• Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women

  Compston, Juliet E.; Wyman, Allison; FitzGerald, Gordon; Adachi, Jonathan D.; Chapurlat, Roland D.; Diez-Perez, Adolfo; Gehlbach, Stephen H.; Greenspan, Susan L.; Hooven, Frederick H.; LaCroix, Andrea Z.; et al. (2016-07-01)

  Increased fracture risk has been associated with weight loss in postmenopausal women, but the time course over which this occurs has not been established. The aim of this study was to examine the effects of unintentional weight loss of ≥10 lb (4.5 kg) in postmenopausal women on fracture risk at multiple sites up to 5 years after weight loss. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed the relationships between self-reported unintentional weight loss of ≥10 lb at baseline, year 2, or year 3 and incident clinical fracture in the years after weight loss. Complete data were available in 40,179 women (mean age ± SD 68 ± 8.3 years). Five-year cumulative fracture rate was estimated using the Kaplan-Meier method, and adjusted hazard ratios for weight loss as a time-varying covariate were calculated from Cox multiple regression models. Unintentional weight loss at baseline was associated with a significantly increased risk of fracture of the clavicle, wrist, spine, rib, hip, and pelvis for up to 5 years after weight loss. Adjusted hazard ratios showed a significant association between unintentional weight loss and fracture of the hip, spine, and clavicle within 1 year of weight loss, and these associations were still present at 5 years. These findings demonstrate increased fracture risk at several sites after unintentional weight loss in postmenopausal women. This increase is found as early as 1 year after weight loss, emphasizing the need for prompt fracture risk assessment and appropriate management to reduce fracture risk in this population. © 2016 American Society for Bone and Mineral Research.
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  Comparison between Frailty Index of Deficit Accumulation and Phenotypic Model to Predict Risk of Falls: Data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort

  Li, Guowei; Thabane, Lehana; Ioannidis, George; Kennedy, Courtney; Papaioannou, Alexandra (2015-03-12)

  OBJECTIVES: To compare the predictive accuracy of the frailty index (FI) of deficit accumulation and the phenotypic frailty (PF) model in predicting risks of future falls, fractures and death in women aged > /=55 years. METHODS: Based on the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF in risks of falls, fractures and death using three strategies: (1) investigated the relationship with adverse health outcomes by increasing per one-fifth (i.e., 20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the density distribution of the FI by the three groups (robust, pre-frail and frail) which were defined by the PF; (3) categorized the women according to a predicted probability function of falls during the third year of follow-up predicted by the FI. Logistic regression models were used for falls and death, while survival analyses were conducted for fractures. RESULTS: The FI and PF agreed with each other at a good level of consensus (correlation coefficients > /= 0.56) in all the three strategies. Both the FI and PF approaches predicted adverse health outcomes significantly. The FI quantified the risks of future falls, fractures and death more precisely than the PF. Both the FI and PF discriminated risks of adverse outcomes in multivariable models with acceptable and comparable area under the curve (AUCs) for falls (AUCs > /= 0.68) and death (AUCs > /= 0.79), and c-indices for fractures (c-indices > /= 0.69) respectively. CONCLUSIONS: The FI is comparable with the PF in predicting risks of adverse health outcomes. These findings may indicate the flexibility in the choice of frailty model for the elderly in the population-based settings.
• International management of bone health in glucocorticoid-exposed individuals in the observational GLOW study

  Silverman, S.; Flahive, Julie; Anderson, Frederick A. Jr.; Hooven, Fred H. (2015-01-01)
• Insights from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

  Watts, Nelson B.; GLOW Investigators (2014-07-01)

  GLOW is an observational, longitudinal, practice-based cohort study of osteoporosis in 60,393 women aged ≥ 55 years in 10 countries on three continents. In this Review, we present insights from the first 3 years of the study. Despite cost analyses being frequently based on spine and hip fractures, we found that nonvertebral, nonhip fractures were around five times more common and doubled the use of health-care resources compared with hip and spine fractures combined. Fractures not at the four so-called major sites in FRAX(®) (upper arm, forearm, hip and clinical vertebral fractures) account for > 40% of all fractures. The risk of fracture is increased by various comorbidities, such as Parkinson disease, multiple sclerosis and lung and heart disease. Obesity, although thought to be protective against all fractures, substantially increased the risk of fractures in the ankle or lower leg. Simple assessment by age plus fracture history has good predictive value for all fractures, but risk profiles differ for first and subsequent fractures. Fractures diminish quality of life as much or more than diabetes mellitus, arthritis and lung disease, yet women substantially underestimate their own fracture risk. Treatment rates in patients at high risk of fracture are below those recommended but might be too frequent in women at low risk. Comorbidities and the limits of current therapeutic regimens jeopardize the efficacy of drugs; new regimens should be explored for severe cases.
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  Frailty index of deficit accumulation and falls: data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort

  Li, Guowei; Ioannidis, George; Pickard, Laura; Kennedy, Courtney; Papaioannou, Alexandra; Thabane, Lehana; Adachi, Jonathan D. (2014-05-29)

  BACKGROUND: To investigate the association between frailty index (FI) of deficit accumulation and risk of falls, fractures, death and overnight hospitalizations in women aged 55 years and older. METHODS: The data were from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort. In this 3-year longitudinal, observational cohort study, women (N=3,985) aged ≥ 55 years were enrolled between May 2008 and March 2009 in Hamilton, Canada. A FI including co-morbidities, activities of daily living, symptoms and signs, and healthcare utilization was constructed using 34 health deficits at baseline. Relationship between the FI and falls, fractures, death and overnight hospitalizations was examined. RESULTS: The FI was significantly associated with age, with a mean rate of deficit accumulation across baseline age of 0.004 or 0.021 (on a log scale) per year. During the third year of follow-up, 1,068 (31.89%) women reported at least one fall. Each increment of 0.01 on the FI was associated with a significantly increased risk of falls during the third year of follow-up (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02-1.03). The area under the curve (AUC) of the predictive model was 0.69 (95% CI: 0.67-0.71). Results of subgroup and sensitivity analyses indicated the relationship between the FI and risk of falls was robust, while bootstrap analysis judged its internal validation. The FI was significantly related to fractures (hazard ratio [HR]: 1.02, 95% CI: 1.01-1.03), death (OR: 1.05, 95% CI: 1.03-1.06) during the 3-year follow-up period and overnight hospitalizations (incidence rate ratio [IRR]: 1.02, 95% CI: 1.02-1.03) for an increase of 0.01 on the FI during the third year of follow-up. Measured by per standard deviation (SD) increment of the FI, the ORs were 1.21 and 1.40 for falls and death respectively, while the HR was 1.17 for fractures and the IRR was 1.18 for overnight hospitalizations respectively. CONCLUSION: The FI of deficit accumulation increased with chronological age significantly. The FI was associated with and predicted increased risk of falls, fractures, death and overnight hospitalizations significantly.
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  Empirically based composite fracture prediction model from the Global Longitudinal Study of Osteoporosis in Postmenopausal Women (GLOW)

  FitzGerald, Gordon; Hosmer, David W. Jr.; Anderson, Frederick A. Jr.; Hooven, Fred H.; Gehlbach, Stephen H. (2014-03-01)

  CONTEXT: Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired. OBJECTIVE: The objective of the study was to improve model discrimination by developing a 5-year composite fracture prediction model for fracture sites that display similar risk profiles. DESIGN: This was a prospective, observational cohort study. SETTING: The study was conducted at primary care practices in 10 countries. PATIENTS: Women aged 55 years or older participated in the study. INTERVENTION: Self-administered questionnaires collected data on patient characteristics, fracture risk factors, and previous fractures. MAIN OUTCOME MEASURE: The main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age. RESULTS: Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index of 0.75, 47 066 women), and lowest for Fracture Risk Assessment Tool (FRAX) major fracture and a 10-site model (c indices of 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 years of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 years of age from a 10% decrease to a 60% increase. CONCLUSIONS: After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.
• Obesity, health-care utilization, and health-related quality of life after fracture in postmenopausal women: Global Longitudinal Study of Osteoporosis in Women (GLOW)

  Compston, Juliet E.; Flahive, Julie; Hooven, Fred H.; Anderson, Frederick A. Jr.; Gehlbach, Stephen H.; Boonen, Steven (2014-02-01)

  Fractures may be associated with higher morbidity in obese postmenopausal women than in nonobese women. We compared health-care utilization, functional status, and health-related quality of life (HRQL) in obese, nonobese, and underweight women with fractures. Information from the GLOW study, started in 2006, was collected at baseline and at 1, 2, and 3 years. In this subanalysis, self-reported incident clinical fractures, health-care utilization, HRQL, and functional status were recorded and examined. Women in GLOW (n = 60,393) were aged ≥55 years, from 723 physician practices at 17 sites in 10 countries. Complete data for fracture and body mass index were available for 90 underweight, 3,270 nonobese, and 941 obese women with one or more incident clinical fractures during the 3-year follow-up. The median hospital length of stay, adjusted for age, comorbidities, and fracture type, was significantly greater in obese than nonobese women (6 vs. 5 days, p = 0.017). Physical function and vitality score were significantly worse in obese than in nonobese women, both before and after fracture; but changes after fracture were similar across groups. Use of antiosteoporosis medication was significantly lower in obese than in nonobese or underweight women. In conclusion, obese women with fracture undergo a longer period of hospitalization for treatment and have poorer functional status and HRQL than nonobese women. Whether these differences translate into higher economic costs and adverse effects on longer-term outcomes remains to be established.
• Risk Factors for Treatment Failure With Antiosteoporosis Medication: The Global Longitudinal Study of Osteoporosis in Women (GLOW)

  Diez-Perez, Adolfo; Adachi, Jonathan D.; Adami, Silvano; Anderson, Frederick A. Jr.; Boonen, Steven; Compston, Juliet E.; Cooper, Cyrus; Gehlbach, Stephen H.; Greenspan, Susan L.; Hooven, Fred H.; et al. (2014-01-01)

  Antiosteoporosis medication (AOM) does not abolish fracture risk, and some individuals experience multiple fractures while on treatment. Therefore, criteria for treatment failure have recently been defined. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed risk factors for treatment failure, defined as sustaining two or more fractures while on AOM. GLOW is a prospective, observational cohort study of women aged ≥55 years sampled from primary care practices in 10 countries. Self-administered questionnaires collected data on patient characteristics, fracture risk factors, previous fractures, AOM use, and health status. Data were analyzed from women who used the same class of AOM continuously over 3 survey years and had data available on fracture occurrence. Multivariable logistic regression was used to identify independent predictors of treatment failure. Data from 26,918 women were available, of whom 5550 were on AOM. During follow-up, 73 of 5550 women in the AOM group (1.3%) and 123 of 21,368 in the non-AOM group (0.6%) reported occurrence of two or more fractures. The following variables were associated with treatment failure: lower Short Form 36 Health Survey (SF-36) score (physical function and vitality) at baseline, higher Fracture Risk Assessment Tool (FRAX) score, falls in the past 12 months, selected comorbid conditions, prior fracture, current use of glucocorticoids, need of arms to assist to standing, and unexplained weight loss ≥10 lb (≥4.5 kg). Three variables remained predictive of treatment failure after multivariable analysis: worse SF-36 vitality score (odds ratio [OR] per 10-point increase, 0.85; 95% confidence interval [CI], 0.76-0.95; p = 0.004); two or more falls in the past year (OR, 2.40; 95% CI, 1.34-4.29; p = 0.011), and prior fracture (OR, 2.93; 95% CI, 1.81-4.75; p < 0.0001). The C statistic for the model was 0.712. Specific strategies for fracture prevention should therefore be developed for this subgroup of patients. © 2014 American Society for Bone and Mineral Research.
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  When, Where and How Osteoporosis-Associated Fractures Occur: An Analysis from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

  Costa, Aline G.; Wyman, Allison; Siris, Ethel S.; Watts, Nelson B.; Silverman, Stuart; Roux, Christian; Rossini, Maurizio; Pfeilschifter, Johannes; Nieves, Jeri W.; Netelenbos, J. Coen; et al. (2013-12-11)

  Objective: To examine when, where and how fractures occur in postmenopausal women. Methods: We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3. Results: Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68–86% of NHNV and 68–83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling. Conclusion: In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.
• Concern and risk perception of osteoporosis and fracture among post-menopausal Australian women: results from the Global Longitudinal Study of Osteoporosis in Women (GLOW) cohort

  Barcenilla-Wong, A L.; Chen, J S.; March, L M. (2013-10-01)

  PURPOSE: The purpose of this study is to identify factors associated with concern and perception of risks of osteoporosis and osteoporotic fractures and determine whether bone mineral density (BMD) testing influenced concern and risk perception. METHODS: Study subjects (n = 1,082, age 55-94 years) were female Australian participants of the Global Longitudinal Study of Osteoporosis in Women (GLOW). Self-administered questionnaires were sent annually from 2007 to 2010. Study outcomes included 'concern about osteoporosis', 'perception of getting osteoporosis' and 'perception of fracture risk' compared to similar aged women. The closest post-BMD testing or baseline questionnaires were used for women with and without BMD testing, respectively. Multinomial logistic regression was used for the analysis. RESULTS: BMD testing, prior fracture after age 45, younger age and lower self-reported general health were significantly associated with being 'very' or 'somewhat concerned' about osteoporosis and having a 'much higher' or 'little higher' risk perception of osteoporosis and fractures. A poorer BMD result was associated with higher concern and higher risk perceptions. The presence of comorbidities, having >/=2 falls in the preceding year and maternal osteoporosis were associated with higher concern. Maternal osteoporosis, presence of comorbidities, weight loss of >/=5 kg in the preceding year and low body mass index were associated with higher perceptions of osteoporosis risk. CONCLUSION: Women's concern and risk perception of osteoporosis and osteoporotic fractures were reasonably well founded. However, increasing age, height loss, smoking and drinking were not associated with concern and perception despite being known osteoporosis risk factors. These factors should be considered in planning for education and awareness raising programmes.
• Disease-specific perception of fracture risk and incident fracture rates: GLOW cohort study

  Gregson, C. L.; Dennison, Elaine M.; Compston, Juliet E.; Adami, Silvano; Adachi, Jonathan D.; Boonen, Steven; Chapurlat, Roland D.; Diez-Perez, Adolfo; Greenspan, Susan L.; Hooven, Frederick H.; et al. (2013-07-26)

  Accurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles. INTRODUCTION: We compared self-perceived fracture risk and 3-year incident fracture rates in postmenopausal women with a range of morbidities in the Global Longitudinal study of Osteoporosis in Women (GLOW). METHODS: GLOW is an international cohort study involving 723 physician practices across ten countries (Europe, North America, Australasia); 60,393 women aged >/=55 years completed baseline questionnaires detailing medical history and self-perceived fracture risk. Annual follow-up determined self-reported incident fractures. RESULTS: In total 2,945/43,832 (6.8 %) sustained an incident fracture over 3 years. All morbidities were associated with increased fracture rates, particularly Parkinson's disease (hazard ratio [HR]; 95 % confidence interval [CI], 3.89; 2.78-5.44), multiple sclerosis (2.70; 1.90-3.83), cerebrovascular events (2.02; 1.67-2.46), and rheumatoid arthritis (2.15; 1.53-3.04) (all p < 0.001). Most individuals perceived their fracture risk as similar to (46 %) or lower than (36 %) women of the same age. While increased self-perceived fracture risk was strongly associated with incident fracture rates, only 29 % experiencing a fracture perceived their risk as increased. Under-appreciation of fracture risk occurred for all morbidities, including neurological disease, where women with low self-perceived fracture risk had a fracture HR 2.39 (CI 1.74-3.29) compared with women without morbidities. CONCLUSIONS: Postmenopausal women with morbidities tend to under-appreciate their risk, including in the context of neurological diseases, where fracture rates were highest in this cohort. This has important implications for health education, particularly among women with Parkinson's disease, multiple sclerosis, or cerebrovascular disease.
• Relationship of weight, height, and body mass index with fracture risk at different sites in postmenopausal women: The global longitudinal study of osteoporosis in women (GLOW)

  Compston, Juliet E.; Flahive, Julie M.; Hosmer, David W. Jr.; Watts, Nelson B.; Siris, Ethel S.; Saag, Kenneth G.; Roux, Christian; Rossini, Maurizio; Pfeilschifter, Johannes; Nieves, Jeri W.; et al. (2013-07-22)

  Low body mass index (BMI) is a well-established risk factor for fracture in postmenopausal women. Height and obesity have also been associated with increased fracture risk at some sites. We investigated the relationships of weight, BMI, and height with incident clinical fracture in a practice-based cohort of postmenopausal women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). Data were collected at baseline and 1, 2, and 3 years. For hip, spine, wrist, pelvis, rib, upper arm/shoulder, clavicle, ankle, lower leg, and upper leg fractures, we modeled the time to incident self-reported fracture over a 3-year period using the Cox proportional hazards model and fitted the best linear or non-linear models containing height, weight, and BMI. Of 52,939 women, 3628 (6.9%) reported an incident clinical fracture during the 3-year follow-up period. Linear BMI showed a significant inverse association with hip, clinical spine, and wrist fractures: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) per increase of 5 kg/m2 were 0.80 (0.71-0.90), 0.83 (0.76-0.92), and 0.88 (0.83-0.94), respectively (all p < 0.001). For ankle fractures, linear weight showed a significant positive association: adjusted HR per 5-kg increase 1.05 (1.02-1.07) (p < 0.001). For upper arm/shoulder and clavicle fractures, only linear height was significantly associated: adjusted HRs per 10-cm increase were 0.85 (0.75-0.97) (p = 0.02) and 0.73 (0.57-0.92) (p = 0.009), respectively. For pelvic and rib fractures, the best models were for non-linear BMI or weight (p = 0.05 and 0.03, respectively), with inverse associations at low BMI/body weight and positive associations at high values. These data demonstrate that the relationships between fracture and weight, BMI, and height are site-specific. The different associations may be mediated, at least in part, by effects on bone mineral density, bone structure and geometry, and patterns of falling.
• Frailty and Fracture, Disability, and Falls: A Multiple Country Study From the Global Longitudinal Study of Osteoporosis in Women

  Tom, Sarah E.; Adachi, Jonathan D.; Anderson, Frederick A. Jr.; Boonen, Steven; Chapurlat, Roland D.; Cooper, Cyrus; Gehlbach, Stephen H.; Greenspan, Susan L.; Hooven, Frederick H.; Nieves, Jeri W.; et al. (2013-01-25)

  Objectives To test whether women aged 55 and older with increasing evidence of a frailty phenotype would have greater risk of fractures, disability, and recurrent falls than women who were not frail, across geographic areas (Australia, Europe, and North America) and age groups. Design Multinational, longitudinal, observational cohort study. Setting Global Longitudinal Study of Osteoporosis in Women (GLOW). Participants Women (N = 48,636) aged 55 and older enrolled at sites in Australia, Europe, and North America. Measurements Components of frailty (slowness and weakness, poor endurance and exhaustion, physical activity, and unintentional weight loss) at baseline and report of fracture, disability, and recurrent falls at 1 year of follow-up were investigated. Women also reported health and demographic characteristics at baseline. Results Women younger than 75 from the United States were more likely to be prefrail and frail than those from Australia, Canada, and Europe. The distribution of frailty was similar according to region for women aged 75 and older. Odds ratios from multivariable models for frailty versus nonfrailty were 1.23 (95% confidence interval (CI) = 1.07–1.42) for fracture, 2.29 (95% CI = 2.09–2.51) for disability, and 1.68 (95% CI = 1.54–1.83) for recurrent falls. The associations for prefrailty versus nonfrailty were weaker but still indicated statistically significantly greater risk of each outcome. Overall, associations between frailty and each outcome were similar across age and geographic region. Conclusion Greater evidence of a frailty phenotype is associated with greater risk of fracture, disability, and falls in women aged 55 and older in 10 countries, with similar patterns across age and geographic region.
• Characteristics associated with anti-osteoporosis medication use: data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) USA cohort

  Guggina, Pamela; Flahive, Julie; Hooven, Frederick H.; Watts, Nelson B.; Siris, Ethel S.; Roux, Christian; Pfeilschifter, Johannes; Greenspan, Susan L.; Diez-Perez, Adolfo; Cooper, Cyrus; et al. (2012-12-01)

  INTRODUCTION: Many women at risk of fracture do not receive anti-osteoporosis medication (AOM), while others may be receiving unnecessary treatment. PURPOSE: To examine the characteristics associated with AOM use among women at low and high risks of fracture. METHODS: The Global Longitudinal Study of Osteoporosis in Women (GLOW) is a prospective cohort study in which data were collected, via self-administered questionnaires, from 60,393 non-institutionalized women aged >/= 55 years in 10 countries between October 1, 2006 and April 30, 2008. This is a cross-sectional analysis of baseline USA data, in which women were classified as having low fracture risk (<65 >years; no FRAX risk factors) or high fracture risk (>/=65 years; prior fracture or >/= 2 other FRAX risk factors). RESULTS: Of 27,957 women, 3013 were at low risk of fracture and 3699 were at high risk. Only 35.7% of high-risk women reported AOM treatment, rising to 39.5% for those with self-reported osteopenia and 65.4% for those with self-reported osteoporosis. Conversely, 13.4% of low-risk women reported AOM, rising to 28.7% for osteopenia and 62.4% for osteoporosis. Characteristics associated with significantly higher AOM treatment rates among low- and high-risk women were: osteoporosis (odds ratios 75.3 and 18.1, respectively), osteopenia (17.9 and 6.3), concern about osteoporosis (2.0 and 1.8), higher perceived risk of fracture (2.3 and 1.6), and higher vitality score (1.7 and 1.6). CONCLUSION: Use of AOM is frequently inconsistent with published guidelines in both high- and low-risk women. Characteristics other than FRAX fracture risk appear to influence this use, particularly the presence of self-reported osteoporosis.
• Differing risk profiles for individual fracture sites: Evidence from the global longitudinal study of osteoporosis in women (GLOW)

  FitzGerald, Gordon; Boonen, Steven; Compston, Juliet E.; Pfeilschifter, Johannes; LaCroix, Andrea Z.; Hooven, Frederick H.; Gehlbach, Stephen H. (2012-09-01)

  The purposes of this study were to examine fracture risk profiles at specific bone sites, and to understand why model discrimination using clinical risk factors is generally better in hip fracture models than in models that combine hip with other bones. Using 3-year data from the GLOW study (54,229 women with more than 4400 total fractures), we present Cox regression model results for 10 individual fracture sites, for both any and first-time fracture, among women aged >/=55 years. Advanced age is the strongest risk factor in hip (hazard ratio [HR] = 2.3 per 10-year increase), pelvis (HR = 1.8), upper leg (HR = 1.8), and clavicle (HR = 1.7) models. Age has a weaker association with wrist (HR = 1.1), rib (HR = 1.2), lower leg (not statistically significant), and ankle (HR = 0.81) fractures. Greater weight is associated with reduced risk for hip, pelvis, spine, and wrist, but higher risk for first lower leg and ankle fractures. Prior fracture of the same bone, although significant in nine of 10 models, is most strongly associated with spine (HR = 6.6) and rib (HR = 4.8) fractures. Past falls are important in all but spine models. Model c indices are >/=0.71 for hip, pelvis, upper leg, spine, clavicle, and rib, but
• Regional and age-related variations in the proportions of hip fractures and major fractures among postmenopausal women: the Global Longitudinal Study of Osteoporosis in Women

  Pfeilschifter, Johannes; Cooper, C.; Watts, Nelson B.; Flahive, Julie; Saag, Kenneth G.; Boonen, Steven; Chapurlat, Roland D.; Compston, Juliet E.; Diez-Perez, Adolfo; LaCroix, Andrea Z.; et al. (2012-08-01)

  We examined variations in proportions of hip fractures and major fractures among postmenopausal women using the Global Longitudinal Study of Osteoporosis in Women (GLOW). The proportion of major fractures that were hip fractures varied with age and region, whereas variations in the proportion of fractures that were major fractures appeared modest. INTRODUCTION: In many countries, the World Health Organization fracture risk assessment tool calculates the probability of major fractures by assuming a uniform age-associated proportion of major fractures that are hip fractures in different countries. We further explored this assumption, using data from the GLOW. METHODS: GLOW is an observational population-based study of 60,393 non-institutionalized women aged >/=55 years who had visited practices within the previous 2 years. Main outcome measures were self-reported prevalent fractures after the age of 45 years and incident fractures during the 2 years of follow-up. RESULTS: The adjusted proportion of prevalent and incident major fractures after the age of 45 years that were hip fractures was higher in North America (16%, 17%) than in northern (13%, 12%) and southern Europe (10%, 10%), respectively. The proportion of incident major fractures that were hip fractures increased more than five-fold with age, from 6.6% among 55-59-year-olds to 34% among those aged >/=85 years. Regional and age-associated variations in the proportion of all incident fractures that were major fractures were less marked, not exceeding 16% and 28%, respectively. CONCLUSIONS: The data suggest that there may be regional differences in the proportion of major fractures that are hip fractures in postmenopausal women. In contrast, the regional and age-related variations in the proportion of fractures that are major fractures appear to be modest. However, because of the limited number of fractures in our sample, further studies are necessary to confirm these findings.
• An increased rate of falling leads to a rise in fracture risk in postmenopausal women with self-reported osteoarthritis: a prospective multinational cohort study (GLOW)

  Prieto-Alhambra, Daniel; Nogues, Xavier; Javaid, M. Kassim; Wyman, Allison; Arden, Nigel K.; Cooper, Cyrus; Adachi, Jonathan D.; Boonen, Steven; Chapurlat, Roland D.; Compston, Juliet E.; et al. (2012-06-23)

  OBJECTIVES: Patients with osteoarthritis have increased bone mass METHODS: The Global Longitudinal Study of Osteoporosis in Women is a prospective multinational cohort of 60 393 non-institutionalised women aged ≥55 years who had visited primary care practices within the previous 2 years. Questionnaires were mailed at yearly intervals. Patients were classified as having osteoarthritis if they answered yes to the question, 'Has a doctor or other health provider ever said that you had osteoarthritis or degenerative joint disease?', and this was validated against primary care records in a subsample. Information on incident falls, fractures and covariates was self-reported. Cox and Poisson models were used for incident fractures and number of falls, respectively, to compute hazard ratios (HRs) and rate ratios (RRs) for baseline osteoarthritis status. RESULTS: Of 51 386 women followed for a median of 2.9 years (interquartile range 2.1-3.0), 20 409 (40%) reported osteoarthritis. The adjusted HR for osteoarthritis predicting fracture was 1.21 (95% CI 1.13 to 1.30; p CONCLUSIONS: Postmenopausal women with self-reported osteoarthritis have a 20% increased risk of fracture and experience 25% more falls than those without osteoarthritis. These data suggest that increased falls are the causal pathway of the association between osteoarthritis and fractures.
• Effect of co-morbidities on fracture risk: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

  Dennison, Elaine M.; Compston, Juliet E.; Flahive, Julie; Siris, Ethel S.; Gehlbach, Stephen H.; Boonen, Steven; Chapurlat, Roland D.; Diez-Perez, Adolfo; Anderson, Frederick A. Jr.; Hooven, Frederick H.; et al. (2012-06-01)

  INTRODUCTION: Greater awareness of the relationship between co-morbidities and fracture risk may improve fracture-prediction algorithms such as FRAX. MATERIALS AND METHODS: We used a large, multinational cohort study (GLOW) to investigate the effect of co-morbidities on fracture risk. Women completed a baseline questionnaire detailing past medical history, including co-morbidity history and fracture. They were re-contacted annually to determine incident clinical fractures. A co-morbidity index, defined as number of baseline co-morbidities, was derived. The effect of adding the co-morbidity index to FRAX risk factors on fracture prevention was examined using chi-squared tests, the May-Hosmer test, c index and comparison of predicted versus observed fracture rates. RESULTS: Of 52,960 women with follow-up data, enrolled between October 2006 and February 2008, 3224 (6.1%) sustained an incident fracture over 2 years. All recorded co-morbidities were significantly associated with fracture, except for high cholesterol, hypertension, celiac disease, and cancer. The strongest association was seen with Parkinson's disease (age-adjusted hazard ratio [HR]: 2.2; 95% CI: 1.6-3.1; P<0.001). Co-morbidities that contributed most to fracture prediction in a Cox regression model with FRAX risk factors as additional predictors were: Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, osteoarthritis, and heart disease. CONCLUSION: Co-morbidities, as captured in a co-morbidity index, contributed significantly to fracture risk in this study population. Parkinson's disease carried a particularly high risk of fracture; and increasing co-morbidity index was associated with increasing fracture risk. Addition of co-morbidity index to FRAX risk factors improved fracture prediction.
• Non-hip, non-spine fractures drive healthcare utilization following a fracture: the Global Longitudinal Study of Osteoporosis in Women (GLOW)

  Ioannidis, G.; Flahive, Julie; Pickard, L.; Papaioannou, A.; Chapurlat, Roland D.; Silverman, Stuart; Anderson, Frederick A. Jr.; Gehlbach, Stephen H.; Hooven, Frederick H.; Boonen, Steven; et al. (2012-04-12)

  We evaluated healthcare utilization associated with treating fracture types in >51,000 women aged >/=55 years. Over the course of 1 year, there were five times more non-hip, non-spine fractures than hip or spine fractures, resulting in twice as many days of hospitalization and rehabilitation/nursing home care for non-hip, non-spine fractures. INTRODUCTION: The purpose of this study is to evaluate medical healthcare utilization associated with treating several types of fractures in women >/=55 years from various geographic regions. METHODS: Information from the Global Longitudinal Study of Osteoporosis in Women (GLOW) was collected via self-administered patient questionnaires at baseline and year 1 (n = 51,491). Self-reported clinically recognized low-trauma fractures at year 1 were classified as incident spine, hip, wrist/hand, arm/shoulder, pelvis, rib, leg, and other fractures. Healthcare utilization data were self-reported and included whether the fracture was treated at a doctor's office/clinic or at a hospital. Patients were asked if they had undergone surgery or been treated at a rehabilitation center or nursing home. RESULTS: During 1-year follow-up, there were 195 spine, 134 hip, and 1,654 non-hip, non-spine fractures. Clinical vertebral fractures resulted in 617 days of hospitalization and 512 days of rehabilitation/nursing home care; hip fractures accounted for 1,306 days of hospitalization and 1,650 days of rehabilitation/nursing home care. Non-hip, non-spine fractures resulted in 3,805 days in hospital and 5,186 days of rehabilitation/nursing home care. CONCLUSIONS: While hip and vertebral fractures are well recognized for their associated increase in health resource utilization, non-hip, non-spine fractures, by virtue of their 5-fold greater number, require significantly more healthcare resources.
• Burden of non-hip, non-vertebral fractures on quality of life in postmenopausal women : The Global Longitudinal study of Osteoporosis in Women (GLOW)

  Roux, Christian; Wyman, Allison; Hooven, Frederick H.; Gehlbach, Stephen H.; Adachi, Jonathan D.; Compston, Juliet E.; Cooper, C.; Diez-Perez, Adolfo; Greenspan, Susan L.; LaCroix, Andrea Z.; et al. (2012-03-08)

  Among 50,461 postmenopausal women, 1,822 fractures occurred (57% minor non-hip, non-vertebral [NHNV], 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D, followed by major NHNV and hip fractures. Decreases in physical function and health status were greatest for spine or hip fractures. INTRODUCTION: There is growing evidence that NHNV fractures result in substantial morbidity and healthcare costs. The aim of this prospective study was to assess the effect of these NHNV fractures on quality of life. METHODS: We analyzed the 1-year incidences of hip, spine, major NHNV (pelvis/leg, shoulder/arm) and minor NHNV (wrist/hand, ankle/foot, rib/clavicle) fractures among women from the Global Longitudinal study of Osteoporosis in Women (GLOW). Health-related quality of life (HRQL) was analyzed using the EuroQol EQ-5D tool and the SF-36 health survey. RESULTS: Among 50,461 women analyzed, there were 1,822 fractures (57% minor NHNV, 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D summary scores, followed by major NHNV and hip fractures. The number of women with mobility problems increased most for those with major NHNV and spine fractures (both +8%); spine fractures were associated with the largest increases in problems with self care (+11%), activities (+14%), and pain/discomfort (+12%). Decreases in physical function and health status were greatest for those with spine or hip fractures. Multivariable modeling found that EQ-5D reduction was greatest for spine fractures, followed by hip and major/minor NHNV. Statistically significant reductions in SF-36 physical function were found for spine fractures, and were borderline significant for major NHNV fractures. CONCLUSION: This prospective study shows that NHNV fractures have a detrimental effect on HRQL. Efforts to optimize the care of osteoporosis patients should include the prevention of NHNV fractures.

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