Teriparatide and denosumab may be the most efficacious therapy for prevention of glucocorticoid-induced vertebral fractures, with safety and tolerability profiles similar to those of oral bisphosphonates, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

There are limited data regarding the efficacy and safety of medical treatment for glucocorticoid-induced osteoporosis. Currently, oral bisphosphonates are recommended as first-line agents to prevent glucocorticoid-induced fractures, while intravenous bisphosphonates and subcutaneous teriparatide or denosumab are used as second-line agents.

In the current meta-analysis, the goal was to synthesize evidence and assist in clinical decision making with data regarding the comparative efficacy, tolerability, and safety of the different agents used to prevent glucocorticoid-induced fractures (alendronate, risedronate, ibandronate, zoledronate, teriparatide, and denosumab).

The researchers systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials that lasted ≥12 months and included patients with glucocorticoid-induced osteoporosis or patients who received long-term glucocorticoid treatment (≥3 months). All studies included in the meta-analysis compared an active agent of interest with placebo or another active agent.

Of 746 records identified, the meta-analysis included 22 papers from 19 unique trials that met the study criteria, with a total sample size of 4328 patients receiving long-term glucocorticoid treatment.

There was a significant reduction in risk for vertebral fractures with use of teriparatide (relative risk [RR], 0.11; 95% CI, 0.03-0.47), denosumab (RR, 0.21; 95% CI, 0.09-0.49), and risedronate (RR, 0.33; 95% CI, 0.19-0.58) compared with placebo.

The researchers calculated the surface under the cumulative ranking curve to rank the interventions for each primary outcome. They used estimated values of surface under the cumulative ranking curve to create violin plots for 4 primary outcomes: vertebral fractures, nonvertebral fractures, serious adverse events, and tolerability. Teriparatide and denosumab were judged to be the best interventions in terms of risk reduction for vertebral fractures according to the violin plots.

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Among a subgroup of patients treated with glucocorticoid dosage ≥7.5 mg/d, alendronate (RR, 0.33; 95% CI, 0.12-0.93) and ibandronate (RR, 0.25; 95% CI, 0.06-0.99) were linked with a significant reduction in vertebral fractures compared with placebo. Intravenous ibandronate (RR, 0.25; 95% CI, 0.06-0.99) was efficacious for the primary prevention of glucocorticoid-induced osteoporosis.

The results of the network meta-analysis for the 3 other primary outcomes showed no statistically significant difference for various subgroups. Further, there was no statistically significant difference between the 6 active drugs and placebo in terms of safety and tolerability.

The researchers acknowledged several study limitations, including low to moderate quality evidence in most comparisons, no evidence for the efficacy of zoledronate in reduction of nonvertebral fractures and efficacy of zoledronate and denosumab in reduction of hip fractures, and limited data available on specific adverse events.

“In terms of clinical efficacy and safety, second-line teriparatide and denosumab pose a challenge to first-line oral bisphosphonates for prevention of [glucocorticoid-induced] fractures. Intravenous ibandronate is efficacious for the primary prevention of [glucocorticoid-induced osteoporosis],” concluded the researchers.

“Importantly, to make wise decisions about which drug is optimal for a particular patient, clinicians and patients should incorporate additional considerations such as cost-effectiveness, patient comorbidities, administration route, and drug compliance, apart from clinical efficacy, safety and tolerability,” they wrote.

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Reference

Ding L, Hu J, Wang D, et al. Efficacy and safety of first- and second-line drugs to prevent glucocorticoid-induced fractures: a network meta-analysis [published online September 12, 2019]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz023