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ABSTRACT: A high prevalence of obesity has recently been reported in postmenopausal women with low trauma fracture, suggesting that higher bone mineral density (BMD) in obese individuals may not be protective against fracture.
The aim of this study was to compare BMD and other risk factors for nonvertebral fracture in 1377 obese postmenopausal women.
Characteristics of obese women with and without incident nonvertebral fracture were investigated among the prospective cohort in the Study of Osteoporotic Fractures.
The Study of Osteoporotic Fractures is a multicenter study of 9704 women (>99% Caucasian) aged 65 yr and over who were recruited between September 1986 and October 1988 from population-based listings at four U.S. clinical centers.
The main outcome measure was nonvertebral fracture.
BMD T-scores in the spine, femoral neck, and total hip were significantly lower in obese women who experienced fractures than in obese women without fracture: mean differences, -0.56 [95% confidence interval (CI) = -0.73 to -0.39], -0.46 (95% CI = -0.57 to -0.36), and -0.51 (95% CI = -0.62 to -0.39), respectively (P < 0.0001 for all). A previous history of fracture [odds ratio = 1.69 (95% CI = 1.33-2.14); P < 0.0001] and femoral neck BMD [1.62 (95% CI = 1.42-1.85) per sd decrease in BMD; P < 0.0001] were independently associated with incident nonvertebral fracture.
Obese postmenopausal women who sustain nonvertebral fractures have significantly lower BMD on average than obese women without fracture and are more likely to have a past history of fracture. Fractures in obese postmenopausal women thus exhibit some characteristics of fragility fractures.
The Journal of clinical endocrinology and metabolism 06/2011; 96(8):2414-21. · 6.50 Impact Factor
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Meghan G Donaldson,
Peggy M Cawthon,
John T Schousboe,
Kristine E Ensrud,
Li-Yung Lui,
Jane A Cauley, Teresa A Hillier,
Brent C Taylor,
Marc C Hochberg,
Douglas C Bauer,
Steven R Cummings
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ABSTRACT: Fracture prediction models help to identify individuals at high risk who may benefit from treatment. Area under the curve (AUC) is used to compare prediction models. However, the AUC has limitations and may miss important differences between models. Novel reclassification methods quantify how accurately models classify patients who benefit from treatment and the proportion of patients above/below treatment thresholds. We applied two reclassification methods, using the National Osteoporosis Foundation (NOF) treatment thresholds, to compare two risk models: femoral neck bone mineral density (BMD) and age (simple model) and FRAX (FRAX model). The Pepe method classifies based on case/noncase status and examines the proportion of each above and below thresholds. The Cook method examines fracture rates above and below thresholds. We applied these to the Study of Osteoporotic Fractures (SOF). There were 6036 (1037 fractures) and 6232 (389 fractures) participants with complete data for major osteoporotic and hip fracture, respectively. Both models for major osteoporotic fracture (0.68 versus 0.69) and hip fracture (0.75 versus 0.76) had similar AUCs. In contrast, using reclassification methods, each model classified a substantial number of women differently. Using the Pepe method, the FRAX model (versus the simple model) missed treating 70 (7%) cases of major osteoporotic fracture but avoided treating 285 (6%) noncases. For hip fracture, the FRAX model missed treating 31 (8%) cases but avoided treating 1026 (18%) noncases. The Cook method (both models, both fracture outcomes) had similar fracture rates above/below the treatment thresholds. Compared with the AUC, new methods provide more detailed information about how models classify patients.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2011; 26(8):1767-73. · 6.04 Impact Factor
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Meghan G Donaldson,
Peggy M Cawthon,
Lily Y Lui,
John T Schousboe,
Kristine E Ensrud,
Brent C Taylor,
Jane A Cauley, Teresa A Hillier,
Thuy T Dam,
Jeff R Curtis,
Dennis M Black,
Douglas C Bauer,
Eric S Orwoll,
Steven R Cummings
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ABSTRACT: The new US National Osteoporosis Foundation's (NOF's) Clinician's Guide to Prevention and Treatment of Osteoporosis includes criteria for recommending pharmacologic treatment based on history of hip or vertebral fracture, femoral neck or spine bone mineral density (BMD) T-scores of -2.5 or less, and presence of low bone mass at the femoral neck or spine plus a 10-year risk of hip fracture of 3% or greater or of major osteoporotic fracture of 20% or greater. The proportion of men who would be recommended for treatment by these guidelines is not known. We applied the NOF criteria for treatment to men participating in the Osteoporotic Fractures in Men Study (MrOS). To determine how the MrOS population differs from the general US population of Caucasian men aged 65 years and older, we compared men in MrOS with men who participated in the National Health and Nutrition Examination Survey (NHANES) III on criteria included in the NOF treatment guidelines that were common to both cohorts. Compared with NHANES III, men in MrOS had higher femoral neck BMD values. Application of NOF guidelines to MrOS data estimated that at least 34% of US white men aged 65 years and older and 49% of those aged 75 years and older would be recommended for drug treatment. Application of the new NOF guidelines would result in recommending a very large proportion of white men in the United States for pharmacologic treatment of osteoporosis, for many of whom the efficacy of treatment is unknown.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2010; 25(7):1506-11. · 6.04 Impact Factor
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S R Patel,
T Blackwell,
S Redline,
S Ancoli-Israel,
J A Cauley, T A Hillier,
C E Lewis,
E S Orwoll,
M L Stefanick,
B C Taylor,
K Yaffe,
K L Stone
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ABSTRACT: Background: Reduced sleep has been reported to predict obesity in children and young adults. However, studies based on self-report have been unable to identify an association in older populations. In this study, the cross-sectional associations between sleep duration measured objectively and measures of weight and body composition were assessed in two cohorts of older adults.
International Journal of Obesity 10/2008; 32(12):1825-1834. · 4.69 Impact Factor
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S R Patel,
T Blackwell,
S Redline,
S Ancoli-Israel,
J A Cauley, T A Hillier,
C E Lewis,
E S Orwoll,
M L Stefanick,
B C Taylor,
K Yaffe,
K L Stone
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ABSTRACT: Reduced sleep has been reported to predict obesity in children and young adults. However, studies based on self-report have been unable to identify an association in older populations. In this study, the cross-sectional associations between sleep duration measured objectively and measures of weight and body composition were assessed in two cohorts of older adults.
Wrist actigraphy was performed for a mean (s.d.) of 5.2 (0.9) nights in 3055 men (age: 67-96 years) participating in the Osteoporotic Fractures in Men Study (MrOS) and 4.1 (0.8) nights in 3052 women (age: 70-99 years) participating in the Study of Osteoporotic Fractures (SOF). A subgroup of 2862 men and 455 women also underwent polysomnography to measure sleep apnea severity.
Compared to those sleeping an average of 7-8 h per night, and after adjusting for multiple risk factors and medical conditions, a sleep duration of less than 5 h was associated with a body mass index (BMI) that was on average 2.5 kg/m(2) (95% confidence interval (CI): 2.0-2.9) greater in men and 1.8 kg/m(2) (95% CI: 1.1-2.4) greater in women. The odds of obesity (BMI >or= 30 kg/m(2)) was 3.7-fold greater (95% CI: 2.7-5.0) in men and 2.3-fold greater in women (95% CI: 1.6-3.1) who slept less than 5 h. Short sleep was also associated with central body fat distribution and increased percent body fat. These associations persisted after adjusting for sleep apnea, insomnia and daytime sleepiness.
In older men and women, actigraphy-ascertained reduced sleep durations are strongly associated with greater adiposity.
International journal of obesity (2005) 10/2008; 32(12):1825-34. · 4.34 Impact Factor
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S P Moffett,
J I Oakley,
J A Cauley,
L Y Lui,
K E Ensrud,
B C Taylor, T A Hillier,
M C Hochberg,
J Li,
S Cayabyab,
J M Lee,
G Peltz,
S R Cummings,
J M Zmuda
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ABSTRACT: Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator nuclear factor kappa-beta that blocks osteoclastic bone resorption.
We investigated the association between a Lys3Asn polymorphism in the OPG gene and bone mineral density (BMD), and the risk of fracture in 6695 women aged 65 yr and older participating in the Study of Osteoporotic Fractures.
BMD was measured using either single-photon absorptiometry (Osteon Osteoanalyzer; Dove Medical Group, Los Angeles, CA) or dual-energy x-ray absorptiometry (Hologic QDR 1000; Hologic, Inc., Bedford, MA). Incident fractures were confirmed by physician adjudication of radiology reports. Genotyping was performed using an immobilized probe-based assay.
Women who were homozygous for the minor G (Lys) allele had significantly lower BMD at the intertrochanter, distal radius, lumbar spine, and calcaneus than those with the C (Asn) allele. There were 701 incident hip fractures during 13.6-yr follow-up (91,249 person-years), including 362 femoral neck and 333 intertrochanteric hip fractures. Women with the C/C (Asn-Asn) genotype had a 51% higher risk of femoral neck fracture (95% confidence interval, 1.13-2.02) and 26% higher risk of hip fracture (95% confidence interval, 1.02-1.54) than those with the G/G (Lys-Lys) genotype. These associations were independent of BMD. Intertrochanteric fractures were not associated with the Lys3Asn polymorphism.
These results require confirmation but suggest a role for the OPG Lys3Asn polymorphism in the genetic susceptibility to hip fractures among older white women.
Journal of Clinical Endocrinology & Metabolism 06/2008; 93(5):2002-8. · 6.50 Impact Factor
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S P Moffett,
J M Zmuda,
J I Oakley,
T J Beck,
J A Cauley,
K L Stone,
Li-Yung Lui,
K E Ensrud, T A Hillier,
M C Hochberg,
P Morin,
G Peltz,
D Greene,
S R Cummings
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ABSTRACT: TNFalpha is a proinflammatory cytokine that promotes osteoclastic bone resorption. We evaluated the association between a G-308A polymorphism (rs1800629) at the TNFA locus and osteoporosis phenotypes in 4306 older women participating in the Study of Osteoporotic Fractures. Femoral neck bone mineral density (BMD) and structural geometry were measured using dual-energy x-ray absorptiometry and hip structural analysis. Incident fractures were confirmed by physician adjudication of radiology reports. Despite similar femoral neck BMD, women with the A/A genotype had greater subperiosteal width (P = 0.01) and endocortical diameter (P = 0.03) than those with the G/G genotype. The net result of these structural differences was that there was a greater distribution of bone mass away from the neutral axis of the femoral neck in women with the A/A genotype, resulting in greater indices of bone bending strength (cross-sectional moment of inertia: P = 0.004; section modulus: P = 0.003). Among 376 incident hip fractures during 12.1 yr of follow-up, a 22% decrease in the risk of hip fracture was seen per copy of the A allele (relative risk 0.78; 95% confidence interval 0.63, 0.96), which was not influenced by adjustments for potential confounding factors, BMD, or bone strength indices. The G-308A polymorphism was not associated with a reduced risk of other fractures. These results suggest a potential role of genetic variation in TNFalpha in the etiology of osteoporosis.
Journal of Clinical Endocrinology & Metabolism 07/2005; 90(6):3491-7. · 6.50 Impact Factor
