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Impact of Competing Risk of Mortality on Association of Cognitive Impairment With Risk of Hip Fracture in Older Women.

ABSTRACT: Previous studies examining the association of cognitive impairment and dementia with fracture outcomes in older adults have usually used standard approaches that did not take into account the competing risk of mortality. However, ignoring mortality may not provide accurate estimates of risk of fracture because dementia in older adults strongly predicts death, making mortality a competing risk. A total of 1491 women (mean age 87.6 years) participating in the prospective Study of Osteoporotic Fractures (SOF) Year 20 exam were cognitively assessed and followed to ascertain vital status (deaths verified by death certificates) and hip fractures (confirmed by radiographic reports). Cognitive status was categorized as normal, mild cognitive impairment (MCI), or dementia, based on a standardized evaluation. Absolute probability of hip fracture by category of cognitive function was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of hip fracture by cognitive function category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average follow-up of 5.6 years, 139 (9.3%) women experienced a hip fracture and 990 (66.4%) died before experiencing this outcome. Among women with dementia, the risk of hip fracture was 11.7% (95% confidence interval [CI] 7.3-17.2) at 5 years and 18.6% (95% CI 9.1-30.9) at 10 years using traditional survival analysis versus 7.9% (95% CI 5.1-11.6) at 5 years and 8.8% (95% CI 5.8-12.8) at 9.8 years using a competing risk approach. Results were similar for women with MCI. Women with MCI and dementia have a higher risk of hip fractures than women with normal cognition. However, not taking into account the competing risk of mortality significantly overestimates the risk of hip fracture in women in the ninth and tenth decades of life with cognitive impairment. © 2018 American Society for Bone and Mineral Research.

SUBMITTER: Diem SJ

PROVIDER: S-EPMC6136425 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Impact of Competing Risk of Mortality on Association of Cognitive Impairment With Risk of Hip Fracture in Older Women.

Diem Susan J SJ Vo Tien N TN Langsetmo Lisa L Schousboe John T JT Yaffe Kristine K Ensrud Kristine E KE

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20180901 9

Previous studies examining the association of cognitive impairment and dementia with fracture outcomes in older adults have usually used standard approaches that did not take into account the competing risk of mortality. However, ignoring mortality may not provide accurate estimates of risk of fracture because dementia in older adults strongly predicts death, making mortality a competing risk. A total of 1491 women (mean age 87.6 years) participating in the prospective Study of Osteoporotic Frac ...[more]

PMID: 29734471

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Project description:ImportanceClinical trials have demonstrated the antifracture efficacy of bisphosphonate drugs for the first 3 to 5 years of therapy. However, the efficacy of continuing bisphosphonate for as long as 10 years is uncertain.ObjectiveTo examine the association of discontinuing bisphosphonate at study entry, discontinuing at 2 years, and continuing for 5 additional years with the risk of hip fracture among women who had completed 5 years of bisphosphonate treatment at study entry.Design, setting, and participantsThis cohort study included women who were members of Kaiser Permanente Northern and Southern California, 2 integrated health care delivery systems, and who had initiated oral bisphosphonate and completed 5 years of treatment by January 1, 2002, to September 30, 2014. Data analysis was conducted from January 2018 to August 2020.ExposureDiscontinuation of bisphosphonate at study entry (within a 6-month grace period), discontinuation at 2 years (within a 6-month grace period), and continuation for 5 additional years.Main outcomes and measuresThe outcome was hip fracture determined by principal hospital discharge diagnoses. Demographic, clinical, and pharmacological data were ascertained from electronic health records.ResultsAmong 29 685 women (median [interquartile range] age, 71 [64-77] years; 17 778 [60%] non-Hispanic White individuals), 507 incident hip fractures were identified. Compared with bisphosphonate discontinuation at study entry, there were no differences in the cumulative incidence (ie, risk) of hip fracture if women remained on therapy for 2 additional years (5-year risk difference [RD], -2.2 per 1000 individuals; 95% CI, -20.3 to 15.9 per 1000 individuals) or if women continued therapy for 5 additional years (5-year RD, 3.8 per 1000 individuals; 95% CI, -7.4 to 15.0 per 1000 individuals). While 5-year differences in hip fracture risk comparing continuation for 5 additional years with discontinuation at 2 additional years were not statistically significant (5-year RD, 6.0 per 1000 individuals; 95% CI, -9.9 to 22.0 per 1000 individuals), interim hip fracture risk appeared lower if women discontinued after 2 additional years (3-year RD, 2.8 per 1000 individuals; 95% CI, 1.3 to 4.3 per 1000 individuals; 4-year RD, 9.3 per 1000 individuals; 95% CI, 6.3 to 12.3 per 1000 individuals) but not without a 6-month grace period to define discontinuation.Conclusions and relevanceIn this study of women treated with bisphosphonate for 5 years, hip fracture risk did not differ if they discontinued treatment compared with continuing treatment for 5 additional years. If women continued for 2 additional years and then discontinued, their risk appeared lower than continuing for 5 additional years. Discontinuation at other times and fracture rates during intervening years should be further studied.

Project description:Among 377,561 female Medicare beneficiaries who sustained a fracture, 10% had another fracture within 1 year, 18% within 2 years, and 31% within 5 years. Timely management to reduce risk of subsequent fracture is warranted following all nontraumatic fractures, including nonhip nonvertebral fractures, in older women.IntroductionPrior fracture is a strong predictor of subsequent fracture; however, postfracture treatment rates are low. Quantifying imminent (12-24 month) risk of subsequent fracture in older women may clarify the need for early postfracture management.MethodsThis retrospective cohort study used Medicare administrative claims data. Women ≥ 65 years who sustained a clinical fracture (clinical vertebral and nonvertebral fracture; index date) and were continuously enrolled for 1-year pre-index and ≥ 1-year (≥ 2 or ≥ 5 years for outcomes at those time points) post-index were included. Cumulative incidence of subsequent fracture was calculated from 30 days post-index to 1, 2, and 5 years post-index. For appendicular fractures, only those requiring hospitalization or surgical repair were counted. Death was considered a competing risk.ResultsAmong 377,561 women (210,621 and 10,969 for 2- and 5-year outcomes), cumulative risk of subsequent fracture was 10%, 18%, and 31% at 1, 2, and 5 years post-index, respectively. Among women age 65-74 years with initial clinical vertebral, hip, pelvis, femur, or clavicle fractures and all women ≥ 75 years regardless of initial fracture site (except ankle and tibia/fibula), 7-14% fractured again within 1 year depending on initial fracture site; risk rose to 15-26% within 2 years and 28-42% within 5 years. Risk of subsequent hip fracture exceeded 3% within 5 years in all women studied, except those < 75 years with an initial tibia/fibula or ankle fracture.ConclusionsWe observed a high and early risk of subsequent fracture following a broad array of initial fractures. Timely management with consideration of pharmacotherapy is warranted in older women following all fracture types evaluated.

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Impact of Competing Risk of Mortality on Association of Cognitive Impairment With Risk of Hip Fracture in Older Women.

Publications

Impact of Competing Risk of Mortality on Association of Cognitive Impairment With Risk of Hip Fracture in Older Women.

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