RESULTS The meta- analysis of observational studies showed a weaker slope of dose-response relations than the meta- analysis of RCTs .
The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of population
BACKGROUND Many r and omized controlled trials ( RCTs ) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers .
The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence .
OBJECTIVE We systematic ally review ed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12  status and estimated dose-response relations with the use of a meta- analysis .
Homocysteine levels and the risk of osteoporotic fracture.
BACKGROUND Very high plasma homocysteine levels are characteristic of homocystinuria , a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis . We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures . METHODS We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects , 55 years of age or older , who participated in two separate prospect i ve , population -based studies . In the Rotterdam Study , there were two independent cohorts : 562 subjects in cohort 1 , with a mean follow-up period of 8.1 years ; and 553 subjects in cohort 2 , with a mean follow-up period of 5.7 years . In the Longitudinal Aging Study Amsterdam , there was a single cohort of 1291 subjects , with a mean follow-up period of 2.7 years . Multivariate Cox proportional-hazards regression models were used for analysis of the risk of fracture , with adjustment for age , sex , body-mass index , and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels . RESULTS During 11,253 person-years of follow-up , osteoporotic fractures occurred in 191 subjects . The overall multivariable-adjusted relative risk of fracture was 1.4 ( 95 percent confidence interval , 1.2 to 1.6 ) for each increase of 1 SD in the natural-log-transformed homocysteine level . The risk was similar in all three cohorts studied , and it was also similar in men and women . A homocysteine level in the highest age-specific quartile was associated with an increase by a factor of 1.9 in the risk of fracture ( 95 percent confidence interval , 1.4 to 2.6 ) . The associations between homocysteine levels and the risk of fracture appeared to be independent of bone mineral density and other potential risk factors for fracture . CONCLUSIONS An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women
RESULTS The meta- analysis of observational studies showed a weaker slope of dose-response relations than the meta- analysis of RCTs .
The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of population
BACKGROUND Many r and omized controlled trials ( RCTs ) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers .
The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence .
OBJECTIVE We systematic ally review ed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12  status and estimated dose-response relations with the use of a meta- analysis .