Obesity, health-care utilization, and health-related quality of life after fracture in postmenopausal women: Global Longitudinal Study of Osteoporosis in Women (GLOW).

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.

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).

OBJECTIVES: Patients with osteoarthritis have increased bone mass but no decrease in fractures. The association between self-reported osteoarthritis and incident falls and fractures was studied in postmenopausal women. 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<0.0001) and the adjusted RR for falls was 1.24 (95% CI 1.22 to 1.26; p<0.0001). However, the association between osteoarthritis and fracture was not significant after adjustment for incident falls (HR 1.06 (95% CI 0.98 to 1.15; p=0.13)). 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.

The association of lean mass and fat mass with peak bone mass in young premenopausal women.

Total body mass is a major determinant of bone mass, but studies of the relative contributions of lean mass (LM) and fat mass (FM) to bone mass have yielded conflicting results. This is likely because of the use of bone measures that are not adequately adjusted for body size and, therefore, not appropriate for analyses related to body composition, which is also correlated with body size. We examined the relationship between body composition and peak bone mass in premenopausal women aged 18-30 yr using both size-dependent and size-adjusted measures of bone density and body composition, as well as statistical models adjusted for size-related factors. We measured total bone mass and areal bone density using dual-energy X-ray absorptiometry, and used established formulas to calculate estimates of volumetric (size-adjusted) bone density. LM tended to be positively associated with bone both before and after adjustment for size-related factors. FM and body fat percentage, however, were positively associated with size-dependent bone measures, but adjusting for size removed or reversed this association. These findings suggest that the association between bone mass and body composition, especially FM, is dependent on the bone measures analyzed, and that determining the most appropriate size-adjustment techniques is critical for understanding this relationship.

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

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.

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).

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 at 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 nonlinear 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/m(2) 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 nonlinear 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.

Risk factors for treatment failure with antiosteoporosis medication: the global longitudinal study of osteoporosis in women (GLOW).

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.

Empirically based composite fracture prediction model from the Global Longitudinal Study of Osteoporosis in Postmenopausal Women (GLOW).

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.

Frailty and fracture, disability, and falls: a multiple country study from the global longitudinal study of osteoporosis in women.

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.

When, where and how osteoporosis-associated fractures occur: an analysis from the Global Longitudinal Study of Osteoporosis in Women (GLOW).

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.

Differing risk profiles for individual fracture sites: evidence from the Global Longitudinal Study of Osteoporosis in Women (GLOW).

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 ≤0.66 for upper arm/shoulder, lower leg, wrist, and ankle fractures. The c index for combining hip, spine, upper arm, and wrist (major fracture) is 0.67. First-time fracture models have c indices ranging from 0.59 for wrist to 0.78 for hip and pelvis. The c index for first-time major fracture is 0.63. In conclusion, substantial differences in risk profiles exist among the 10 bones considered.

Effect of co-morbidities on fracture risk: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW).

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.

Regional differences in treatment for osteoporosis. The Global Longitudinal Study of Osteoporosis in Women (GLOW).

PURPOSE: To determine if important geographic differences exist in treatment rates for osteoporosis and whether this variation can be explained by regional variation in risk factors. METHODS: The Global Longitudinal Study of Osteoporosis in Women is an observational study of women ≥55 years sampled from primary care practices in 10 countries. Self-administered questionnaires were used to collect data on patient characteristics, risk factors for fracture, previous fractures, anti-osteoporosis medication, and health status. RESULTS: Among 58,009 women, current anti-osteoporosis medication use was lowest in Northern Europe (16%) and highest in U.S.A. and Australia (32%). Between 48% (U.S.A., Southern Europe) and 68% (Northern Europe) of women aged ≥65 years with a history of spine or hip fracture since age 45 were untreated. Among women with osteoporosis, the percentage of treated cases was lowest in Europe (45-52% versus 62-65% elsewhere). Women with osteopenia and no other risk factors were treated with anti-osteoporosis medication most frequently in U.S.A. (31%) and Canada (31%), and least frequently in Southern Europe (12%), Northern Europe (13%), and Australia (16%). After adjusting for risk factors, U.S. women were threefold as likely to be treated with anti-osteoporosis medication as Northern European women (odds ratio 2.8; 95% confidence interval 2.5-3.1) and 1.5 times as likely to be treated as Southern European women (1.5, 1.4-1.6). Up to half of women reporting previous hip or spine fracture did not receive treatment. CONCLUSIONS: The likelihood of being treated for osteoporosis differed between regions, and cannot be explained by variation in risk factors. Many women at risk of fracture do not receive prophylaxis.

Trends in prevention of glucocorticoid-induced osteoporosis.

OBJECTIVE: To determine longitudinal patterns and predictors for the utilization of bone mass measurements and anti-osteoporotic medications in the prevention of glucocorticoid-induced osteoporosis. METHODS: Within a managed care population of 7 million persons, we identified 3,125 adult men and women who had initiated longterm glucocorticoid therapy (>or=7.5 mg/day of prednisone equivalent for > 6 mo). The study population was examined by 3 biennial intervals between years 1996 and 2001 for receipt of a bone mass measurement and use of anti-osteoporotic medication (bisphosphonate, calcitonin, raloxifene, hormone replacement therapy). RESULTS: Receipt of a bone mass measurement increased among postmenopausal women from 10% in 1996-97 to 19% in 2000-01, but remained below 6% in all biennial intervals among women under age 50 and men. The use of anti-osteoporotic medication was most common among postmenopausal women, where it approached 50%. The largest absolute increase in anti-osteoporotic medication utilization was among women ages 65 and over, increasing from 24% in 1996-97 to 44% in 2000-01. The specialty of physician providing care was associated with receipt of both testing and treatment. Odds of receipt of a bone mass measurement and anti-osteoporotic medication were 3 to 4 times greater among patients of rheumatologists compared to those of internists or family practitioners. CONCLUSION: Among patients initiating longterm glucocorticoid therapy, the proportion of individuals receiving a bone mass measurement or anti-osteoporotic medication remains relatively low, but has improved temporally among postmenopausal women.

Follow-up treatment for osteoporosis after fracture.

Studies of the management of osteoporosis in older women who have had hip or wrist fractures have found underdiagnosis and undertreatment of the disease. Few such studies have been conducted in the United States, however, and most studies have been confined to a subset of the treatments currently available to treat osteoporosis. Mail surveys were sent to 381 women between 50 and 84 years of age who had been treated for a hip or wrist fracture at a large northeast US teaching hospital between October 1, 1998, and September 30, 2000. These surveys included questions about osteoporosis risk factors and physician treatment both before and after the index fracture. Of 381 surveys mailed, 70 were returned because of an invalid address or by a relative because a patient was deceased. Of the remaining 311 surveys, 147 completed responses were received. Fifty-two percent of respondents reported having received either a prescription or a recommendation for a nonprescription medication used to treat osteoporosis before the fracture. After fracture, 60% of subjects were advised to take any osteoporosis medication, and 42% of were advised to take a prescription medication. Of women reporting no treatment advice before fracture, 33% reported treatment after. Twenty-four percent of patients reported a change in treatment after fracture versus before. No significant differences in treatment were found according to fracture history, maternal history of fracture, or maternal history of osteoporosis. Both prescription and nonprescription treatment prevalence after fracture were lower than expected, and there was only a small change in reported treatment prevalence after fracture versus before. There was also little difference in treatment prevalence based on risk factors for osteoporosis or osteoporotic fractures. A sizeable opportunity exists for intervention to reduce the risk of osteoporotic fractures for patients who have a history of fracture.

Recognition of osteoporosis by primary care physicians.

OBJECTIVES: This study explored the recognition and treatment of osteoporosis and vertebral fracture among older women by primary care physicians. METHODS: Data from the National Ambulatory Medical Care Survey from 1993 to 1997 were examined for evidence of diagnosis and treatment of osteoporosis or vertebral fracture during visits by White women 60 years and older to primary care physicians. RESULTS: Fewer than 2% of the women received diagnoses of osteoporosis or vertebral fracture, although expected prevalence is 20% to 30%. Appropriate drug treatment, including antiresorptive agents and calcium and vitamin D, was offered to only 36% of the diagnosed patients. CONCLUSIONS: Few cases of osteoporosis or vertebral fracture in older women are being diagnosed and treated by primary care physicians.