J Pfeilschifter

Obesity is not protective against fracture in postmenopausal women: GLOW

OBJECTIVE To investigate the prevalence and incidence of clinical fractures in obese, postmenopausal women enrolled in the Global Longitudinal study of Osteoporosis in Women (GLOW). METHODS This was a multinational, prospective, observational, population-based study carried out by 723 physician practices at 17 sites in 10 countries. A total of 60,393 women aged ≥ 55 years were included. Data were collected using self-administered questionnaires that covered domains that included patient characteristics, fracture history, risk factors for fracture, and anti-osteoporosis medications. RESULTS Body mass index (BMI) and fracture history were available at baseline and at 1 and 2 years in 44,534 women, 23.4% of whom were obese (BMI ≥ 30 kg/m(2)). Fracture prevalence in obese women at baseline was 222 per 1000 and incidence at 2 years was 61.7 per 1000, similar to rates in nonobese women (227 and 66.0 per 1000, respectively). Fractures in obese women accounted for 23% and 22% of all previous and incident fractures, respectively. The risk of incident ankle and upper leg fractures was significantly higher in obese than in nonobese women, while the risk of wrist fracture was significantly lower. Obese women with fracture were more likely to have experienced early menopause and to report 2 or more falls in the past year. Self-reported asthma, emphysema, and type 1 diabetes were all significantly more common in obese than nonobese women with incident fracture. At 2 years, 27% of obese women with incident fracture were receiving bone protective therapy, compared with 41% of nonobese and 57% of underweight women. CONCLUSIONS Our results demonstrate that obesity is not protective against fracture in postmenopausal women and is associated with increased risk of ankle and upper leg fractures.

Impact of Prevalent Fractures on Quality of Life: Baseline Results From the Global Longitudinal Study of Osteoporosis in Women

OBJECTIVE To examine several dimensions of health-related quality of life (HRQL) in postmenopausal women who report previous fractures, and to provide perspective by comparing these findings with those in other chronic conditions (diabetes, arthritis, lung disease). PATIENTS AND METHODS Fractures are a major cause of morbidity among older women. Few studies have examined HRQL in women who have had prior fractures and the effect of prior fracture location on HRQL. In this observational study of 57,141 postmenopausal women aged 55 years and older (enrollment from December 2007 to March 2009) from 17 study sites in 10 countries, HRQL was measured using the European Quality of Life 5 Dimensions Index (EQ-5D) and the health status, physical function, and vitality questions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). RESULTS Reductions in EQ-5D health-utility scores and SF-36-measured health status, physical function, and vitality were seen in association with 9 of 10 fracture locations. Spine, hip, and upper leg fractures resulted in the greatest reductions in quality of life (EQ-5D scores, 0.62, 0.64, and 0.61, respectively, vs 0.79 without prior fracture). Women with fractures at any of these 3 locations, as well as women with a history of multiple fractures (EQ-5D scores, 0.74 for 1 prior fracture, 0.68 for 2, and 0.58 for >/=3), had reductions in HRQL that were similar to or worse than those in women with other chronic diseases (0.67 for diabetes, 0.69 for arthritis, and 0.71 for lung disease). CONCLUSION Previous fractures at a variety of bone locations, particularly spine, hip, and upper leg, or involving more than 1 location are associated with significant reductions in quality of life.

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/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 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.

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 Parkinsons 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: Parkinsons 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. Parkinsons 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.

Frailty and Fracture, Disability, and Falls: A Multiple Country Study From the Global Longitudinal Study of Osteoporosis in Women

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.

Previous fractures at multiple sites increase the risk for subsequent fractures: the Global Longitudinal Study of Osteoporosis in Women.

Previous fractures of the hip, spine, or wrist are well‐recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women aged ≥55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow‐up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures, respectively, since age 45 years. During the first 2 years of follow‐up, 3149 women suffered 3683 incident fractures. Compared with women with no previous fractures, women with 1, 2, or ≥3 prior fractures were 1.8‐, 3.0‐, and 4.8‐fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1‐fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio [HR] = 7.3) and hip (HR = 3.5). Prior rib fractures were associated with a 2.3‐fold risk of subsequent vertebral fracture, and previous upper leg fracture predicted a 2.2‐fold increased risk of hip fracture. Women with a history of ankle fracture were at 1.8‐fold risk of future fracture of a weight‐bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development.

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.

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.

Predicting fractures in an international cohort using risk factor algorithms without BMD

Clinical risk factors are associated with increased probability of fracture in postmenopausal women. We sought to compare prediction models using self‐reported clinical risk factors, excluding BMD, to predict incident fracture among postmenopausal women. The GLOW study enrolled women aged 55 years or older from 723 primary‐care practices in 10 countries. The population comprised 19,586 women aged 60 years or older who were not receiving antiosteoporosis medication and were followed annually for 2 years. Self‐administered questionnaires were used to collect data on characteristics, fracture risk factors, previous fractures, and health status. The main outcome measure compares the C index for models using the WHO Fracture Risk (FRAX), the Garvan Fracture Risk Calculator (FRC), and a simple model using age and prior fracture. Over 2 years, 880 women reported incident fractures including 69 hip fractures, 468 “major fractures” (as defined by FRAX), and 583 “osteoporotic fractures” (as defined by FRC). Using baseline clinical risk factors, both FRAX and FRC showed a moderate ability to correctly order hip fracture times (C index for hip fracture 0.78 and 0.76, respectively). C indices for “major” and “osteoporotic” fractures showed lower values, at 0.61 and 0.64. Neither algorithm was better than the model based on age + fracture history alone (C index for hip fracture 0.78). In conclusion, estimation of fracture risk in an international primary‐care population of postmenopausal women can be made using clinical risk factors alone without BMD. However, more sophisticated models incorporating multiple clinical risk factors including falls were not superior to more parsimonious models in predicting future fracture in this population.

Predictors of treatment with osteoporosis medications after recent fragility fractures in a multinational cohort of postmenopausal women.

To determine the proportion of untreated women who reported receiving treatment after incident fracture and to identify factors that predict treatment across an international spectrum of individuals.