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ContextThe Women's Health Initiative (WHI) hormone therapy (HT) trials showed protection against hip and total fractures, but a later observational report suggested loss of benefit and a rebound increased risk after cessation of HT.ObjectiveThe purpose of this study was to examine fractures after discontinuation of HT.Design and settingTwo placebo-controlled randomized trials served as the study setting.PatientsStudy patients included WHI participants (N = 15,187) who continued active HT or placebo through the intervention period and who did not take HT in the postintervention period.InterventionsTrial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) in naturally menopausal women and CEE alone in women with prior hysterectomy.Main outcome measuresTotal fractures and hip fractures through 5 years after discontinuation of HT were recorded.ResultsHip fractures were infrequent (∼2.5 per 1000 person-years); this finding was similar between trials and in former HT and placebo groups. There was no difference in total fractures in the CEE + MPA trial for former HT vs former placebo users (28.9 per 1000 person-years and 29.9 per 1000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87 to 1.09; P = 0.63); however, in the CEE-alone trial, total fractures were higher in former placebo users (36.9 per 1000 person-years) compared with the former active group (31.1 per 1000 person-years), a finding that was suggestive of a residual benefit of CEE against total fractures (HR, 0.85; 95% CI, 0.73 to 0.98; P = 0.03).ConclusionsWe found no evidence for increased fracture risk, either sustained or transient, for former HT users compared with former placebo users after stopping HT. There was residual benefit for total fractures in former HT users from the CEE-alone study.

ContextVasomotor symptoms (VMS) are common. Whether VMS are associated with fracture incidence or bone mineral density (BMD) levels is unknown.ObjectiveThis study aimed to examine associations of baseline VMS with fracture incidence and BMD.DesignThis was a prospective observational study with mean (SD) followup of 8.2 (1.7) years (1993-2005).SettingForty United States clinical centers.ParticipantsWe examined data from Women's Health Initiative Clinical Trial participants (n = 23 573) age 50-79 years not using menopausal hormone therapy, and 4,867 participants of the BMD sub-study.InterventionsNone.Main outcome measuresWe measured baseline VMS, incident adjudicated fractures, and BMD (baseline, annual visits 1, 3, 6, and 9).ResultsAfter adjustment for baseline age, body mass index, race/ethnicity, smoking, and education, the hazard ratio for hip fracture among women with baseline moderate/severe VMS (vs no VMS) was 1.78 (95% confidence interval [CI], 1.20-2.64; P = .01). There was no association between VMS and vertebral fracture. VMS severity was inversely associated with BMD during followup (P = .004 for femoral neck, P = .045 for lumbar spine). In repeated measures models, compared with women who reported no VMS, women with moderate/severe VMS had 0.015 g/cm(2) lower femoral neck BMD (95% CI, -0.025--0.005) and 0.016 g/cm(2) lower lumbar spine BMD (95% CI, -0.032--0.004).ConclusionsWomen with moderate/severe VMS have lower BMD and increased hip fracture rates. Elucidation of the biological mechanisms underlying these associations may inform the design of preventive strategies for at-risk women prior to occurrence of fracture.

ContextSeveral fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired.ObjectiveThe objective of the study was to improve model discrimination by developing a 5-year composite fracture prediction model for fracture sites that display similar risk profiles.DesignThis was a prospective, observational cohort study.SettingThe study was conducted at primary care practices in 10 countries.PatientsWomen aged 55 years or older participated in the study.InterventionSelf-administered questionnaires collected data on patient characteristics, fracture risk factors, and previous fractures.Main outcome measureThe main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age.ResultsOf four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index of 0.75, 47 066 women), and lowest for Fracture Risk Assessment Tool (FRAX) major fracture and a 10-site model (c indices of 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 years of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 years of age from a 10% decrease to a 60% increase.ConclusionsAfter examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.