Variation in the Efficacy of Hormone Replacement Therapy in the Prevention of Hip Fracture

Abstract

Use of postmenopausal hormone replacement therapy (HRT) has been associated with a reduced risk of osteoporotic fractures. However, it is uncertain whether this risk reduction is modified by other risk factors for hip fracture. In a population-based case-control study in Sweden, we investigated the association between HRT and hip fracture risk within categories of age, body measures and lifestyle factors in postmenopausal women, 50-81 years of age. Mailed questionnaires and telephone interviews were used to collect data. Of those eligible, 1328 incident cases with hip fracture (82.5%) and 3312 randomly selected controls (81.6%) answered the questionnaire. Ever use of HRT in women less than 75 years old was associated with an odds ratio (OR) of 0.66 (95% confidence interval: 95% CI 0.50-0.87) for hip fracture compared with OR 0.40 (95% CI 0.21-0.77) in women 75 years or older. We found a significant interaction between HRT and both weight and physical activity (p < 0.05). The protective effect of HRT was particularly pronounced in lean women: compared with never HRT users, ever users weighing under 60 kg had an OR of 0.44 (95% CI 0.30-0.66) whereas women weighing more than 70 kg had an OR of 0.91 (95% CI 0.53-1.56). Women with low recent leisure physical activity (less than 1 h/week) similarly benefited more from HRT for hip fracture prevention than women with a higher degree of recreational physical activity. The observed interactions with weight and physical activity suggest that HRT has the best protective effect against hip fracture among high-risk women.

Trends in hip fracture incidence and in the prescription of antiosteoporosis medications during the same time period in Belgium (2000–2007)

“…It is also a limitation of the present study that hormone replacement therapy (HRT) was not accounted for in our study as an osteoporosis medication because of the pleiotropic actions of substitution therapy in elderly women. Although HRT is no longer considered as a first-line treatment for osteoporosis, in postmenopausal women without climacteric symptoms, it is well recognized that HRT has a protective effect on fracture risk (36), with variation in the efficacy according to risk factors (37,38). One cannot rule out that part of the reduction in fracture incidence observed in women is related to the widespread use of estrogens, particularly before the publication of the Women's Health Initiative study.…”

Bone turnover and body weight relationships differ in normal-weight compared with heavier postmenopausal women

“…However, baseline values (such as the presence of fractures prior to therapy in some subjects) make these data difficult to interpret in at least one of these studies [26]. Bjarnason and Christiansen [27] found that BMI did not influence the response to HRT treatment, whereas a large study evaluating postmenopausal risk factors for hip fracture found that the best protective effect of HRT was among leaner women [28]. Our BMC results using a wider range of body weights are consistent with these findings.…”

Estrogen therapy for postmenopausal osteoporosis

“…Epidemiologic studies also support these studies in that reductions in fracture risk that are obtained with HT are lost after discontinuation of therapy. In some studies, women who discontinued therapy had rates of fracture and bone loss similar to those who had never taken HT (54,55).…”