Denosumab beats risedronate for glucocorticoid-induced osteoporosis
Denosumab appears to be a more attractive treatment option for glucocorticoid-induced osteoporosis compared with risedronate, with the former yielding superior improvements in spine and hip bone mineral density (BMD) through 2 years and having a similar safety profile, according to a study.
“This final analysis of a 24-month, prospective, randomized, double-blind, double-dummy [phase III] trial provided additional evidence of the efficacy and safety of denosumab, compared with risedronate, an established therapy, in glucocorticoid-treated individuals at high risk of fracture,” the investigators said.
The analysis included 590 adults randomized to treatment with either subcutaneous denosumab at 60 mg every 6 months or risedronate 5 mg orally once daily for 24 months, in addition to daily calcium and vitamin D. All participants had been receiving ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid‐initiating; denosumab, n=109; risedronate, n=117) or ≥3 months (glucocorticoid‐continuing; denosumab, n=186; risedronate, n=178) before study entry.
“The superior effect of denosumab vs risedronate on spine and hip BMD that was observed in the primary analysis at month 12 continued through month 24 in each subpopulation,” the investigators noted. [Lancet Diabetes Endocrinol 2018;6:445-454]
Compared with risedronate, denosumab produced superior increases in BMD at 24 months from baseline both in the glucocorticoid‐initiating (lumbar spine: 6.2 percent vs 1.7 percent; total hip: 3.1 percent vs 0.0 percent; p<0.001) and glucocorticoid‐continuing subgroups (lumbar spine: 6.4 percent vs 3.2 percent; total hip: 2.9 percent vs 0.5 percent; p<0.001). [Arthritis Rheumatol 2019;doi:10.1002/art.40874]
Results were similar for BMD at the femoral neck and 1/3 radius, with significantly greater improvements seen with denosumab vs risedronate in each subgroup.
“The treatment difference for BMD at each skeletal site was larger at month 24 than at month 12, reflecting the progressive increase for most measures of BMD in the denosumab group vs the plateau in the risedronate group beyond 12 months, which has also been shown in other studies,” the investigators pointed out. [Osteoporos Int 2012;23:1769-1778; J Bone Miner Res 2012;27:243-254]
Reductions in bone turnover markers, while markedly greater with denosumab through month 12, did not significantly differ between the treatment groups at month 24.
Adverse events, serious adverse events (including infections) and fractures were similar in the two treatment groups and consistent with the results of the primary analysis at month 12.
Overall, findings of the present trial suggest that denosumab may represent a new treatment option for at least 24 months to patients with glucocorticoid-induced osteoporosis, according to the investigators.
“A potential limitation of this study was that it was neither designed nor powered to evaluate fracture as an efficacy endpoint; fracture data were collected as a safety endpoint. However, it would be difficult to show efficacy for fracture prevention in this setting due to the very large number of [participants] that would be required to show superiority with respect to a fracture endpoint,” they said.
Moreover, denosumab was evaluated against only one drug—risedronate. “Thus, how denosumab compares with other bisphosphonates or other bone-specific agents is unknown,” they added.