Fracture risk with intermittent high‐dose oral glucocorticoid therapy

Abstract

Objective. To evaluate the risk of fracture in patients receiving intermittent therapy with high-dose oral glucocorticoids (GCs).Methods. The study group comprised 191,752 patients from the UK General Practice Database who were 40 years of age and older and received therapy with GCs. The followup time period was divided into the categories of "current" and "no exposure." The daily dose and cumulative dose for each time period were determined. Relative risks were estimated using Cox proportional hazards models, adjusted for age, sex, body mass index, smoking, disease history, and drug history. Fractures of the radius/ulna, humerus, rib, femur/hip, pelvis, or vertebrae were included in the evaluation.Results. Patients who intermittently received high-dose GCs (daily dose >15 mg) and had no or little previous exposure to GCs (cumulative exposure <1 gm) had a small increased risk of osteoporotic (but not hip/femur) fracture; this risk increased substantially with increasing cumulative exposure. Among patients who received a daily dose >30 mg and whose cumulative exposure was >5 gm, the relative risk (RR) of osteoporotic fracture was 3.63 (95% confidence interval [95% CI] 2.54-5.20), the RR of fracture of the hip/femur was 3.13 (95% CI 1.49-6.59), and the RR of vertebral fracture was 14.42 (95% CI 8.29-25.08).Conclusion. Intermittent use of high-dose oral GCs (daily dose >15 mg and cumulative exposure <1 gm) may result in a small increased risk of osteoporotic fracture. Conversely, patients who receive several courses of high-dose GCs (daily dose >15 mg and cumulative exposure >1 gm) have a substantially increased risk of fracture.

Incidence of Symptomatic Vertebral Fracture with Highdose Glucocorticoid Treatment in the Chiba-Shimoshizu Rheumatic Cohort between 1986 and 2006

“…in the present study, both the higher initial dose and the greater numbers of gc dose-increase were two independent risk factors. The increased fracture risk with intermittent high-dose oral gc therapy was recently demonstrated by others [33], indicating that the exposure to high gc dose during a long period of time might produce the bone damage. however, the very high gc dose with a short period of exposure may not be what induces the damage, since gc pulse therapy was not correlated to bone fracture.…”

Prevention of glucocorticoid‐induced bone loss in mice by inhibition of RANKL

“…In fact, recent studies showed that the relative risk (RR) of clinical vertebral fracture in patients receiving oral glucocorticoid therapy was 2.6 and, thus, much greater than that for hip fractures (RR 1.6) or nonvertebral fractures (RR 1.3) (31,32). Moreover, fractures in glucocorticoid-induced osteoporosis occur at thresholds of BMD (T score of Ϫ1.5) that are above those of postmenopausal osteoporosis (31,32). Consistent with the clinical data, prednisolone treatment of hRANKL-knockin mice predominantly caused loss of bone mass and bone strength at the spine.…”

A review of lifestyle, smoking and other modifiable risk factors for osteoporotic fractures

“…Osteoporosis is a familiar adverse effect of a few classes of drugs, including glucocorticoids 71,72 and aromatase inhibitors, 73 and a strongly suspected adverse effect with others, such as proton pump inhibitors (PPIs) or SSRIs. Although the drugs may have been prescribed for the best of clinical reasons, there may be a potential for risk modification by successfully controlling diseases with drugs that are not harmful to the skeleton (for example, using H2 blockers instead of PPIs where possible) or by modifying risk by co-administration of osteoporosis drugs.…”