Cindy Boer

138 | Chapter 3.2 Statistical analysis We evaluated the relation of VKA/antiplatelet to the risk of overall progression of OA of either the knee or hip using logistic regression with generalized estimating equations (GEE) to account for correlations between joints within an individual[18]. We repeated the analyses stratified by VKORC1 and MGP genotype/haplotype. The following covari- ates were included in all analyses: sex, age, BMI, physical activity, smoking, education level, Diabetes mellitus, hypertension, femoral neck BMD, HDL/total cholesterol ratio, baseline OA severity, time between follow-up visits, joint modeled and RS cohort ( Sup- plementary Text ). Results Relation of Acenocoumarol use to OA progression A total of 4,018 participants of two large prospective older-age population-based co- horts, the Rotterdam Study (RS), with RS-I, contributing 2,748 individuals, while RSII contributed 1,002 participants[14]. See Table 1 for the general characteristics of the study population. At baseline there were 358 individuals with OA (KLG ≥2), 75 with hip OA and 290 with knee OA. We identified 268 new users of acenocoumarol (VKA) (RS-I n=230, RS-II n=38) in our study population in our follow-up period. When we examined the incidence and progression of OA in acenocoumarol users and non-users, there was a >2-fold higher risk for overall OA incidence/progression (i.e., OA of the knee or hip) in acenocoumarol users compared with non-users (OR=2.50, 95% CI=1.94-3.20, Table 2 ). This association was also observed in each subcohort (RS-I and RS-II) separately ( Sup- plementary Table S2 ). Overall OA incidence/progression risk estimates remained similar for longer duration of acenocoumarol use (tertiles): ≤180 days (OR=2.82, 95% CI=1.90-4.20, >180 days and ≤556 days (OR=2.94, 95% CI=2.00-4.32), with only a re- duction of risk with long term use, >556 days of acenocoumarol use (OR=1.74, 95% CI = 1.10-2.76) ( Table 2 ). Increased risk of overall OA incidence/progression in acenocoumarol users was also observed in the knee and hip joints separately ( Table 2 ) [knee OA (OR=2.34, 95% CI=1.69-3.22) and hip OA(OR=2.74, 95% CI=1.82-4.11)], as well as in each subcohort separately ( Supplementary Table S2 ). Interestingly, longer duration of acenocouma- rol use do seem to have slight different effects om knee osteoarthritis incidence and progression than on hip. Knee OA risk seems to increase for longer duration of aceno- coumarol use, whereas risk for hip OA seems to decrease for longer durations of aceno-