by FokI restriction endonuclease , has been recently associated with variation in bone mineral density ( BMD ) and rates of bone loss in a group of postmenopausal Mexican-American women . The presence of the restriction site , design ated as f , allows protein translation to initiate from the first ATG , while the allele lacking the site , indicated as F , initiates translation at a second ATG . In this study , we investigated the role of FokI polymorphism in a group of 400 postmenopausal women of Italian descent stratified for BMD into osteoporotic ( n = 164 ) , osteopenic ( n = 117 ) , and normal ( n = 119 ) groups . There were 159 ( 41 % ) FF homozygotes , 55 ( 14 % ) ff homozygotes , and 186 ( 45 % ) Ff heterozygotes . In the whole population , we observed a weak association between FokI polymorphism and lumbar BMD ( p = 0.06 , analysis of covariance [ ANCOVA ] ) but not with femoral neck BMD ( p = 0.5 , ANCOVA ) . Interestingly , the effect of FokI genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greater among women in the first 5 years of menopause ( p = 0.04 , ANCOVA ) , progressively declining afterward . In addition , a significantly higher prevalence of ff genotype in osteoporotic than in osteopenic and normal women was observed ( p = 0.04 , Chi-square test ) . Finally , ff genotype result ed significantly over-represented in the group of women with a vertebral fracture as compared with controls ( p = 0.003 , Chi-square test ) , equivalent to a relative risk of 2.58 ( 95 % confidence intervals 1.36 - 4.91 ) . We conclude that in this population , FokI polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine 
    Output:
    
Overall , there were significant correlations between VDR ApaI , VDR FokI and PMOP susceptibility .
Subgroup analysis showed that VDR ApaI polymorphism significantly decreased the osteoporosis risk in Caucasian postmenopausal women .
In Asian population s , VDR BsmI and VDR FokI were associated with an increased risk of PMOP .
As to the associations between VDR polymorphisms and BMD , Caucasian PMOP women carrying the ApaI aa genotype were at risk of high BMD in femoral neck , and low femoral neck BMD was observed in Caucasian PMOP women with FokI Ff genotype .
PMOP women with the Cdx2 GA genotype had a lower lumbar spine BMD in overall and Caucasian population s compared with PMOP women with GG genotype .
Different VDR gene polymorphisms have different impacts on PMOP risk and BMD