Associations of Menopausal Vasomotor Symptoms with Fracture Incidence

Context: Vasomotor symptoms (VMS) are common. Whether VMS are associated with fracture incidence or bone mineral density (BMD) levels is unknown. Objective: This study aimed to examine associations of baseline VMS with fracture incidence and BMD. Design: This was a prospective observational study with mean (SD) followup of 8.2 (1.7) years (1993–2005). Setting: Forty United States clinical centers. Participants: We 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. Interventions: None. Main Outcome Measures: We measured baseline VMS, incident adjudicated fractures, and BMD (baseline, annual visits 1, 3, 6, and 9). Results: After 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/cm2 lower femoral neck BMD (95% CI, −0.025–−0.005) and 0.016 g/cm2 lower lumbar spine BMD (95% CI, −0.032–−0.004). Conclusions: Women 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.