Hormone replacement therapy and hip fracture risk: Effect modification by tobacco smoking, alcohol intake, physical activity, and body mass index

The authors prospectively studied the overall effect of hormone replacement therapy (HRT) on hip fracture risk and the effect modification by behavior al habits and body mass index. A total of 6,159 postmenopausal women from t he Copenhagen Center for Prospective Population Studies, Copenhagen, Denmar k, with initial examination in 1976-1978 were followed until 1993. During f ollow-up 363 hip fractures were identified. Women who reported current use of HRT had a lower risk of hip fracture as compared with women who were non users (relative risk (RR) = 0.71; 95 percent confidence interval (CI): 0.50 , 1.01), Use of HRT was associated with a lower risk of hip fracture in for mer (RR = 0.55; 95 percent CI: 0.22, 1.37) and current (RR = 0.61; 95 perce nt CI: 0.38, 0.99) smokers but not in never smokers (RR = 1.10; 95 percent CI: 0.60, 2.03). HRT was also associated with lower risk of hip fracture am ong alcohol drinkers (RR = 0.36; 95 percent CI: 0.14, 0.90) and among seden tary women (RR = 0.42; 95 percent CI: 0.18, 0.98) but not among nondrinkers (RR = 0.99; 95 percent CI: 0.61, 1.61) and physically active women (RR = 0 .92; 95 percent CI: 0.42, 2.04). There was no evidence of interaction betwe en use of HRT and body mass index. In conclusion, the protective effect of HRT on hip fracture appears to be strongest in women who ever smoked, in wo men who drink alcohol, and in women who are sedentary. The results suggest that history of behavioral habits offers important information concerning t he probable degree of protection against hip fracture afforded by HRT.