SAN DIEGO – The World Health Organization’s widely used, Web-based fracture risk assessment tool known as FRAX seriously underestimates the risk of major osteoporotic and hip fractures in patients with diabetes, according to a large Canadian study.
This finding indicates diabetes is an independent risk factor for fractures above and beyond the conventional risk factors incorporated in the FRAX tool, which include age, gender, smoking, fracture history, and glucocorticoid use – but not diabetes.
Dr. Lora Giangregorio
"One implication of our findings is that FRAX should be applied cautiously in clinical situations involving diabetic patients," Lora Giangregorio, Ph.D., said at the annual meeting of the American Society for Bone and Mineral Research.
"Future iterations of the FRAX tool might consider adding diabetes to the list of risk factors," added Dr. Giangregorio of the University of Waterloo (Ontario).
She presented an analysis of a large Manitoba Province–wide database that included 3,518 patients with type 1 or type 2 diabetes and 36,085 nondiabetic controls, all at least 50 years old when they underwent bone mineral density testing during 1987-2008.
The FRAX tool was used to calculate 10-year fracture risk probabilities, and the actual incidence of major osteoporotic or hip fractures was determined through 2008.
The key finding: After the researchers controlled for FRAX fracture probability scores and the use of osteoporotic medications, diabetes was independently associated with a 59% increased fracture rate during an average 10 years of follow-up.
Of note, despite the increased fracture rate documented in diabetic patients in this study, a lower proportion of subjects with diabetes were receiving osteoporotic medications, compared with the nondiabetes population, Dr. Giangregorio observed.
Diabetes was a stronger predictor of hip fracture risk in younger subjects. Indeed, it was independently associated with a 5.3-fold increased risk of hip fracture in individuals younger than age 65, compared with a 2.1-fold increase in those who were older. In contrast, the risk of major osteoporotic fractures in diabetic patients was not related to age.
The fracture probability curves for diabetic and nondiabetic subjects diverged from the beginning of follow-up and continued to separate throughout the study period.
An important area for future research, in Dr. Giangregorio’s view, is the identification of potentially modifiable diabetes-related fracture risk factors. As a hypothetical example, perhaps some diabetes medications are associated with an increase in fractures while others are not.
"Future iterations of the FRAX tool might consider adding diabetes to the list of risk factors."
The study did not differentiate between type 1 and type 2 diabetes. However, in another study presented at the meeting, Dr. Ling Oei of Erasmus University, Rotterdam, the Netherlands, noted that patients with type 2 diabetes are paradoxically at increased risk of osteoporotic fractures even though their bone mineral density is typically normal or even increased.
In a prospective, population-based study of 203 patients with adequately controlled type 2 diabetes, 217 others with inadequately controlled disease, and 3,715 nondiabetic controls, Dr. Oei and coworkers showed that women with inadequately controlled diabetes had significantly higher bone mineral density at both the lumbar spine and femoral neck, compared with women in the other two groups.
After the researchers controlled for age, femoral neck bone mineral density, and body mass index, women with inadequately controlled type 2 diabetes had a 1.6-fold increased risk of fracture during an average 8.2-year follow-up, compared with patients who had adequately controlled type 2 diabetes or patients without diabetes. In other words, inadequate control of type 2 diabetes appears to be a risk factor for fracture in elderly women but not men, according to the Dutch investigators.
Dr. Giangregorio and Dr. Oei reported having no financial conflicts.