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ABSTRACT: OBJECTIVES: To determine which older adults tend to receive potentially inappropriate medications (PIMs), how this may differ according to cognitive status, and how the trajectories of PIM use change over time. DESIGN: Ten-year longitudinal cohort study. SETTING: Three clinical sites in the United States. PARTICIPANTS: One thousand four hundred eighty-four community-dwelling women aged 75 and older. MEASUREMENTS: At follow-up, cognitive status was ascertained and classified as normal, mild cognitive impairment (MCI), or dementia. Beers 2003 criteria and other literature were used to identify PIMs from detailed medication inventory performed at three time points. Anticholinergic load was measured using the Anticholinergic Cognitive Burden Scale (ACB), which assigns medications a value from 0 to 3 depending on anticholinergic properties. RESULTS: At baseline, 23.9% of women were taking at least one PIM and the mean ± SD ACB score was 1.41 ± 1.69. The most frequently reported PIMs were anticholinergics (15.2%), benzodiazepines (8.6%), and antispasmodics (8.0%). Over 10 years, PIM use increased for women with dementia (24.9-33.1%; P = .02) but remained fairly constant for women with MCI (23.9-23.0%; P = .84) and normal cognitive status (22.2-19.8%; P = .17). Mean ACB score increased significantly (P < .001) over time for all groups (dementia: 1.28-2.05; MCI: 0.98-1.66; normal: 0.99-1.48). CONCLUSION: PIM use and anticholinergic load in a community-dwelling population of older women was high, especially in women who later developed dementia. Future guidelines should limit PIM use and seek safer alternatives.
Journal of the American Geriatrics Society 01/2013; · 3.74 Impact Factor
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ABSTRACT: To test the hypothesis that older women with higher cystatin C are at increased risk of hip fracture independent of traditional risk factors including hip bone mineral density (BMD), we performed a case-cohort analysis nested in a cohort of 4709 white women attending a Year 10 (1997-1998) examination of the Study of Osteoporotic Fractures that included a random sample of 1170 women and the first 300 women with incident hip fracture occurring after Year 10 examination. Serum cystatin C and creatinine were measured in Year 10 sera. In a model adjusted for age, clinical site, body mass index and total hip BMD, higher cystatin C was associated with an increased risk of hip fracture (p for linear trend 0.008) with women in quartile 4 having a 1.9-fold higher risk (hazard ratio (HR) 1.91, 95% confidence (CI) 1.24-2.95) compared with those in quartile 1 (referent group). Further adjustment for additional risk factors only slightly attenuated the association; the risk for hip fracture was 1.7-fold (HR 1.74, 95% CI 1.11-2.72) higher in women in quartile 4 compared with those in quartile 1. In contrast, neither serum creatinine nor creatinine-based estimated glomerular filtration rate (eGFR(Cr) ) were associated with risk of hip fracture. Older women with higher cystatin C, but not higher serum creatinine or lower eGFR(Cr) , have an increased risk of hip fracture independent of traditional risk factors. These findings suggest that cystatin C may be a promising biomarker for identification of older adults at high risk of hip fracture. © 2013 American Society for Bone and Mineral Research.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2013; · 6.04 Impact Factor
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Amy L Byers,
Eric Vittinghoff,
Li-Yung Lui,
Tina Hoang,
Dan G Blazer,
Kenneth E Covinsky,
Kristine E Ensrud,
Jane A Cauley, Teresa A Hillier,
Lisa Fredman,
Kristine Yaffe
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ABSTRACT: CONTEXT Despite the frequent occurrence of depressive symptoms among older adults, especially women, little is known about the long-term course of late-life depressive symptoms. OBJECTIVE To characterize the natural course of depressive symptoms among older women (from the young old to the oldest old) followed up for almost 20 years. DESIGN Using latent-class growth-curve analysis, we analyzed women enrolled in an ongoing prospective cohort study (1988 through 2009). SETTING Clinic sites in Baltimore, Maryland; Minneapolis, Minnesota; the Monongahela Valley near Pittsburgh, Pennsylvania; and Portland, Oregon. PARTICIPANTS We studied 7240 community-dwelling women 65 years or older. MAIN OUTCOME MEASURE The Geriatric Depression Scale short form (score range, 0-15) was used to routinely assess depressive symptoms during the follow-up period. RESULTS Among older women, we identified 4 latent classes during 20 years, with the predicted probabilities of group membership totaling 27.8% with minimal depressive symptoms, 54.0% with persistently low depressive symptoms, 14.8% with increasing depressive symptoms, and 3.4% with persistently high depressive symptoms. In an adjusted model for latent class membership, odds ratios (ORs) for belonging in the increasing depressive symptoms and persistently high depressive symptoms classes, respectively, compared with a group having minimal depressive symptoms were substantially and significantly (P < .05) elevated for the following variables: baseline smoking (ORs, 4.69 and 7.97), physical inactivity (ORs, 2.11 and 2.78), small social network (ORs, 3.24 and 6.75), physical impairment (ORs, 8.11 and 16.43), myocardial infarction (ORs, 2.09 and 2.41), diabetes mellitus (ORs, 2.98 and 3.03), and obesity (ORs, 1.86 and 2.90). CONCLUSIONS During 20 years, almost 20% of older women experienced persistently high depressive symptoms or increasing depressive symptoms. In addition, these women had more comorbidities, physical impairment, and negative lifestyle factors at baseline. These associations support the need for intervention and prevention strategies to reduce depressive symptoms into the oldest-old years.
Archives of general psychiatry 10/2012; 69(10):1073-9. · 12.26 Impact Factor
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ABSTRACT: To determine whether objectively measured sleep quality predicts 5-year incident instrumental activity of daily living (IADL) impairment and decline in grip strength and gait speed in older women.
Prospective cohort.
Participants' homes, Study of Osteoporotic Fractures sites.
Eight hundred seventeen women with a mean age of 82.4 at baseline.
Participants completed 4.1 ± 0.7 nights of wrist actigraphy at baseline and measures of IADL impairment, grip strength, and gait speed at baseline and 5-year follow-up.
After 5 years of follow-up, approximately 41% of participants had incident impairment in one or more IADLs. The quartile of women with the shortest total sleep time (TST) had 93% greater odds of incident IADL impairment than the longest sleepers (adjusted odds ratio (AOR) = 1.93, 95% confidence interval (CI) = 1.25-2.97). Similarly, the quartile of women with the lowest sleep efficiency (SE) had 65% greater odds of impairment than those with the highest (AOR = 1.65, 95% CI = 1.06-2.57). Women in the shortest TST quartile had twice the odds of declining grip strength as those with the longest TST (AOR = 1.97, 95% CI = 1.17-3.32). Finally, women in the quartiles with the most wake after sleep onset (WASO) and the lowest SE had approximately 90% greater odds of grip strength decline than those with the least WASO (AOR = 1.90, 95% CI = 1.11-3.24) and SE (AOR = 1.92, 95% CI = 1.12-3.29).
Findings indicate that shorter sleep duration, greater WASO, and lower SE are risk factors for functional or physical decline in older women.
Journal of the American Geriatrics Society 06/2012; 60(6):1092-8. · 3.74 Impact Factor
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Kimberly K Vesco,
Lynn M Marshall,
Heidi D Nelson,
Linda Humphrey,
Joanne Rizzo,
Kathryn L Pedula,
Jane A Cauley,
Kristine E Ensrud,
Marc C Hochberg,
Diana Antoniucci, Teresa A Hillier
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ABSTRACT: The aim of this study was to determine whether older postmenopausal women with a history of bilateral oophorectomy before natural menopause (surgical menopause) have a higher risk of nonvertebral postmenopausal fracture than women with natural menopause.
We used 21 years of prospectively collected incident fracture data from the ongoing Study of Osteoporotic Fractures, a cohort study of community-dwelling women without previous bilateral hip fracture who were 65 years or older at enrollment, to determine the risk of hip, wrist, and any nonvertebral fracture. χ(2) and t tests were used to compare the two groups on important characteristics. Multivariable Cox proportional hazards regression models stratified by baseline oral estrogen use status were used to estimate the risk of fracture.
Baseline characteristics differed significantly among the 6,616 women within the Study of Osteoporotic Fractures who underwent either surgical (1,157) or natural (5,459) menopause, including mean age at menopause (44.3 ± 7.4 vs 48.9 ± 4.9 y, P < 0.001) and current use of oral estrogen (30.2% vs 6.5%, P < 0.001). Fracture rates were not significantly increased for surgical versus natural menopause, even among women who had never used oral estrogen (hip fracture: hazard ratio [HR], 0.87; 95% CI, 0.63-1.21; wrist fracture: HR, 1.10; 95% CI, 0.78-1.57; any nonvertebral fracture: HR, 1.11; 95% CI, 0.93-1.32).
These data provide some reassurance that the long-term risk of nonvertebral fracture is not substantially increased for postmenopausal women who experienced premenopausal bilateral oophorectomy, compared with postmenopausal women with intact ovaries, even in the absence of postmenopausal estrogen therapy.
Menopause (New York, N.Y.) 05/2012; 19(5):510-6. · 3.08 Impact Factor
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ABSTRACT: Use of antidepressant medications has been associated with increased risk of fracture, but prior studies have been limited
by incomplete control of confounders or a limited number of fractures. Use of antidepressant medications by 8,217 community-dwelling
women aged 69 and older from a population-based prospective cohort study at four US clinical centers was assessed by interview
at four examinations over a 10-year period, beginning in 1992–1994. Use was coded as a time-dependent variable. Incident fractures
occurring after the initial medication assessment until July 2007 were confirmed by radiographic reports. Potential confounders
were included in multivariable models and updated at each follow-up visit. Compared to nonusers of antidepressant medications,
women using SSRIs experienced a higher risk of nonspine fracture in age-adjusted models (HR=1.36, 95% CI 1.11–1.67) and
in multivariable models controlling for potential confounders (HR=1.30, 95% CI 1.04–1.62). SSRI use was not associated with
an increased risk of first hip fracture (HR=1.01, 95% CI 0.71–1.44) but was associated with an increased risk of wrist fracture
(HR=1.54, 95% CI 1.01–2.36). TCA use was associated with an increased risk of nonspine fracture in age-adjusted models,
but in multivariable models this risk was attenuated. SSRI use was associated with a higher risk of any nonspine fracture,
but not hip fracture, in this cohort of older women. TCA use was associated with a higher risk of nonspine fracture, but this
association was in part explained by confounding factors.
KeywordsSelective serotonin reuptake inhibitor–Tricyclic antidepressant–Antidepressant–Fracture–Population study–Depression
Calcified Tissue International 04/2012; 88(6):476-484. · 2.38 Impact Factor
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Gregory J. Tranah,
Brent C. Taylor,
Li-Yung Lui,
Joseph M. Zmuda,
Jane A. Cauley,
Kristine E. Ensrud, Teresa A. Hillier,
Marc C. Hochberg,
Jia Li,
Brian K. Rhees,
Henry A. Erlich,
Mark D. Sternlicht,
Gary Peltz,
Steven R. Cummings,
For the Study of Osteoporotic Fractures (SOF) Research Group
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ABSTRACT: Candidate osteoporosis gene variants were examined for associations with fracture risk and bone mineral density (BMD). A total
of 9704 white women were recruited at four U.S. clinical centers and enrolled into the Study of Osteoporotic Fractures, a
longitudinal cohort study. Genotyping of 31 polymorphisms from 18 candidate osteoporosis genes was performed in 6752 women.
Incident radiographic fractures were identified at the third and eighth examinations compared with the baseline examination.
BMD was measured at the total hip by dual-energy X-ray absorptiometry. Analyses were adjusted for age, clinic site, and self-reported
ethnicity. During a mean follow-up of 14.5years, a total of 849 hip, 658 vertebral, and 2496 nonhip/nonvertebral fractures
occurred in 6752 women. Women carrying the ALOX15_G48924T T/T genotype had a higher rate of hip fracture (hazard ratio [HR]=1.33;95%
confidence interval [95% CI]=1.00–1.77) compared with the G/G genotype. Compared with those carrying the PRL_T228C T/T genotype,
women with either the C/C (HR=0.80; 95% CI=0.67–0.95) or C/T (HR=0.81; 95% CI=0.68–0.97) genotype had a lower rate
of nonvertebral/nonhip fractures. Women carrying the BMP2_A125611G G/G genotype had a higher rate of vertebral fracture (odds
ratio [OR]=1.51; 95% CI=1.03–2.23) compared with the A/A genotype. Women with the ESR1_C1335G G/G genotype had a higher
rate of vertebral fracture (OR=1.64; 95% CI=1.07–2.50) compared with the C/C genotype. Compared with those with the MMP2_C595T
C/C genotype, women with the C/T (OR=0.79; 95% CI=0.65–0.96) or T/T (OR=0.44; 95% CI=0.27–0.72) genotype had a lower
rate of vertebral fracture. In conclusion, polymorphisms in several candidate genes were associated with hip, vertebral, and
nonhip/nonvertebral fractures but not with total hip BMD in this large population based cohort study.
Calcified Tissue International 04/2012; 83(3):155-166. · 2.38 Impact Factor
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ABSTRACT: To evaluate sleep quality in women with hip pain due to daily activities involving the lower extremity joints.
We evaluated the association of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) hip pain severity score with objective sleep measures obtained by wrist actigraphy in 2,225 white women ≥ 65 years of age enrolled in the Study of Osteoporotic Fractures.
Women had an increased odds of spending ≥ 90 minutes awake after sleep onset (odds ratio [OR] 1.28, 95% confidence interval [95% CI] 1.11-1.50) for every 5-point increase in hip pain score after adjustment for all covariates. Hip pain when sitting or lying was the strongest predictor of sleep fragmentation (OR 2.0, 95% CI 1.47-2.73); however, standing pain was associated with a higher number of awake minutes in bed scored from sleep onset to the end of the last sleep episode, independent of pain while in bed (OR 1.41, 95% CI 1.07-2.01). Sleep disturbances increased significantly after the first 2 hours of sleep in women with severe hip pain compared to those without hip pain (mean ± SD 1.4 ± 0.47 minutes per hour of sleep; P < 0.003). Similar associations were observed for long wake episodes >5 minutes. There were no associations between daytime napping, sleep latency, sleep efficiency, and total sleep minutes and WOMAC hip pain.
Fragmented sleep was greater in women with hip pain compared to those without hip pain; however, fragmented sleep in women with severe hip pain compared to those without hip pain was unchanged until after the first 2 hours of sleep. Further investigations into pain medications wearing off over time or the prolonged periods of inactivity decreasing the pain threshold are warranted.
Arthritis care & research. 02/2012; 64(7):1070-8.
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Teresa A Hillier,
Li-Yung Lui,
Deborah M Kado,
Es Leblanc,
Kimberly K Vesco,
Douglas C Bauer,
Jane A Cauley,
Kristine E Ensrud,
Dennis M Black,
Marc C Hochberg,
Steven R Cummings
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ABSTRACT: We examined if height loss in older women predicts risk of hip fractures, other non-spine fractures, and mortality, and whether this risk is independent of both vertebral fractures (VFx) and bone mineral density (BMD) by dual-energy x-ray absorptiometry. Among 3,124 women age 65 and older in the Study of Osteoporotic Fractures, we assessed the association with measured height change between Year 0 (1986-1988) and Year 15 (2002-2004) and subsequent risk of radiologically confirmed hip fractures, other non-spine fractures, and mortality assessed via death certificates. Follow-up occurred every 4 months for fractures and vital status (>95% contacts complete). Cox proportional hazards models assessed risk of hip fracture, non-spine fracture, and mortality over a mean of 5 years after height change was assessed (i.e, after final height measurement). After adjustment for VFx, BMD and other potential covariates, height loss >5 cm was associated with a marked increased risk of hip fracture (HR 1.50, 95% CI 1.06, 2.12), non-spine fracture (HR 1.48; 95% CI 1.20, 1.83), and mortality (1.45; 95% CI 1.21, 1.73). Although primary analyses were a subset of 3,124 survivors healthy enough to return for a Year 15 height measurement, a sensitivity analysis in the entire cohort (n = 9,677) using initial height in earlier adulthood (self-reported height at age 25 [-40 years] to measured height age >65 years [Year 0]) demonstrated consistent results. Height loss >5 cm (2″) in older women was associated with a nearly 50% increased risk of hip fracture, non-spine fracture, and mortality-independent of incident VFx and BMD. © 2011 American Society for Bone and Mineral Research.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 11/2011; · 6.04 Impact Factor
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Gregory J Tranah,
Terri Blackwell,
Katie L Stone,
Sonia Ancoli-Israel,
Misti L Paudel,
Kristine E Ensrud,
Jane A Cauley,
Susan Redline, Teresa A Hillier,
Steven R Cummings,
Kristine Yaffe
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ABSTRACT: Previous cross-sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community-dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI).
Activity rhythm data were collected from 1,282 healthy community-dwelling women from the Study of Osteoporotic Fractures (SOF) cohort (mean age 83 years) with wrist actigraphy for a minimum of three 24-hour periods. Each participant completed a neuropsychological test battery and had clinical cognitive status (dementia, MCI, normal) adjudicated by an expert panel approximately 5 years later. All analyses were adjusted for demographics, body mass index (BMI), functional status, depression, medications, alcohol, caffeine, smoking, health status, and comorbidities.
After 4.9 years of follow-up, 195 (15%) women had developed dementia and 302 (24%) had developed MCI. Older women with decreased activity rhythms had a higher likelihood of developing dementia or MCI when comparing those in the lowest quartiles of amplitude (odds ratio [OR] = 1.57; 95% CI, 1.09-2.25) or rhythm robustness (OR = 1.57; 95% CI, 1.10-2.26) to women in the highest quartiles. An increased risk of dementia or MCI (OR = 1.83; 95% CI, 1.29-2.61) was found for women whose timing of peak activity occurred later in the day (after 3:51 PM) when compared to those with average timing (1:34 PM-3:51 PM).
Older, healthy women with decreased circadian activity rhythm amplitude and robustness, and delayed rhythms have increased odds of developing dementia and MCI. If confirmed, future studies should examine whether interventions (physical activity, bright light exposure) that influence activity rhythms will reduce the risk of cognitive deterioration in the elderly.
Annals of Neurology 11/2011; 70(5):722-32. · 11.09 Impact Factor
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Erin S LeBlanc, Teresa A Hillier,
Kathryn L Pedula,
Joanne H Rizzo,
Peggy M Cawthon,
Howard A Fink,
Jane A Cauley,
Douglas C Bauer,
Dennis M Black,
Steven R Cummings,
Warren S Browner
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ABSTRACT: Fractures have been associated with subsequent increases in mortality, but it is unknown how long that increase persists.
A total of 5580 women from a large community-based, multicenter US prospective cohort of 9704 (Study of Osteoporotic Fractures) were observed prospectively for almost 20 years. We age-matched 1116 hip fracture cases with 4 control participants (n = 4464). To examine the effect of health status, we examined a healthy older subset (n = 960) 80 years or older who attended the 10-year follow-up examination and reported good or excellent health. Incident hip fractures were adjudicated from radiology reports by study physicians. Death was confirmed by death certificates.
Hip fracture cases had 2-fold increased mortality in the year after fracture compared with controls (16.9% vs 8.4%; multivariable adjusted odds ratio [OR], 2.4; 95% CI, 1.9-3.1]. When examined by age and health status, short-term mortality was increased in those aged 65 to 69 years (16.3% vs 3.7%; OR, 5.0; 95% CI, 2.6-9.5), 70 to 79 years (16.5% vs 8.9%; OR, 2.4; 95% CI, 1.8-3.3), and only in those 80 years or older with good or excellent health (15.1% vs 7.2%; multivariable adjusted OR, 2.8; 95% CI, 1.5-5.2). After the first year, survival of hip fracture cases and controls was similar except in those aged 65 to 69 years, who continued to have increased mortality.
Short-term mortality is increased after hip fracture in women aged 65 to 79 years and in exceptionally healthy women 80 years or older. Women 70 years or older return to previous risk levels after a year. Interventions are needed to decrease mortality in the year after hip fracture, when mortality risk is highest.
Archives of internal medicine 09/2011; 171(20):1831-7. · 11.46 Impact Factor
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ABSTRACT: To understand the relationships between maternal glycemia during pregnancy and prenatal and early postnatal growth by evaluating cord C-peptide and IGF-I as mediating biomarkers in boys and girls separately.
We evaluated 342 neonates within the EDEN mother-child cohort study born to mothers without diabetes diagnosis before pregnancy. We measured maternal glycemia at 24-28 weeks of gestation and neonates' cord blood C-peptide (used as a proxy for fetal insulin) and IGF-I at birth. Reported maternal prepregnancy BMI and all measured infant weights and lengths in the 1st year were recorded. Growth modeling was used to obtain an individual growth curve for each infant in the 1st year. Path models, a type of structural equation modeling, were used for statistical analysis. Path analysis is a multivariate method associated with a graphical display that allows evaluation of mediating factors and distinguishes direct, indirect, and total effects.
Cord C-peptide at birth was positively correlated with maternal prepregnancy BMI and maternal glycemia and was higher in girls. In a path model that represented prenatal growth, there was no significant direct effect of maternal glycemia on birth weight, but the effect of maternal glycemia on birth weight was mediated by fetal insulin and IGF-I in both girls and boys. However, in girls only, higher concentrations of cord C-peptide (but not cord IGF-I or maternal glucose) were associated with slower weight growth in the first 3 months of life.
Our study underlines the role of the fetal insulin-IGF-I axis in the relationship between maternal glycemia during pregnancy and birth weight. We also show for the first time that high insulin concentration in female fetuses is associated with slower early postnatal growth. This slow, early growth pattern may be programmed by fetal hyperinsulinemia, and girls may be more susceptible than boys to its consequences.
Diabetes 06/2011; 60(8):2152-9. · 8.29 Impact Factor
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Ann V Schwartz,
Eric Vittinghoff,
Douglas C Bauer, Teresa A Hillier,
Elsa S Strotmeyer,
Kristine E Ensrud,
Meghan G Donaldson,
Jane A Cauley,
Tamara B Harris,
Annemarie Koster,
Catherine R Womack,
Lisa Palermo,
Dennis M Black
[show abstract]
[hide abstract]
ABSTRACT: Type 2 diabetes mellitus (DM) is associated with higher bone mineral density (BMD) and paradoxically with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in patients with DM.
To determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm (FRAX) score are associated with hip and nonspine fracture risk in older adults with type 2 DM.
Data from 3 prospective observational studies with adjudicated fracture outcomes (Study of Osteoporotic Fractures [December 1998-July 2008]; Osteoporotic Fractures in Men Study [March 2000-March 2009]; and Health, Aging, and Body Composition study [April 1997-June 2007]) were analyzed in older community-dwelling adults (9449 women and 7436 men) in the United States.
Self-reported incident fractures, which were verified by radiology reports.
Of 770 women with DM, 84 experienced a hip fracture and 262 a nonspine fracture during a mean (SD) follow-up of 12.6 (5.3) years. Of 1199 men with DM, 32 experienced a hip fracture and 133 a nonspine fracture during a mean (SD) follow-up of 7.5 (2.0) years. Age-adjusted hazard ratios (HRs) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 (95% confidence interval [CI], 1.43-2.48) for hip fracture and 1.52 (95% CI, 1.31-1.75) for nonspine fracture, and in men with DM were 5.71 (95% CI, 3.42-9.53) for hip fracture and 2.17 (95% CI, 1.75-2.69) for nonspine fracture. The FRAX score was also associated with fracture risk in participants with DM (HRs for 1-unit increase in FRAX hip fracture score, 1.05; 95% CI, 1.03-1.07, for women with DM and 1.16; 95% CI, 1.07-1.27, for men with DM; HRs for 1-unit increase in FRAX osteoporotic fracture score, 1.04; 95% CI, 1.02-1.05, for women with DM and 1.09; 95% CI, 1.04-1.14, for men with DM). However, for a given T score and age or for a given FRAX score, participants with DM had a higher fracture risk than those without DM. For a similar fracture risk, participants with DM had a higher T score than participants without DM. For hip fracture, the estimated mean difference in T score for women was 0.59 (95% CI, 0.31-0.87) and for men was 0.38 (95% CI, 0.09-0.66).
Among older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk; however, in these patients compared with participants without DM, the fracture risk was higher for a given T score and age or for a given FRAX score.
JAMA The Journal of the American Medical Association 06/2011; 305(21):2184-92. · 30.03 Impact Factor
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[show abstract]
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ABSTRACT: Use of antidepressant medications has been associated with increased risk of fracture, but prior studies have been limited by incomplete control of confounders or a limited number of fractures. Use of antidepressant medications by 8,217 community-dwelling women aged 69 and older from a population-based prospective cohort study at four US clinical centers was assessed by interview at four examinations over a 10-year period, beginning in 1992-1994. Use was coded as a time-dependent variable. Incident fractures occurring after the initial medication assessment until July 2007 were confirmed by radiographic reports. Potential confounders were included in multivariable models and updated at each follow-up visit. Compared to nonusers of antidepressant medications, women using SSRIs experienced a higher risk of nonspine fracture in age-adjusted models (HR = 1.36, 95% CI 1.11-1.67) and in multivariable models controlling for potential confounders (HR = 1.30, 95% CI 1.04-1.62). SSRI use was not associated with an increased risk of first hip fracture (HR = 1.01, 95% CI 0.71-1.44) but was associated with an increased risk of wrist fracture (HR = 1.54, 95% CI 1.01-2.36). TCA use was associated with an increased risk of nonspine fracture in age-adjusted models, but in multivariable models this risk was attenuated. SSRI use was associated with a higher risk of any nonspine fracture, but not hip fracture, in this cohort of older women. TCA use was associated with a higher risk of nonspine fracture, but this association was in part explained by confounding factors.
Calcified Tissue International 04/2011; 88(6):476-84. · 2.38 Impact Factor
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Teresa A Hillier,
Jane A Cauley,
Joanne H Rizzo,
Kathryn L Pedula,
Kristine E Ensrud,
Douglas C Bauer,
Li-Yung Lui,
Kimberly K Vesco,
Dennis M Black,
Meghan G Donaldson,
Erin S Leblanc,
Steven R Cummings
[show abstract]
[hide abstract]
ABSTRACT: Bone mineral density (BMD) is a strong predictor of fracture, yet most fractures occur in women without osteoporosis by BMD criteria. To improve fracture risk prediction, the World Health Organization recently developed a country-specific fracture risk index of clinical risk factors (FRAX) that estimates 10-year probabilities of hip and major osteoporotic fracture. Within differing baseline BMD categories, we evaluated 6252 women aged 65 or older in the Study of Osteoporotic Fractures using FRAX 10-year probabilities of hip and major osteoporotic fracture (ie, hip, clinical spine, wrist, and humerus) compared with incidence of fractures over 10 years of follow-up. Overall ability of FRAX to predict fracture risk based on initial BMD T-score categories (normal, low bone mass, and osteoporosis) was evaluated with receiver-operating-characteristic (ROC) analyses using area under the curve (AUC). Over 10 years of follow-up, 368 women incurred a hip fracture, and 1011 a major osteoporotic fracture. Women with low bone mass represented the majority (n = 3791, 61%); they developed many hip (n = 176, 48%) and major osteoporotic fractures (n = 569, 56%). Among women with normal and low bone mass, FRAX (including BMD) was an overall better predictor of hip fracture risk (AUC = 0.78 and 0.70, respectively) than major osteoporotic fractures (AUC = 0.64 and 0.62). Simpler models (eg, age + prior fracture) had similar AUCs to FRAX, including among women for whom primary prevention is sought (no prior fracture or osteoporosis by BMD). The FRAX and simpler models predict 10-year risk of incident hip and major osteoporotic fractures in older US women with normal or low bone mass.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2011; 26(8):1774-82. · 6.04 Impact Factor
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[show abstract]
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ABSTRACT: Vitamin D deficiency and frailty are common with aging, but the association between these conditions is uncertain.
To determine the association between 25-hydroxyvitamin D (25(OH)D) levels and prevalent and incident frailty status among older women.
Cross-sectional and longitudinal analyses of a prospective cohort study.
Four U.S. centers.
6307 women aged≥69 years.
Frailty status classified as robust, intermediate stage, or frail at baseline; and robust, intermediate stage, frail, or dead (all-cause mortality) at follow-up an average of 4.5 years later.
At baseline, there was a U-shaped association between 25(OH)D level and odds of frailty with the lowest risk among women with levels 20.0-29.9 ng/ml (referent group). Compared with this group, the odds of frailty were higher among those with levels<15.0 ng/ml [multivariable odds ratio (MOR) 1.47, 95% confidence interval (CI), 1.19-1.82], those with levels 15.0-19.9 ng/ml (MOR 1.24, 95% CI 0.99-1.54), and those with levels≥30 ng/ml (MOR 1.32, 95% CI 1.06-1.63). Among 4551 nonfrail women at baseline, the odds of frailty/death (vs. robust/intermediate) at follow-up appeared higher among those with levels 15.0-19.9 ng/ml (MOR 1.21, 95% CI 0.99-1.49), but the CI overlapped 1.0. The odds of death (vs. robust/intermediate/frail at follow-up) was higher among those with levels<15.0 ng/ml (MOR 1.40, 95% CI 1.04-1.88) and those with levels 15.0-19.9 ng/ml (MOR 1.30, 95% CI 0.97-1.75), although the latter association did not quite reach significance.
Lower (<20 ng/ml) and higher (≥30 ng/ml) levels of 25(OH)D among older women were moderately associated with a higher odds of frailty at baseline. Among nonfrail women at baseline, lower levels (<20 ng/ml) were modestly associated with an increased risk of incident frailty or death at follow-up.
The Journal of clinical endocrinology and metabolism 12/2010; 95(12):5266-73. · 6.50 Impact Factor
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ABSTRACT: Growth velocity in the first months of postnatal life has been associated with later overweight and obesity.
We analyzed prenatal and postnatal factors in association with weight, length, and growth velocities in the first 3 mo of life.
We estimated weight, length, and instantaneous weight- and length-growth velocities (in g/d and mm/d) in 1418 term infants at 1 and 3 mo of age and evaluated the following potential determinants: maternal prepregnancy body mass index (BMI), 1-h plasma glucose concentrations during pregnancy, smoking, socioeconomic status, parity, paternal BMI, parental heights, and infant feeding, gestational age, and sex.
Maternal obesity and plasma glucose concentrations were associated with the weights and lengths of offspring at birth but not at 1 and 3 mo after birth. In contrast, there was no association between paternal BMI and anthropometric measures of offspring at birth, but by 3 mo of age infants of obese fathers had significantly higher weights and weight-growth velocities than did infants of fathers with a normal BMI. Maternal weight gain was a significant predictor of weight at birth and 3 mo of age. Exclusively breastfed infants had a slower weight-growth velocity as early as 1 mo of age compared with exclusively formula-fed infants.
In the first 3 mo of life, the positive associations between maternal obesity, plasma glucose concentrations, and infant anthropometric measures at birth seem to progressively fade away, whereas the emerging association with paternal BMI may indicate an early postnatal influence of paternal genetics. Among the determinants we evaluated, some are potentially modifiable, such as maternal gestational weight gain and infant feeding. The identification of optimal patterns of growth remains crucial before providing any clinical recommendations.
American Journal of Clinical Nutrition 09/2010; 92(3):594-602. · 6.67 Impact Factor
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ABSTRACT: Chronic stress may lead to health decline through metabolic syndrome. Thus, persons in stressful caregiving situations who also have more indicators of metabolic syndrome may experience more decline than other caregivers or noncaregivers.
The sample included 921 women (338 caregivers and 583 noncaregivers) from the Caregiver-Study of Osteoporotic Fractures study. Participants had home-based baseline and 1-year follow-up interviews between 1999 and 2003. At baseline, caregivers were categorized as long term ((3)4 years) versus short term (<4 years), and caring for someone with Alzheimer's disease/dementia or not. A metabolic risk composite score was the sum of four indicators: body mass index (3)30, and diagnosis or using medications for hypertension, diabetes, or high cholesterol. Walking speed (m/second) was measured at both interviews.
Walking speed declined for the total sample (adjusted mean = -0.005 m/second, +/-0.16) over an average of 1.04 years (+/-0.16). Overall, caregiving was not associated with decline. Increasing metabolic risk score was associated with greater decline for the total sample and long-term and dementia caregivers, but not other caregivers or noncaregivers. Metabolic risk score modified the adjusted associations between years of caregiving and dementia caregiving with walking speed decline (p values for interaction terms were 0.039 and 0.057, respectively). The biggest declines were in long-term caregivers and dementia caregivers who also had 3-4 metabolic indicators (-0.10 m/second and -0.155 m/second, respectively).
Walking speed declined the most among older women who had both stressful caregiving situations and more metabolic syndrome indicators, suggesting these caregiver subgroups may have increased risk of health decline.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 03/2010; 65(5):565-72. · 4.60 Impact Factor
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ABSTRACT: To determine whether circadian activity rhythms are associated with mortality in community-dwelling older women.
Prospective study of mortality.
A cohort study of health and aging.
Three thousand twenty-seven community-dwelling women from the Study of Osteoporotic Fractures cohort (mean age 84).
Activity data were collected using wrist actigraphy for a minimum of three 24-hour periods, and circadian activity rhythms were computed. Parameters of interest included height of activity peak (amplitude), midline estimating statistic of rhythm (mesor), strength of activity rhythm (robustness), and time of peak activity (acrophase). Vital status, with cause of death adjudicated through death certificates, was prospectively ascertained.
Over an average of 4.1 years of follow-up, there were 444 (14.7%) deaths. There was an inverse association between peak activity height and all-cause mortality rates, with higher mortality rates observed in the lowest activity quartile (hazard ratio (HR)=2.18, 95% confidence interval (CI)=1.63-2.92) than in the highest quartile after adjusting for age, clinic site, race, body mass index, cognitive function, exercise, instrumental activity of daily living impairments, depression, medications, alcohol, smoking, self-reported health status, married status, and comorbidities. A greater risk of mortality from all causes was observed for those in the lowest quartiles of mesor (HR=1.71, 95% CI=1.29-2.27) and rhythm robustness (HR=1.97, 95% CI=1.50-2.60) than for those in the highest quartiles. Greater mortality from cancer (HR=2.09, 95% CI=1.04-4.22) and stroke (HR=2.64, 95% CI=1.11-6.30) was observed for later peak activity (after 4:33 p.m.; >1.5 SD from mean) than for the mean peak range (2:50-4:33 p.m.).
Older women with weak circadian activity rhythms have higher mortality risk. If confirmed in other cohorts, studies will be needed to test whether interventions (e.g., physical activity, bright light exposure) that regulate circadian activity rhythms will improve health outcomes in older adults.
Journal of the American Geriatrics Society 02/2010; 58(2):282-91. · 3.74 Impact Factor
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ABSTRACT: A possible familial component to fracture risk may be mediated through a genetic liability to fall recurrently.
Our analysis sample included 186 female sibling-ships (n=401) of mean age 71.9 yr (SD=5.0). Using variance component models, we estimated residual upper-limit heritabilities in fall-risk mobility phenotypes (e.g., chair-stand time, rapid step-ups, and usual-paced walking speed) and in recurrent falls. We also estimated familial and environmental (unmeasured) correlations between pairs of fall-risk mobility phenotypes. All models were adjusted for age, height, body mass index, and medical and environmental factors.
Residual upper-limit heritabilities were all moderate (P<0.05), ranging from 0.27 for usual-paced walking speed to 0.58 for recurrent falls. A strong familial correlation between usual-paced walking speed and rapid step-ups of 0.65 (P<0.01) was identified. Familial correlations between usual-paced walking speed and chair-stand time (-0.02) and between chair-stand time and rapid step-ups (-0.27) were both nonsignificant (P>0.05). Environmental correlations ranged from 0.35 to 0.58 (absolute values), P<0.05 for all.
There exists moderate familial resemblance in fall-risk mobility phenotypes and recurrent falls among older female siblings, which we expect is primarily genetic given that adult siblings live separate lives. All fall-risk mobility phenotypes may be coinfluenced at least to a small degree by shared latent familial or environmental factors; however, up to approximately one-half of the covariation between usual-paced walking speed and rapid step-ups may be due to a common set of genes.
Journal of Applied Physiology 02/2010; 108(5):1142-7. · 3.75 Impact Factor
