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Functional Impairments Mediate Association Between Clinical Fracture Risk and Type 2 Diabetes Mellitus in Older Women.

ABSTRACT: To examine the effect of functional impairments in older women with diabetes mellitus (DM) on incident clinical fractures.Secondary analysis of two large prospective cohort studies.North Carolina Established Populations for Epidemiologic Studies of the Elderly (EPESE) and Women's Health Initiative (WHI) clinical trials.EPESE included 2,704 community-dwelling women aged 65 and older; WHI clinical trials included 68,125 postmenopausal women.Women with DM at baseline were compared with women without in successive Cox proportional hazards models. Functional limitations were determined according to self-reported difficulties with activities of daily living (ADLs) and physical activities.The risk of any clinical fracture during the study period was greater in women with DM, after controlling for age, race and ethnicity, and body mass index, in the EPESE (hazard ratio (HR) = 1.36, 95% confidence interval (CI) = 1.08-1.72) and WHI (HR = 1.29, 95% CI = 1.19-1.39) cohorts. After inclusion of functional limitations, the greater risk of fracture associated with DM decreased in the EPESE (HR = 1.25, 95% CI = 0.98-1.59) and WHI (HR = 1.21, 95% CI = 1.12-1.31) cohorts. In participants with DM, difficulties with moderate physical activities, such as bending or stooping, walking several blocks, and heavy housework, were significantly associated with incident fracture (P < .05).Older women with DM are at greater risk of clinical fractures than those without, independent of bone mineral density. Greater functional impairment in moderate physical activities mediates this greater fracture risk in part, although there remains an unexplained residual DM-associated risk for fracture.

SUBMITTER: Lee RH

PROVIDER: S-EPMC4729209 | biostudies-other | 2015 Aug

REPOSITORIES: biostudies-other

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Functional Impairments Mediate Association Between Clinical Fracture Risk and Type 2 Diabetes Mellitus in Older Women.

Lee Richard H RH Pieper Carl F CF Colón-Emeric Cathleen C

Journal of the American Geriatrics Society 20150722 8

<h4>Objectives</h4>To examine the effect of functional impairments in older women with diabetes mellitus (DM) on incident clinical fractures.<h4>Design</h4>Secondary analysis of two large prospective cohort studies.<h4>Setting</h4>North Carolina Established Populations for Epidemiologic Studies of the Elderly (EPESE) and Women's Health Initiative (WHI) clinical trials.<h4>Participants</h4>EPESE included 2,704 community-dwelling women aged 65 and older; WHI clinical trials included 68,125 postmen ...[more]

PMID: 26201005

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Project description:ImportanceThe reasons for the increased fracture risk in type 2 diabetes (T2D) are not fully understood.ObjectiveTo determine if poorer skeletal characteristics or worse physical function explain the increased fracture risk in T2D.Design, setting, and participantsThis prospective observational study is based on the population-based Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures study cohort of older women, performed in the Gothenburg area between March 2013 and May 2016. Follow-up of incident fracture data was completed in March 2023. Data analysis was performed between June and December 2023.ExposuresData were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using bone densitometry (dual-energy x-ray absorptiometry), and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess bone material strength index (BMSi).Main outcomes and measuresBaseline assessment of bone characteristics and physical function and radiograph verified incident fractures.ResultsOf 3008 women aged 75 to 80 years, 294 women with T2D (mean [SD] age, 77.8 [1.7] years) were compared with 2714 women without diabetes (mean [SD] age, 77.8 [1.6] years). Women with T2D had higher bone mineral density (BMD) at all sites (total hip, 4.4% higher; femoral neck (FN), 4.9% higher; and lumbar spine, 5.2% higher) than women without. At the tibia, women with T2D had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction. There was no difference in BMSi (T2D mean [SD], 78.0 [8.3] vs controls, 78.1 [7.3]). Women with T2D had lower performance on all physical function tests. The study found 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes. During a median (IQR) follow-up of 7.3 (4.4-8.4) years, 1071 incident fractures, 853 major osteoporotic fractures (MOF), and 232 hip fractures occurred. In adjusted (for age, body mass index, clinical risk factors, and FN BMD) Cox regression models, T2D was associated with an increased risk of any fracture (HR, 1.26; 95% CI, 1.04-1.54) and MOF (HR, 1.25; 95% CI, 1.00-1.56).Conclusions and relevanceIn this cohort study of older women, T2D was associated with higher BMD, better bone microarchitecture, and no different BMSi but poorer physical function, suggesting that poor physical function is the main reason for the increased fracture risk in T2D women.

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.

Project description: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.

Project description:ImportanceWhether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are associated with an increased risk of fractures in older adults with type 2 diabetes (T2D) outside of clinical trials remains unknown.ObjectiveTo examine the association of incident fracture among older adults with T2D with initiating an SGLT-2i compared with initiating a dipeptidyl peptidase 4 inhibitor (DPP-4i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA).Design, setting, and participantsThis is a population-based, new-user cohort study including older adults (aged ≥65 years) with T2D enrolled in Medicare fee-for-service from April 2013 to December 2017. Data analysis was performed from October 2020 to April 2021.ExposuresNew users of an SGLT-2i, DPP-4i, or GLP-1RA without a previous fracture were matched in a 1:1:1 ratio using 3-way propensity score matching.Main outcomes and measuresThe primary outcome was a composite end point of nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention within 30 days. After 3-way 1:1:1 propensity score matching, multivariable Cox proportional hazards regression models were used to generate hazard ratios (HRs) for SGLT-2i compared with DPP-4i and GLP-1RA and Kaplan-Meier curves to visualize fracture risk over time across groups.ResultsOf 466 933 new initiators of study drugs, 62 454 patients were new SGLT-2i users. After 3-way matching, 45 889 (73%) new SGLT-2i users were matched to new users of DPP-4i and GLP-1RA, yielding a cohort of 137 667 patients (mean [SD] age, 72 [5] years; 64 126 men [47%]) matched 1:1:1 for analyses. There was no difference in the risk of fracture in SGLT-2i users compared with DPP-4i users (HR, 0.90; 95% CI, 0.73-1.11) or GLP-1RA users (HR, 1.00; 95% CI, 0.80-1.25). Results were consistent across categories of sex, frailty (nonfrail, prefrail, and frail), age (<75 and ≥75 years), and insulin use (baseline users and nonusers).Conclusions and relevanceIn this nationwide Medicare cohort, initiating an SGLT-2i was not associated with an increased risk of fracture in older adults with T2D compared with initiating a DPP-4i or GLP-1RA, with consistent results across categories of frailty, age, and insulin use. These findings add to the evidence base evaluating the potential risks associated with SGLT-2i use for older adults outside of randomized clinical trials.

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Functional Impairments Mediate Association Between Clinical Fracture Risk and Type 2 Diabetes Mellitus in Older Women.

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Functional Impairments Mediate Association Between Clinical Fracture Risk and Type 2 Diabetes Mellitus in Older Women.

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