Linear regression analyses were used to evaluate the association between blood parameters and BMD. Generalized additive regression models (GAMs), as implemented in S-PLUS 6.2 for Windows (Insightful Corporation, Seattle, Wash) were used to generate graphic representations of the dose-response relations between levels of tHcy, folate, and vitamin B12 and BMD, adjusted for covariates.26 A variable was included as a covariate to control for confounding if it affected the β-coefficient in the tHcy-BMD linear regression by 5% or more in any of the age- and sex-specific strata (change-in-estimate criterion for confounder selection).27 By this procedure our final model included the following covariates: BMI, smoking status, consumption of coffee, plasma creatinine level, level of physical activity, and use of postmenopausal estrogen (women only). Height, weight, age, intake of calcium and vitamin D, and for women, previous use of estrogen and years since menopause were considered but not included. Plasma tHcy level was divided into 4 categories: less than 9.0 μmol/L (reference), 9.0-11.9 μmol/L, 12.0-14.9 μmol/L, and 15 μmol/L or greater (<1.22 mg/L [reference], 1.22-1.61 mg/L, 1.62-2.01 mg/L, and ≥2.02 mg/L).2,28 Folate and vitamin B12 were also divided into 4 categories: plasma folate, less than 3.80 nmol/L, 3.80-4.99 nmol/L, 5.00-8.49 nmol/L, and 8.50 nmol/L or greater (reference) (<1.68 ng/mL, 1.68-2.20 ng/mL, 2.21-3.74 ng/mL, and ≥3.75 ng/mL [reference]); plasma vitamin B12, less than 230.0 pmol/L, 230.0-279.9 pmol/L, 280.0-414.9 pmol/L, and ≥415.0 pmol/L (reference) (<311.65 pg/mL, 311.65-379.39 pg/mL, 379.40-562.32 pg/mL, and ≥562.33 pg/mL [reference]).28 Low BMD was defined as BMD in the lowest quintile for each sex and age group. The BMD cutoff for men was 0.918 g/cm2 for the youngest and 0.829 g/cm2 for oldest age group. The corresponding cutoff values for women were 0.874 g/cm2 and 0.693 g/cm2. Logistic regression analyses were used to estimate odds ratios (ORs) for low BMD comparing each category of plasma tHcy, folate, or vitamin B12 level with the reference category. Linear representation of indicator variables was used to test for trend.