Trial results back denosumab as a treatment option for glucocorticoid-induced osteoporosis
medwireNews: Patients with glucocorticoid-induced osteoporosis who are treated with denosumab have greater improvements in bone mineral density than those treated with risedronate, phase III trial results suggest.
“Denosumab could be a useful addition to the treatment armamentarium for glucocorticoid-induced osteoporosis,” write the researchers in The Lancet Diabetes & Endocrinology.
Kenneth Saag (University of Alabama at Birmingham, USA) and co-investigators assessed the efficacy of the RANKL-targeted monoclonal antibody in patients from 79 centers in North and Latin America, Asia, and Europe. Participants had been receiving treatment with glucocorticoids – defined as prednisone at a dose of at least 7.5 mg or equivalent – for at least 3 months (continuing group) or had started taking them within the past 3 months (initiating group).
The majority of patients (68–89%) were receiving glucocorticoid treatment for rheumatologic disorders, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, whereas others had diseases including respiratory disorders and inflammatory bowel disease.
Saag and colleagues found that lumbar spine bone mineral density increased by an average of 4.4% from baseline to the 1-year follow-up among the 209 patients in the glucocorticoid-continuing group who were randomly assigned to receive treatment with oral denosumab 60 mg every 6 months for 2 years, compared with 2.3% for their 211 counterparts treated with oral risedronate 5 mg once daily.
Similarly, in the glucocorticoid-initiating group, lumbar spine bone mineral density increased by an average of 3.8% for the 119 patients given denosumab versus 0.8% for the 126 participants treated with risedronate. The lower bounds of the 95% confidence intervals were above the prespecified noninferiority margins in both the glucocorticoid initiating and continuing groups, indicating that denosumab was noninferior to risedronate, report the researchers.
Moreover, in their analysis of prespecified secondary outcomes, the team found that denosumab was superior to risedronate for improvement of lumbar spine and total hip bone mineral density in both patient groups at the 1-year follow-up.
The incidence of adverse events was comparable between patients treated with denosumab and those given risedronate, with rates of 72% and 69%, respectively. Back pain and arthralgia were the most commonly reported adverse events.
Although the trial results suggest that denosumab is “more efficacious than risedronate for the improvement of bone mineral density, an important predictor of fractures,” Saag and team caution that their study “did not have adequate statistical power to detect fracture differences between treatment groups.”
The authors of an accompanying commentary, Elena Tsourdi (Technische Universität Dresden Medical Center, Germany) and Lorenz Hofbauer (Center for Regenerative Therapies Dresden), agree, noting that “bone mineral density is not the ideal surrogate for trials in patients with glucocorticoid-induced osteoporosis, because it underestimates fracture risk in view of the extraskeletal adverse effects of glucocorticoids on muscle function and falls.”
They also caution that the trial had limited duration of follow-up, and therefore “the question of how long denosumab should be used for is still unanswered.”
Nonetheless, the commentators believe that the results are “an important step towards improved treatment options for glucocorticoid-induced osteoporosis.”
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