The Comparative Efficacy of 12-months of Alendronate and Raloxifene in Maintaining Denosumab-Induced Improvement in Peripheral Volumetric Bone Mineral Density, Microarchitecture and Estimated Strength

When denosumab is discontinued, antiresorptive therapy is necessary to mitigate high bone turnover bone loss. While bisphosphonates have been investigated for this, alternatives have received less attention. In the CARD randomized, controlled, open-label study, we previously reported alendronate better suppressed bone remodeling and maintained denosumab-induced areal bone mineral density (aBMD) gains than raloxifene, though raloxifene maintained femoral neck aBMD and partially inhibited loss elsewhere. In this exploratory analysis, we now assess the comparative ability of these drugs to maintain denosumab-induced improvements in peripheral volumetric BMD (vBMD), microarchitecture, and estimated bone strength. CARD randomized 51 postmenopausal women (60-81yo) at high fracture risk to receive denosumab 60-mg by subcutaneous injection every 6 mo for 12-mo followed by either 12-mo of oral alendronate (70 mg weekly, n = 26) or oral raloxifene (60 mg daily, n = 25). Total, trabecular, and cortical vBMD and skeletal microarchitecture were measured by high-resolution peripheral quantitative CT of the distal radius and distal tibia. After 12-mo of denosumab, mean total and cortical vBMD at the radius and tibia increased significantly in the cohort as a whole, whereas trabecular vBMD did not change significantly. Bone strength (stiffness and failure load as estimated by finite element analysis) also increased significantly at both sites. After the transition to alternate antiresorptive therapy, the gains observed in total and compartmental vBMD and estimated bone strength were maintained in both treatment groups with no significant between-group differences. No significant changes in cortical porosity or thickness were observed either during denosumab treatment nor after the transition to alternate antiresorptive therapy. We conclude that denosumab improved vBMD and bone strength, and these gains were maintained with both alendronate or raloxifene, supporting raloxifene as an option for those unable or unwilling to take bisphosphonates after short-term denosumab exposure.