Predictors of Imminent Risk of Nonvertebral Fracture in Older, High‐Risk Women: The Framingham Osteoporosis Study

Abstract

Osteoporosis treatment decisions are often based solely on BMD or on 10‐year fracture risk; little is known about factors increasing imminent fracture risk. Understanding factors contributing to imminent risk of fracture is potentially useful for personalizing therapy, especially among those at high risk. Our aim was to identify predictors of nonvertebral fracture for 1‐ and 2‐year periods in women at high risk for fracture. The Framingham Osteoporosis Study cohort included 1470 women (contributing 2778 observations), aged ≥65 years with BMD hip T ‐score ≤ −1.0, or history of fragility fracture (irrespective of T ‐score). Nonvertebral fractures were ascertained prospectively over 1 year and 2 years following a baseline BMD scan. Potential risk factors included age, anthropometric variables, comorbidities/medical history, cognitive function, medications, history of fracture, self‐rated health, falls in the past year, smoking, physical performance, hip BMD T ‐score, Activities of Daily Living (ADL) score, and caffeine and alcohol intakes. Predictive factors with p value ≤ 0.10 in bivariate Cox proportional hazards regression models were subsequently considered in multivariable models. Mean baseline age was 75 years (SD 6.0). During 1‐year follow‐up, 89 nonvertebral fractures occurred; during 2‐year follow‐up, 176 fractures occurred. Of the variables considered in the bivariate models, significant predictors of nonvertebral fractures included age, history of fracture, self‐rated health, falls in the prior year, BMD T ‐score, ADL, renal disease, dementia, and current use of nitrates, beta‐blockers, calcium channel blockers, or antidepressants. In multivariable models, significant independent risk factors were history of fracture, self‐rated health, hip BMD T ‐score, and use of nitrates. Significant 1‐year results were attenuated at the 2‐year follow‐up. In addition to the traditional factors of BMD and fracture history, self‐rated health and use of nitrates were independently associated with imminent risk of fracture in older, high‐risk women. These specific risk factors thus may be useful in identifying which women to target for therapy. ©2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Determinants of imminent fracture risk in postmenopausal women with osteoporosis

“…Our models show that most of the predictors of imminent risk include characteristics that reflect health status, which is likely to change over time, particularly in older individuals. This is consistent with a growing body of literature suggesting that an individual's fracture risk is dynamic, in that it varies over time and may be dependent on the specific combinations of risk factors that are present [18,[23][24][25][26][27]. Given that health status changes and medical events (e.g., myocardial infarction, stroke, Alzheimer's diagnosis) that affect factors such as physical functioning occur more frequently with increasing age, annual assessments of fracture risk would likely help better identify those patients most at imminent risk of fracture and support improved management of fracture risk in these patients [18,23,27].…”

“…While there is no broadly accepted definition of imminent fracture risk, we chose to focus on factors predicting fracture in the next year to add to the literature on assessing risk over a shorter time frame, in contrast to the traditional longer-term fracture risk prediction framework. Our findings align well with the growing body of literature on imminent risk of fracture, including observational studies which have consistently identified low BMD, prior fractures, age, poor health status, previous falls, specific comorbidities that influence physical and cognitive functioning (both of which are risk factors for falls), as well as other fall-related risk factors, as key predictors of the imminent risk of fracture [18,[23][24][25][26][27][28].…”

Grip strength in men and women aged 50–79 years is associated with non-vertebral osteoporotic fracture during 15 years follow-up: The Tromsø Study 1994–1995

“…Thus, we may postulate that part of the association between grip strength and fracture goes through BMD. The same may be the case for physical limitations and low self-perceived health which both have shown to be associated with hip fractures [42]. Low BMI is a wellknown risk factor for hip fracture.…”

Defining Very High Fracture Risk: Is FRAX Fit for Purpose?

“…( 12 ) Across these and other studies, factors other than recent fracture that have been reported to increase imminent risk include comorbidities, glucocorticoid therapy, falls, greater age, and lower bone mineral density (BMD). ( 13–15 ) Collectively, these data provide a strong rationale for early intervention after incident fracture, particularly that which has occurred at the spine or hip. In such individuals, skeletal anabolic therapy should be strongly considered in view of the evidence for greater and more rapid reduction in fracture risk when compared with antiresorptive drugs.…”