General Comorbidity Indicators Contribute to Fracture Risk Independent of FRAX: Registry-Based Cohort Study

Context: FRAX® estimates 10-year fracture probability from osteoporosis-specific risk factors. Medical comorbidity indicators are associated with fracture risk but whether these are independent from those in FRAX is uncertain.

Objective: We hypothesized Johns Hopkins Aggregated Diagnosis Groups (ADG®) score or recent hospitalization number may be independently associated with increased risk for fractures.

Methods: This retrospective cohort study included women and men age ≥ 40 in the Manitoba BMD Registry (1996-2016) with at least 3 years prior health care data and used linked administrative databases to construct ADG scores along with number of hospitalizations for each individual. Incident Major Osteoporotic Fracture and Hip Fracture was ascertained during average follow-up of 9 years; Cox regression analysis determined the association between increasing ADG score or number of hospitalizations and fractures.

Results: Separately, hospitalizations and ADG score independently increased the hazard ratio for fracture at all levels of comorbidity (hazard range 1.2-1.8, all P < 0.05), irrespective of adjustment for FRAX, BMD, and competing mortality. Taken together, there was still a higher than predicted rate of fracture at all levels of increased comorbidity, independent of FRAX and BMD but attenuated by competing mortality. Using an intervention threshold of major fracture risk >20%, application of the comorbidity hazard ratio multiplier to the patient population FRAX scores would increase the number of treatment candidates from 8.6% to 14.4%.

Conclusion: Both complex and simple measures of medical comorbidity may be used to modify FRAX-based risk estimates to capture the increased fracture risk associated with multiple comorbid conditions in older patients.