Greater lumbar spine BMD, bone strength gains with romosozumab for postmenopausal women
Postmenopausal women with osteoporosis receiving romosozumab for 12 months had larger improvements in bone mineral density and bone strength at the lumbar spine compared with those receiving alendronate alone, according to study data.
Data from the ARCH trial showed 1 year of romosozumab-aqqg (Evenity, Amgen) followed by a year of alendronate was associated with larger BMD gains compared with 2 years of alendronate treatment alone. In a substudy of ARCH, romosozumab was also associated with greater gains in integral, cortical and trabecular volumetric BMD and bone mineral content compared with alendronate alone.
“The results of our study are consistent with the greater vertebral fracture risk reduction observed with romosozumab vs. alendronate in the ARCH trial and provide insights into structural determinants of this differential treatment effect,” Jacques P. Brown, MD, a clinical researcher at CHU de Québec Research Centre, Laval University in Canada, told Healio. “The key takeaway from our analysis of data from the ARCH trial is that romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women, and that this improvement is due to the differential treatment effects of romosozumab vs. alendronate on the cortical and trabecular bone compartments of the lumbar spine.”
ARCH is a phase 3, multicenter, randomized, double-blind trial in which postmenopausal women with osteoporosis and a prior fragility fracture were randomly assigned to 210 mg romosozumab monthly or 70 mg oral alendronate weekly for 12 months. At 12 months, all participants received open-label 70 mg oral alendronate weekly for an additional 12 months.
Within the trial, researchers conducted an imaging substudy of 167 participants at study sites with CT availability. Within the substudy, 90 participants underwent quantitative CT/finite element analysis imaging. Areal BMD at the lumbar spine was measured at screening and baseline for all ARCH participants and at months 6 and 18 in the substudy. Quantitative CT scans of the lumbar spine were performed at baseline and months 6, 12 and 24. Outcomes included change from baseline in lumbar spine areal BMD, change from baseline in lumbar spine volumetric BMD and percentage change in lumbar spine vertebral-estimated bone strength by quantitative CT/derived finite element analysis.
The findings were published in The Journal of Bone and Mineral Research.
Greater BMD gains with romosozumab
Of the 90 participants in the substudy’s imaging component, 49 were randomly assigned to romosozumab and 41 to alendronate during ARCH. Participants in the romosozumab group had a 7.8% greater gain in areal BMD at 6 months and 10.3% larger gain at 12 months compared with alendronate (P < .001 for both). The difference continued during the open-label alendronate portion of the study, with the romosozumab group having a 9.6% greater areal BMD gain at both 18 and 24 months compared with alendronate (P < .001 for both).
Romosozumab was associated with a 12% larger gain in integral volumetric BMD at 6 months and a 14.6% larger gain at 12 months compared with alendronate. At 24 months, the romosozumab group had a 13.5% larger gain in integral volumetric BMD compared with alendronate (P < .001 for all). Those taking romosozumab had an 8.9% larger gain in cortical volumetric BMD and a 16.9% larger gain in trabecular volumetric BMD at 6 months compared with alendronate. The gains persisted at 12 and 24 months (P < .001 for all). Participants receiving romosozumab also had a larger absolute bone mineral content gain compared with those receiving alendronate. Most newly formed bone was deposited in the cortical shell compared with the trabecular bone.
Romosozumab increases bone strength
After evaluating lumbar spine bone strength by finite element analysis, the romosozumab group had larger increases in integral, cortical and trabecular bone strength across all time points compared with alendronate. At 24 and 36 months, no participant in the romosozumab group had a confirmed vertebral fracture, whereas two participants in the alendronate group had a confirmed vertebral fracture at 24 months and an additional two women had a confirmed vertebral fracture at 36 months.
“Romosozumab can rapidly improve BMD, bone mineral content and vertebral strength, and therefore is likely to benefit patients at very high risk of fracture,” Brown said. “Further, our findings support recent clinical guidelines that recommend romosozumab as first-line therapy for patients in the very high-risk category for fractures. It is also important to note that romosozumab therapy, which is given for 1 year, should be followed by antiresorptive therapy to preserve BMD gains obtained while on romosozumab; otherwise, discontinuation of romosozumab in the absence of follow-on treatment leads to reversal of the BMD gains.”
Brown added the findings needed to be confirmed in a larger population using fracture endpoints.
For more information:
Jacques P. Brown, MD, can be reached at email@example.com.