The aim of this study was to investigate the relationship between aortic calcification (AC) and low bone mineral density (BMD), 25(OH)D, C-terminal telopeptide (CTx), and osteocalcin levels in Asian women. We also tried to find the association between AC and the risk of vertebral fracture. We included 769 patients in this study. All patients underwent QCT. Aortic calcium score (ACS) was quantified by the Agatston scoring method. Spinal fracture was defined by lumbar spine radiography. Among 769 subjects, 96 had at least one vertebral fracture and 345 had AC. ACS positively correlated with age. Osteocalcin, CTx, 25(OH)D, total-hip trabecular BMD (tBMD), femoral neck tBMD, and vertebral tBMD were inversely related with ACS. However, cortical BMD (cBMD) did not correlate with ACS. Among these parameters, only osteocalcin significantly correlated with ACS, even after adjusting for age. We divided the subjects into two groups based on the presence of AC to determine the association between AC and vertebral fracture. Multivariate logistic regression analysis showed that age, tBMD of each site, and AC were associated with vertebral fractures. After adjusting for confounding factors, patients with AC had more than a threefold increased risk of vertebral fracture (OR = 3.29-3.57, P < 0.05 according to site). This study suggests that high ACS is related to low tBMD but not cBMD. Furthermore, our findings indicate that this relationship is definitely age-dependent. Finally, we found that AC is significantly associated with the prevalence of vertebral fracture in Asian women.
S-warfarin area under the concentration-time curve (AUC(0- infinity )) and clearance are used as measures of cytochrome p450 (CYP) 2C9 activity. In addition, warfarin S/R ratios are used to assess CYP2C9 activity. The determination of S-warfarin AUC(0- infinity ) requires multiple blood samples. Limited sampling strategy (LSS) is a validated technique that estimates AUC(0- infinity ) using limited blood samples. The objective of this study was to evaluate LSS of S-warfarin concentrations and warfarin S/R ratios to predict S-warfarin AUC(0- infinity ) during CYP2C9 baseline activity and inhibition with fluvastatin. Fifty-one healthy subjects, genotyped as CYP2C9 extensive metabolizers, were administered oral warfarin 10 mg. Blood samples were collected over 96 hours. S-warfarin AUC(0- infinity ) equations were derived from a training set of 20 subjects using multiple linear regression. Validation of the equations used data from the remaining 31 subjects. All derived equations were within acceptable limits for measures of bias and precision. Single-point and two-point S-warfarin concentrations, but not warfarin S/R ratios, were predictive of S-warfarin AUC(0- infinity ) during CYP2C9 baseline activity and inhibition. No correlation was observed between CYP2C9(*)1/(*)1 and (*)1/(*)2 genotypes and either S-warfarin concentrations or warfarin S/R ratios. The equation using two-point S-warfarin concentrations at 24 and 48 hours was the most accurate predictor of S-warfarin AUC(0- infinity ). LSS using S-warfarin concentrations is an efficient and accurate technique to evaluate S-warfarin AUC(0- infinity ) when using warfarin as a CYP2C9 probe drug.
Cigarette smoking does not affect CYP2C9 activity as evaluated using S-warfarin as a CYP2C9 probe. Fluvastatin is a weak inhibitor of CYP2C9 activity in both smokers and non-smokers.
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