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UNLABELLED: Patients with cognitive impairment (CI) often do not receive secondary fracture prevention. Use of zoledronic acid led to a similar reduction in re-fracture risk but the survival benefit was limited to those without CI. INTRODUCTION: We tested whether the effects of zoledronic acid (Zol) on re-fracture and mortality differed in patients presenting with a hip fracture by cognitive status. METHODS: We used data from the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial, of yearly intravenous 5 mg Zol vs. placebo in patients presenting with a hip fracture. Primary outcome was new fracture and secondary outcome mortality. Short Portable Mental Status Questionnaire (SPMSQ) with a cut-point of >2 was used to identify CI. Fine-Gray models for competing events were fitted to study the effect of Zol on re-fracture and Cox regression for death. A multiplicative term was introduced to study a potential interaction between treatment and cognitive status on outcomes. RESULTS: Baseline SPMSQ of 1,966/2,127 (92.4%) patients was measured. Three hundred fifty (17.8%) had CI, balanced between treatment arms. In the placebo arm, there was similar fracture incidence between those with and without CI (15.4 vs. 12.3%, p = 0.26). There was no significant interaction for the effect of CI on Zol and re-fracture (p = 0.66). CI was associated with higher 1-year mortality (12.6 vs. 4.3%, p < 0.001) and the interaction was bordering significance (interaction, p = 0.066). Zol prolonged survival only in patients with normal cognitive status [HR 0.56 (95% CI 0.40-0.80)] and not in those with CI [HR 0.90 (95% CI 0.59-1.38)]. CONCLUSIONS: While these results require confirmation, the findings support the use of bisphosphonates in patients with osteoporotic fracture and CI expected to live for more than 6 months.

Original publication




Journal article


Osteoporos int

Publication Date





77 - 83


Aged, Aged, 80 and over, Bone Density Conservation Agents, Cognition Disorders, Diphosphonates, Double-Blind Method, Female, Follow-Up Studies, Hip Fractures, Humans, Imidazoles, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Osteoporosis, Osteoporotic Fractures, Psychiatric Status Rating Scales, Secondary Prevention, Treatment Outcome, Zoledronic Acid