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.

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.

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.

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.