Guidance for the adjustment of FRAX according to the dose of glucocorticoids

We examined the effect of glucocorticoid dose on FRAXA (R) derived fracture probabilities in a UK setting. A relatively simple adjustment of conventional FRAX estimates of probabilities of hip fracture and a major osteoporotic fracture can be applied to modulate the risk assessment with knowledge of the dose of glucocorticoids. The WHO fracture risk assessment (FRAX) tool estimates 10-year probability of fracture based upon multiple clinical risk factors and an optional femoral neck BMD measurement. Ever (past and current) use of systemic glucocorticoids is a dichotomous risk factor (yes/no) and does not therefore take account of the dose of glucocorticoids. The aim of this work was to estimate the adjustment for fracture probability based upon the dose of glucocorticoids. Dose responses for fracture risk during exposure to glucocorticoids were taken from the General Practice Research Database and used to adjust the relative risks for glucocorticoids in FRAX. In addition to fracture risk, a dose response for the death hazard was estimated and both variables were used to populate the FRAX model for the UK. The exposure to glucocorticoids was found to significantly affect fracture probability. The following rule was formulated. For low-dose exposure (< 2.5 mg daily of prednisolone or equivalent), the probability of a major fracture is decreased by about 20% depending on age. For medium doses (2.5-7.5 mg daily), the unadjusted FRAX value can be used. For high doses (> 7.5 mg daily), probabilities can be upward revised by about 15%. Conversion factors were also determined for the adjustment of hip fracture probability. A relatively simple adjustment of conventional FRAX estimates of probabilities of hip fracture and a major osteoporotic fracture can be applied to modulate the risk assessment with knowledge of the dose of glucocorticoids.