Romosozumab improves bone health in osteoporotic women with diabetes

Treatment with romosozumab for 12 months, followed by 24 months of alendronate, results in significant improvements in lumbar spine areal bone mineral density (BMD) and tissue thickness-adjusted trabecular bone score (TBS) algorithm (TBSTT) compared with alendronate alone among postmenopausal women with osteoporosis and type 2 diabetes (T2D), reports a study.

"These changes may reflect a greater improvement in bone strength observed with romosozumab vs alendronate in patients with T2D,” the researchers said.

 A post hoc analysis was performed on women from the ARCH study who had T2D and lumbar spine DXA scans at baseline and ≥1 postbaseline visit (romosozumab-to-alendronate, n=165; alendronate-to-alendronate, n=195).

The research team assessed areal BMD and TBS (determined by an updated TBSTT) on lumbar spine DXA scans at baseline and ≥1 postbaseline visit (months 12, 24, and 36).

Treatment with romosozumab resulted in significantly greater improvements in lumbar spine areal BMD and TBSTT at month 12 relative to alendronate alone. These gains were sustained following the transition to alendronate and significantly persisted at months 24 and 36 vs alendronate monotherapy. [J Clin Endocrinol Metab 2025;110:2861-2868]

TBSTT percentage changes showed a weak association with lumbar spine areal BMD percentage changes from baseline to month 36 (romosozumab-to-alendronate, R2=0.1493; alendronate-to-alendronate, R2=0.0429).

“Our results indicate that the subgroup of patients with T2D in the ARCH study responded to romosozumab with larger increases in lumbar spine BMD and TBSTT with alendronate, with the TBSTT results similar to those observed for a subpopulation of patients in ARCH mainly without diabetes,” the researchers said. [J Bone Miner Res 2024:zjae194] 

“As in the overall population of the ARCH study, patients with diabetes treated with romosozumab responded with larger increases in lumbar spine BMD compared with patients treated with alendronate,” they added. [N Engl J Med 2017;377:1417‐1427] 

These findings support those from the imaging substudy of ARCH, which showed a larger increase in bone strength for a given absolute change in integral volumetric BMD for the romosozumab-to-alendronate group vs the alendronate-to-alendronate group.

This suggested that the change in vertebral bone strength may come from the gains in areal BMD as well as improvements in BMD distribution or bone microarchitecture, according to the researchers.

TBSTT changes

“Our analysis confirmed that changes in TBSTT were largely independent of the percentage change in lumbar spine areal BMD over 12, 24, or 36 months of treatment, with either romosozumab-to-alendronate or alendronate-to-alendronate,” the researchers said. 

The correlation coefficients in the two groups were comparable to those reported with TBSTT for romosozumab, alendronate, and other treatments for osteoporosis in nondiabetic populations. [J Bone Miner Res 2024:zjae194; Osteoporos Int 2022;33:2517‐2525]

“We are not aware of published TBSTT thresholds, so to evaluate the effect of romosozumab on achieving normal lumbar spine TBSTT, we derived the TBSTT thresholds from the tertile analysis of the same study population from an individual-level meta-analysis as described for the derivation of TBS thresholds by McCloskey [and colleagues],” the researchers said. [J Bone Miner Res 2016;31:940‐948]

"Similarly, individual-level meta-analysis data from large populations could be used to establish TBSTT thresholds for use across studies,” they added.