Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study in a large health management organization

Abstract

Objective: Millions of women in the United States and across the globe abruptly discontinued postmenopausal hormone therapy (HT) after the initial Women's Health Initiative trial publication. Few data describing the effects of HT cessation on hip fracture incidence in the general population are available. We evaluated the impact of HT cessation on hip fracture incidence in a large cohort from the Southern California Kaiser Permanente health management organization.

Methods: In this longitudinal observational study, 80,955 postmenopausal women using HT as of July 2002 were followed up through December 2008. Data on HT use after July 2002, antiosteoporotic medication use, and occurrence of hip fracture were collected from the electronic medical record system. Bone mineral density (BMD) was assessed in 54,209 women once during the study period using the dual-energy x-ray absorptiometry scan.

Results: After 6.5 years of follow-up, age- and race-adjusted Cox proportional hazard models showed that women who discontinued HT were at 55% greater risk of hip fracture compared with those who continued using HT (hazard ratio, 1.55; 95% CI, 1.36-1.77). Hip fracture risk increased as early as 2 years after cessation of HT (hazard ratio, 1.52; 95% CI, 1.26-1.84), and the risk incrementally increased with longer duration of cessation (P for trend < 0.0001). Longer duration of HT cessation was linearly correlated with lower BMD (β estimate [SE]) = -0.13 [0.003] T-score SD unit per year of HT cessation; P < 0.0001).

Conclusions: Women who discontinued postmenopausal HT had significantly increased risk of hip fracture and lower BMD compared with women who continued taking HT. The protective association of HT with hip fracture disappeared within 2 years of cessation of HT. These results have public health implications with regard to morbidity and mortality from hip fracture.

FIG. 1

Trend in annual HT use (percent) and age-standardized hip fracture IRs between 2002 and 2008. Note that the female population in California from Census 2000 was used as the standard population to calculate the age-standardized rates. The rate for 2002 was divided by 0.50 because the data during the 6-month period (July-December) were used. The difference in the number of women available for hip fracture rate and HT use prevalence rate is due to missing HT use data in years 2004, 2005, 2006, 2007, and 2008. HT, hormone therapy; IR, incidence rate.

FIG. 2

T scores in relation to years of not using HT since 2002. Note the mean BMD T-scores by cumulative years of HT nonuse before the year of DXA scan in 54,209 women. The linear regression model was adjusted for age, race, BMI, bisphosphonate use at the time of DXA scan, and year of DXA scan. HT, hormone therapy; BMD, bone mineral density; DXA, dual-energy x-ray absorptiometry; BMI, body mass index.