Glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis. Glucocorticoid exposure is closely associated with osteoporosis, and 35% of patients who receive chronic treatment with glucocorticoids go on to have vertebral fractures. These patients require both primary and secondary fracture prevention. Although the bisphosphonate risedronate is frequently prescribed to treat glucocorticoid-induced osteoporosis, many patients never receive preventive treatment. Several randomized clinical trials have evaluated different therapies for glucocorticoid-induced osteoporosis. These treatments include alendronate, risedronate, zoledronic acid and teriparatide, all of which appear to be effective at maintaining or increasing bone mass.
A recent study identified the RANKL inhibitor denosumab as another useful treatment option for patients newly initiating or continuing glucocorticoid therapy who are at increased risk for fractures. Kenneth G. Saag, MD, professor at the University of Alabama, Birmingham, published the 12-month results of the 24-month randomized, active-controlled trial online April 6 in Lancet Diabetes Endocrinology.1 The study is one of the largest, randomized, controlled trials on glucocorticoid-induced osteoporosis and the first large, randomized, controlled trial of denosumab in patients with glucocorticoid-induced osteoporosis who were either prevalent glucocorticoid users or newly initiating glucocorticoid therapy.
“We chose risedronate as the active comparator for three reasons,” explain the authors in their discussion. “First, our study was modeled on a study of zoledronic acid for treatment and prevention of glucocorticoid-induced osteoporosis, in which risedronate was the active comparator. Second, the non-inferiority margin for an active-controlled study is best derived from the treatment effect of the chosen active control in a placebo-controlled study in the same population of interest, and such data were available for risedronate. Finally, risedronate was approved and available in all countries participating in this global study.”
Of the 795 patients in the study, 505 were continuing glucocorticoid treatment and 290 were initiating glucocorticoid treatment. The patients were enrolled in 79 centers worldwide and randomly assigned to receive treatment with either denosumab or risedronate. The investigators found that denosumab was both non-inferior and superior to risedronate in patients already taking or newly initiating glucocorticoid therapy. Specifically, denosumab was more effective than risedronate for the improvement of bone mineral density at the lumbar spine in this patient population. Moreover, denosumab and risedronate had clinical effects similar to those documented in previous osteoporosis studies. Although the study included 795 patients, it was not powered to detect fracture differences between the treatment groups.
Patients in the two treatment groups had similar safety profiles, suggesting denosumab is well tolerated. The most common adverse events in both treatment groups were back pain and arthralgia. Previous studies found patients treated with denosumab were more likely to experience serious skin infections and a higher rate of urinary tract infections than placebo-treated patients. However, the current study found the incidence of serious adverse events, including serious infections and fractures, was similar between the groups at about 4%.