Estradiol, Testosterone, and the Risk for Hip Fractures in Elderly Men from the Framingham Study

Abstract Background Low serum estradiol has been more strongly associated with low bone mineral density in elderly men than has testosterone, but its association with incident hip fracture is unknown. We examined whether low estradiol increases the risk for future hip fracture among men and explored whether testosterone levels influence this risk. Methods We examined 793 men (mean age = 71 years) evaluated between 1981 and 1983, who had estradiol measures and no history of hip fracture, and followed until the end of 1999. Total estradiol and testosterone were measured between 1981 and 1983. Hip fractures were identified and confirmed through medical records review through the end of 1999. We created 3 groups of men based on estradiol levels and performed a Cox-proportional hazards model to examine the risk for incident hip fracture, adjusted for age, body mass index, height, and smoking status. We performed similar analyses based on testosterone levels, and then based on both estradiol and testosterone levels together. Results There were 39 men who sustained an atraumatic hip fracture over follow-up. Incidence rates for hip fracture (per 1000 person-years) were 11.0, 3.4, and 3.9 for the low (2.0-18.1 pg/mL [7-67 pmol/L]), middle (18.2-34.2 pg/mL [67-125 pmol/L]), and high (≥34.3 pg/mL [≥126 pmol/L]) estradiol groups, respectively. With adjustment for age, body mass index, height, and smoking status, the adjusted hazard ratios for men in the low and middle estradiol groups, relative to the high group, were 3.1 (95% confidence interval [CI], 1.4-6.9) and 0.9 (95% CI, 0.4-2.0), respectively. In similar adjusted analyses evaluating men by their testosterone levels, we found no significant increased risk for hip fracture. However, in analyses in which we grouped men by both estradiol and testosterone levels, we found that men with both low estradiol and low testosterone levels had the greatest risk for hip fracture (adjusted hazard ratio: 6.5, 95% CI, 2.9-14.3). Conclusion Men with low estradiol levels are at an increased risk for future hip fracture. Men with both low estradiol and low testosterone levels seem to be at greatest risk for hip fracture.