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.

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.

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.