Background/Purpose: To compare the actual fracture incidence over 10 years in a longitudinal cohort of patients using glucocorticoids (GCs) with the risk prediction from FRAX (fracture risk assessment tool).

Methods: Adult patients who attended our out-patient rheumatology clinics between 2007 and 2009 who had underlying rheumatic diseases requiring prednisolone treatment (≥5mg/day) and had a DXA scan performed were included. The predicted rates of major osteoporotic and hip fractures were estimated using FRAX (China database) based on the clinical data at the time of DXA, with adjustment when daily dose of prednisolone ≥7.5mg according to the ACR recommendation. The actual observed incidence of symptomatic vertebral and non-vertebral fractures at 10 years (in years 2017-2019) follow-up was retrieved by medical record review and compared with the estimated rates by FRAX. Factors associated with symptomatic clinical fractures at 10 years were studied by logistic regression.

Results: 89 patients were studied (age 49.3±8.8 years at DXA examination; 98% women). The underlying rheumatic diseases were systemic lupus erythematosus (69%), rheumatoid arthritis (17%) and others (14%). The mean daily dose of prednisolone at baseline was 7.7±6.5mg (38% patients had daily dose ≥7.5mg). History of personal fracture was present in 4(4.5%) patients and 22% of female patients had menopause before the age of 45 years. The mean body mass index (BMI) was 23.5±3.3kg/m² (4.5% ≤18kg/m²). Osteoporosis (bone mineral density [BMD] T score ≤-2.5) of the hip, femoral neck and lumbar spine occurred at a frequency of 11.2%, 13.5% and 25.8%, respectively at baseline (32% at any of the 3 sites). 30(34%) patients received anti-osteoporotic treatment (oral bisphosphonates in 25, raloxifene in 3 and denosumab in 2 patients). The estimated mean 10-year risk of major osteoporotic and hip fractures using the BMD data and other risk factors in the FRAX formula, adjusted for prednisolone dose, was 4.3% and 1.0%, respectively. After a follow-up of 10 years, one patient had a hip fracture, 3 patients had humerus fractures and 9 patients had symptomatic vertebral fractures. The actual observed major osteoporotic and hip fracture incidence was 14.6% and 1.1%, respectively (0.146 and 0.011 per 10 patient-years). The observed major clinical fracture rate was significantly higher than that estimated by FRAX (14.6% vs 4.3%; p=0.04). Logistic regression revealed that the only factor independently associated with major clinical fracture at 10 years was BMD T score ≤-2.5 at spine, hip or femoral neck at baseline (OR7.11[1.73-29.2]; p=0.007). Age, prednisolone daily dose, BMI, history of fracture, chronic smoking, having underlying SLE vs not and early menopause were not significantly associated with new clinical fractures.

Conclusion: Despite adjustment for prednisolone dosage, the FRAX formula underestimates the major clinical fracture risk in patients using long-term GCs. The deleterious effect of GCs on bone quality, high proportion of SLE patients, disease activity and use of additional doses of GCs and other immunosuppressive drugs during follow-up are among the contributing factors for this underestimation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/underestimation-of-the-fracture-risk-by-the-frax-formula-in-chronic-glucocorticoid-users-a-10-year-longitudinal-validation-study/