WHO absolute fracture risk models (FRAX): do clinical risk factors improve fracture prediction in older women without osteoporosis?

Abstract

Bone mineral density (BMD) is a strong predictor of fracture, yet most fractures occur in women without osteoporosis by BMD criteria. To improve fracture risk prediction, the World Health Organization recently developed a country-specific fracture risk index of clinical risk factors (FRAX) that estimates 10-year probabilities of hip and major osteoporotic fracture. Within differing baseline BMD categories, we evaluated 6252 women aged 65 or older in the Study of Osteoporotic Fractures using FRAX 10-year probabilities of hip and major osteoporotic fracture (ie, hip, clinical spine, wrist, and humerus) compared with incidence of fractures over 10 years of follow-up. Overall ability of FRAX to predict fracture risk based on initial BMD T-score categories (normal, low bone mass, and osteoporosis) was evaluated with receiver-operating-characteristic (ROC) analyses using area under the curve (AUC). Over 10 years of follow-up, 368 women incurred a hip fracture, and 1011 a major osteoporotic fracture. Women with low bone mass represented the majority (n = 3791, 61%); they developed many hip (n = 176, 48%) and major osteoporotic fractures (n = 569, 56%). Among women with normal and low bone mass, FRAX (including BMD) was an overall better predictor of hip fracture risk (AUC = 0.78 and 0.70, respectively) than major osteoporotic fractures (AUC = 0.64 and 0.62). Simpler models (eg, age + prior fracture) had similar AUCs to FRAX, including among women for whom primary prevention is sought (no prior fracture or osteoporosis by BMD). The FRAX and simpler models predict 10-year risk of incident hip and major osteoporotic fractures in older US women with normal or low bone mass.

Figure 1

FRAX predicted 10-year hip probabilities with FN BMD are compared to observed fracture across baseline BMD increments. Observed fractures are plotted as total number of fractures for each BMD T-score group, and BMD distribution of the population is indicated on each graph. FRAX hip probabilities were used to predict hip fracture; major osteoporotic probabilities were used to predict major osteoporotic fractures. Major osteoporotic fractures were defined as hip, clinical spine, wrist and humerus.⁽⁶⁾ *p<0.05 by paired t-tests of predicted vs. observed fractures in each respective 0.5 BMD T-score increment.

Figure 2

Proportion of women with low bone mass (n=4464) at baseline exam that would meet current National Osteoporosis (NOF) treatment thresholds (high-risk; n=2218) or not (low-risk; n=2246), with further stratification on whether fracture occurred in 10 years of follow-up. NOF high-risk is low bone mass (T score between −1.0 and −2.5 by femoral neck or spine BMD) and 10 year FRAX (including BMD) probability of fracture of ≥3% for hip and ≥20% for major osteoporotic fracture (MOF).⁽⁷⁾ Proportions are illustrated for the whole cohort (n=4,464), as well as by a prior history of fracture (n=1505) or no prior fracture history (n=2,959).